Original Article
The Agent of Bacillary Angiomatosis — An Approach to the Identification of Uncultured Pathogens
N Engl J Med 1990; 323:1573-1580December 6, 1990
- Abstract
- Abstract
Background.
Bacillary angiomatosis is an infectious disease causing proliferation of small blood vessels in the skin and visceral organs of patients with human immunodeficiency virus infection and other immunocompromised hosts. The agent is often visualized in tissue sections of lesions with Warthin—Starry staining, but the bacillus has not been successfully cultured or identified. This bacillus may also cause cat scratch disease.
Methods.
In attempting to identify this organism, we used the polymerase chain reaction. We used oligonucleotide primers complementary to the 16S ribosomal RNA genes of eubacteria to amplify 16S ribosomal gene fragments directly from tissue samples of bacillary angiomatosis. The DNA sequence of these fragments was determined and analyzed for phylogenetic relatedness to other known organisms. Normal tissues were studied in parallel.
Results.
Tissue from three unrelated patients with bacillary angiomatosis yielded a unique 16S gene sequence. A sequence obtained from a fourth patient with bacillary angiomatosis differed from the sequence found in the other three patients at only 4 of 241 base positions. No related 16S gene fragment was detected in the normal tissues. These 16S sequences associated with bacillary angiomatosis belong to a previously uncharacterized microorganism, most closely related to Rochalimaea quintana.
Conclusions.
The cause of bacillary angiomatosis is a previously uncharacterized rickettsia-like organism, closely related to R. quintana. This method for the identification of an uncultured pathogen may be applicable to other infectious diseases of unknown cause. (N Engl J Med 1990; 323:1573–80.)
Article Activity
- Article
BACILLARY angiomatosis (also called epithelioid angiomatosis) and cat scratch disease are important clinical disorders that are presumed to be infectious on the basis of direct visualization of microorganisms in diseased tissues. Because these organisms cannot be grown reproducibly, the identity of the presumed pathogen or pathogens remains unknown.
Bacillary angiomatosis is a distinct vascular proliferative disease initially described in the skin and lymph nodes of patients seropositive for the human immunodeficiency virus (HIV).1 , 2 Lesions from this disorder have been found to contain clusters of bacilli with positive results on Warthin—Starry staining that resemble those found in cat scratch disease,3 , 4 although the histologic appearance of the disease differs from that of classic cat scratch disease.5 Bacillary angiomatosis is known to cause disseminated visceral disease in HIV-seropositive patients and other immunocompromised hosts,6 7 8 and it has recently been found to do so in an immunocompetent host.9 Cat scratch disease is usually a benign granulomatous disease involving skin and regional lymph nodes10 , 11; however, disseminated disease has been described that involves visceral organs, particularly in immunocompromised hosts.12 13 14 The causative agent of cat scratch disease was first visualized in 1983 with the Warthin—Starry silver stain15 but has resisted identification despite reports of isolation in culture.16 Distinguishing between disseminated bacillary angiomatosis and cat scratch disease in the immunocompromised host is difficult17; the ability to identify the causative bacteria would help resolve this difficulty as well as improve diagnosis and treatment and perhaps lead to a better understanding of pathogenesis.
Two recent experimental developments — analysis of 16S ribosomal RNA (rRNA)18 , 19 and the polymerase chain reaction (PCR)20 21 22 — have allowed a novel approach to the identification of disease-associated, uncultured microorganisms. All cells contain multiple copies of a gene encoding a 16S or 16S-like small subunit of rRNA, in which hypervariable sequences are interspersed with regions of highly conserved sequence.19 The analysis of the variable portions permits the determination of phylogenetic and evolutionary relations among organisms and now forms the basis of a revised system of natural classification.19 Sequences conserved throughout each or all three kingdoms (eukaryotes, archaeobacteria, and eubacteria) can serve as targets for primer-directed DNA amplification or hybridization.23
The PCR can be used to amplify a 16S-like eukaryotic rRNA sequence from purified genomic DNA.24 It permits rapid amplification of any DNA region of interest if the sequences flanking the segment of interest are known, so that two amplification primers can be designed, and if there is an appropriate pool of DNA containing the target region.21 , 25 Therefore, one might be able to identify an unknown eubacterium with primer-directed, amplified variable regions of its 16S rRNA sequence by using primers that anneal to flanking sequences conserved within the kingdom of eubacteria.26 Although pure cultured organisms have usually been the source of the 16S ribosomal DNA (rDNA) target in PCR, infected human tissue could also be used.
A recent case of disseminated bacillary angiomatosis at our institution8 provided us with the appropriate target DNA needed for the execution of this strategy. Using broad-range eubacterial 16S rDNA primers, we amplified, cloned, and sequenced a portion of eubacterial 16S rRNA gene directly from tissue infected with the presumed etiologic agent. Subsequent analysis of this sequence and study of infected tissues from other patients suggest that bacillary angiomatosis is caused by a rickettsia-like organism that is most closely related to Rochalimaea quintana.
Methods
Patients
Patient 1 was a 38-year-old woman in whom fever, chills, headache, myalgias, nausea, and vomiting developed five years after cardiac transplantation while she was following a maintenance regimen of immunosuppressive drugs.8 Three months earlier she had required surgical repair of a cat scratch. Abdominal CT scanning revealed hepatosplenomegaly with multiple areas of low attenuation and surrounding enhancement. Exploratory laparotomy and splenectomy were performed. Histologic examination of liver, spleen, and splenic hilar lymph node demonstrated a proliferation of histiocytoid endothelial cells forming vascular channels. Numerous bacillary organisms were seen on Warthin—Starry staining and electron microscopy (Fig. 1Figure 1
Splenic Nodule from Patient 1 after Warthin—Starry Staining.). Routine bacterial cultures were negative. A diagnosis of bacillary angiomatosis was made. The patient was treated with an eight-week course of erythromycin, with complete resolution of her symptoms.Patient 2 was a 24-year-old HIV-seropositive man who had a two-month history of fever, chills, sweating, abdominal pain, anorexia, and weight loss.8 He had had several cat scratches in the previous three months. Physical examination revealed a 1.0-cm purplish nodule on his left elbow, left-axillary lymphadenopathy, and hepatosplenomegaly. A skin biopsy, bone marrow aspiration and biopsy, and core liver biopsy were performed. Pathological examination of the skin was suggestive of pyogenic granuloma; however, Warthin—Starry staining revealed bacillary organisms. Sections of bone marrow showed focal areas of epithelioid angiomatosis, but there was insufficient material for Warthin—Starry staining. Histologic findings in the liver were consistent with epithelioid angiomatosis, with Warthin—Starry staining positive for bacillary organisms. All cultures were negative. Treatment with doxycycline led to prompt clinical improvement.
Patient 3 was a 54-year-old woman infected with HIV. A biopsy of a cutaneous heel lesion was performed, and Warthin—Starry staining demonstrated clumps of bacilli. Histologic findings suggested a diagnosis of bacillary angiomatosis. (This case has been described elsewhere by LeBoit et al. [Case 8].5)
Patient 4 was a 29-year-old woman with the acquired immunodeficiency syndrome in whom diffuse lymphadenopathy developed. She had no skin lesions. Biopsy of an inguinal lymph node showed histologic features consistent with epithelioid angiomatosis. Clusters of bacilli were seen on Warthin—Starry staining.
DNA Extraction
DNA was extracted from a frozen splenic nodule and a frozen piece of splenic hilar lymph node from Patient 1, a frozen sample of bone marrow from Patient 2, paraffin-embedded, formalin-fixed tissue from a skin lesion from Patient 3, and a paraffin-embedded, formalin-fixed lymph node from Patient 4. Each of these patients had the biopsy performed at a different hospital. As a control for DNA carryover contamination, for every biopsy sample from the patients we prepared DNA extracts from at least one of the following tissues: frozen spleen from a patient with idiopathic thrombocytopenic purpura, with no clinical or cultural evidence of infection; a paraffin-embedded, formalin-fixed spleen sample obtained by splenectomy in a trauma victim; and frozen tonsil from two patients with recurrent tonsillitis.
Frozen Tissue
The methods used were modified from those described previously.27 , 28 Approximately 100 mg of each tissue was rinsed in sterile water, minced, and placed in 5 ml of digestion buffer (500 mM TRIS, pH 9; 20 mM EDTA; 10 mM sodium chloride; and 1 percent sodium dodecyl sulfate) with fresh proteinase K (Sigma, St. Louis) at a final concentration of 1 mg per milliliter. The samples were incubated at 60°C for 48 to 72 hours. Ribonuclease A (Sigma) was added to a final concentration of 4 μg per milliliter; the samples were incubated at room temperature for two hours and then extracted three times with equal volumes of TRIS-buffered phenol and chloroform—isoamyl alcohol (24:1). The DNA was precipitated with ethanol according to standard techniques29 and resuspended in 50 μl of sterile water.
Paraffin-Embedded Tissue
The method used was a modification of that published by Shibata et al.30 and described by Wright and Manos.31 Ten-micrometer sections from the various paraffin-embedded blocks of tissue were trimmed, treated with octane and ethanol, and then placed in 200 μl of digestion buffer as described.31 After digestion and heat inactivation of proteinase K, the reaction mixture was centrifuged and the supernatant was used directly in amplification reactions.
Oligonucleotide Primers
The sequences of primers p11E and p13B were adapted with modifications from Chen et al.26 Primers p93E, p24E, and p12B were designed on the basis of the 16S rRNA sequence determined in this study (Table 1Table 1
Oligonucleotide Primers Used for Amplification of 16S rDNA.*). Each included either an EcoRI or BamHI restriction-endonuclease site at the 5′ end to facilitate the cloning of the resultant PCR product. All primers were synthesized by Operon Technologies (Alameda, Calif.).PCR Amplification
DNA extracts from frozen tissue were adjusted to a concentration of approximately 400 to 500 μg of total DNA per milliliter; 1 μl was used in a 100-μl reaction volume. Ten microliters (5 percent) of the paraffin-embedded DNA extract was sufficient for the amplification of human β-globin genes with primers PC04 and GH20 (Perkin–Elmer–Cetus, Norwalk, Conn.); the same amount was used for the amplification of eubacterial 16S rRNA. Each reaction contained 20 pmol of each primer and standard amounts of Gene-Amp reagents (Perkin–Elmer–Cetus), except that 2 mM magnesium chloride was used for amplification with extracts of paraffin-embedded tissue. This mixture was irradiated with ultraviolet light to reduce contamination of reagents. An overlay of sterile mineral oil was added to the tubes, followed by the DNA template. PCR cycles consisted of 1 minute of denaturation at 94°C, 1 minute of annealing at 55°C, and 1.5 minutes of extension at 72°C in a programmable thermal controller (MJ Research, Watertown, Mass.). For amplification with extracts of paraffin-embedded tissue, we used a step file in an automated DNA thermal cycler (Perkin–Elmer–Cetus). Negative controls were included during every amplification and consisted of reaction mixtures without the DNA template, as well as reaction mixtures with DNA extracts from nondiseased tissues. The product of PCR was detected by electrophoresing 10 μl of reaction solution in a 1.2 percent agarose gel containing ethidium bromide; a 1-kilobase (kb) DNA ladder (GIBCO BRL, Gaithersburg, Md.) was used as the DNA size standard on each gel.
Purification, Cloning, and Sequencing of the PCR Product
Half the PCR product was extracted with phenol and chloroform, precipitated with ethanol, and pelleted. The 3′ ends of DNA strands were filled in with DNA polymerase I large (Klenow) fragment.29 The product was purified by low-melting-point agarose-gel electrophoresis, cut with a combination of EcoRI and BamHI (New England Biolabs, Beverly, Mass.), and then ligated with pBluescript II KS phagemid vector (Stratagene, La Jolla, Calif.), which had been cut with EcoRI and BamHI.29 Escherichia coli DH5α (Bethesda Research Laboratories, Bethesda, Md.) was electro-transformed32 with the recombinant plasmids with a Bio-Rad gene pulser (Richmond, Calif.). After screening of the ampicillin-resistant transformants for the appropriate recombinant plasmid, both strands of the plasmid inserts were sequenced with double-stranded DNA templates (Sequenase; U.S. Biochemical, Cleveland) and the dideoxy chain-termination method.33
Data Analysis
Sequences were aligned manually on the basis of conserved regions and secondary structural elements. Regions of ambiguous alignment were omitted from the phylogenetic analysis. The evolutionary distance separating two sequences was computed from the percent similarities34; a least-squares method was used to infer the phylogenetic tree most consistent with the calculated distance.35 All reference 16S rRNA sequences were obtained from the GenBank (Los Alamos, N.M.)/European Molecular Biology Laboratory (Heidelberg, Germany) data bases.
Results
Amplification of 16S rRNA Sequence from Tissue Extract Using Broad-Range Eubacterial Primers
Frozen splenic tissue from Patient 1 was chosen as the initial target for 16S rRNA amplification because of the relatively large number of bacteria seen with Warthin—Starry staining (Fig. 1B). Eubacterial broad-range primers p22E and p13B were designed from 16S rDNA gene sequences known to be conserved in all eubacteria26 but not found in eukaryotic 16S-like genes. Previous studies have demonstrated that picogram amounts of E. coli 16S rDNA could be detected with the use of these primers as hybridization probes in the presence of a large excess of eukaryotic genomic DNA.26
After 25 cycles of PCR amplification using p11E and p13B and splenic or splenic hilar lymph-node DNA from Patient 1 as the target, a product of approximately 200 base pairs (bp) was detected reproducibly with agarose-gel electrophoresis (Fig. 2Figure 2
Agarose-Gel Electrophoresis of PCR-Amplified 16S rDNA Fragments from Tissue DNA Extracts., lanes 4 and 5). No DNA band could be amplified from the spleen sample from a patient with idiopathic thrombocytopenic purpura or in the absence of added tissue extract (Fig. 2, lanes 2 and 1, respectively). With DNA from "normal" human tonsillar tissue, a DNA species of similar size was sometimes barely seen although not easily reproduced (Fig. 2, lane 3). This might be expected since such tissue was obtained from a site contaminated with normal mucosal flora. After 35 or more cycles of PCR amplification with p11E and p13B, faint bands could sometimes be seen in all reaction mixtures.Sequence Determination and Development of Specific Primers
The DNA fragment amplified from the splenic extract from Patient 1 was purified, cloned, and then sequenced. Comparison of this sequence with all known DNA sequences in the GenBank/European Molecular Biology Laboratory data libraries showed that this 232-bp fragment could readily be aligned with eubacterial 16S rRNA genes but was not identical to any known sequence. The new organism represented by this sequence was designated strain BA-TF. A new primer was designed, p93E, that corresponds to a highly conserved 16S rRNA sequence at an upstream site. With the use of this primer and p13B, a 480-bp DNA product was amplified from the splenic extract from Patient 1, but not from that from the patient with idiopathic thrombocytopenic purpura or from other nondiseased splenic DNA extracts (data not shown). On the basis of the sequence of this 480-bp fragment, two BA-TF—specific primers — p24E and p12B — were designed (Table 1). These two primer sites are separated by 241 bp and are maximally divergent from known 16S rRNA sequences of eubacteria in those regions.
The two specific primers reproducibly amplified a DNA fragment of the expected size from a spleen sample (Fig. 2, lane 9) and a sample of splenic hilar lymph node from Patient 1 after 35 cycles of PCR. Reaction mixtures without the DNA template, as well as with DNA from tonsillar tissues from two patients and splenic tissue from patients without bacillary angiomatosis, were consistently negative. The absence of detectable product with bacterially contaminated tonsillar tissue demonstrated the specificity of these primers (Fig. 2, lane 8).
Analysis of a Novel 16S rRNA Sequence Found in Unrelated Patients with Bacillary Angiomatosis
To determine whether strain BA-TF was associated with other cases of bacillary angiomatosis, we obtained diseased tissue from three other patients, each seen at other institutions — frozen bone marrow from Patient 2, paraffin-embedded, formalin-fixed skin tissue from Patient 3, and paraffin-embedded, formalin-fixed lymph-node tissue from Patient 4. All three samples yielded a PCR product of the same expected size when the specific primers were used (Fig. 2, lanes 10 through 12). Forty cycles of amplification were performed with DNA extracted from formalin-fixed, paraffin-embedded tissues. These DNA products were cloned and sequenced. To minimize any chance of carryover contamination from our laboratory, tissue from Patients 3 and 4 was studied at a site distant from the Stanford campus.
The DNA sequence determined from the frozen tissue from Patient 2 was identical to that of BA-TF throughout the 241 base positions in the amplified fragment. One of two recombinant clones from the formalin-fixed tissue from Patient 4 had the same sequence as BA-TF; the other clone had a sequence that differed from BA-TF at 2 of 241 positions. Two recombinant clones from Patient 3 were sequenced; these sequences were found to be identical and differed from the BA-TF sequence at only 4 positions. To determine whether this sequence heterogeneity might be found with frozen tissue samples as well, the product amplified from the frozen splenic hilar lymph-node tissue from Patient 1 with the specific primers was cloned. In comparison with the original splenic BA-TF sequence, there was 1 nucleotide substitution of a total of 1350 positions from eight clones. This result is consistent with previously published error frequencies for thermostable Taq polymerase during amplification of undamaged human genomic DNA.22
Optimized sequence alignments were prepared with use of the 480-bp 16S rRNA sequence of BA-TF (excluding the primer sequences) and those of other organisms. These alignments were used to construct a phylogenetic tree according to standard techniques.36 , 37 As shown in Figure 3Figure 3
Phylogenetic Trees., strain BA-TF falls within the α subdivision of purple eubacteria and specifically within the R. quintana—Agrobacterium tumefaciens complex. This tree is consistent with the evolutionary relation of the purple eubacteria and the tribe Rickettsieae, on the basis of comparisons of full-length 16S rRNA gene sequences.38 Table 2Table 2
16S rRNA Sequence Similarities between the New Organism, BA-TF, and Selected Rickettsia and Other Eubacteria. shows the percent sequence similarities between BA-TF and other eubacteria. Even though the data in the table are based on selected 16S rRNA sequence positions, calculations of sequence similarities using the entire available BA-TF sequence gave equivalent results (data not shown). In a similar fashion we analyzed the sequence from Patient 3 and the deviant sequence from Patient 4. The results for each showed no significant difference from the analysis for BA-TF: the same relations to other organisms were confirmed. The sequence from Patient 3 was even more closely related to R. quintana; this limited portion of the 16S rRNA sequence was identical to the corresponding region of the R. quintana 16S rRNA sequence. Phylogenetic trees, constructed from each of these two deviant sequences, were nearly identical to the original (data not shown). The 480-bp 16S rRNA sequence from BA-TF has been deposited in the GenBank/European Molecular Biology Laboratory data libraries.Using the broad-range primers p93E and p13B, no irradiation of reagents, and 40 cycles of PCR, we occasionally obtained a visible DNA product when no DNA template or extract was added to the reaction mixture. The DNA product from two such reactions was cloned and sequenced. In these cases the sequences were identical to each other and were most closely related to Pseudomonas cepacia, a β purple eubacterium commonly found in aquatic environments (data not shown). These findings strengthen the specificity of the association between the BA-TF sequence and bacillary angiomatosis.
Many of the human pathogens closely related to strain BA-TF are in the tribe Rickettsieae, although this tribe is phylogenetically dispersed throughout the purple eubacterial phylum.38 Brucella abortus is the second most closely related organism to BA-TF among those whose 16S rRNA sequences have been characterized. According to our analysis, BA-TF is a unique rickettsia-like organism that is most closely related to R. quintana, the causative agent of trench fever. A. tumefaciens and other bacteria in this complex are plant pathogens and soil organisms, suggesting that BA-TF, as well as some other rickettsia, may have arisen as a plant-associated organism.39
Discussion
Our understanding of microbial pathogens and the diseases they cause is limited by our ability to cultivate these organisms. A number of human diseases are linked to microbes that can be consistently visualized but not grown. Their identity has been a mystery. We have applied a technique that circumvents the absolute need to isolate or grow a disease-associated organism but that nonetheless may reveal its phylogenetic relation. Such relations may predict important and useful features of an organism, since evolutionarily related organisms are expected to share some characteristics.
Bacillary angiomatosis is a well-defined, increasingly common infection of the skin and visceral organs, most often seen in immunocompromised hosts, especially patients with HIV infection.8 , 40 It is potentially fatal if not treated. The numerous bacilli found in the lesions of this disease have been compared to those seen in lesions from cat scratch disease, although the vascular proliferative response in bacillary angiomatosis is not a common feature of cat scratch disease. The bacilli in each disease are pleomorphic, measure 0.2 to 0.5 μm by 1 to 3 μm, grow in clumps, and have trilaminar walls.4 These bacilli have resisted identification. We have used eubacterial broad-range primers to amplify a novel 16S rDNA sequence from diseased tissue from four unrelated patients with bacillary angiomatosis. The sequence obtained from three of these patients was identical; we designated it the reference sequence, BA-TF. The sequences found in the third patient and in one clone from the fourth differed from BA-TF only minimally. None of these sequences were detected in tissues from patients without bacillary angiomatosis. On the basis of our phylogenetic analysis of these sequences, we conclude that bacillary angiomatosis is caused by a rickettsia-like organism, most closely related to R. quintana. Even though the sequence in the third patient was identical to the corresponding region of the R. quintana 16S rRNA gene, the limited amount of available sequences from this patient and the predominance of the BA-TF sequence in the other patients with bacillary angiomatosis suggest that BA-TF more accurately reflects the true 16S rRNA sequence of the pathogen. Given the paucity of a purple bacterial 16S rRNA sequences, it is not yet possible to assign BA-TF to a genus or species; however, the sequence similarity between BA-TF and R. quintana is the same as that between Rickettsia typhi and Rickettsia rickettsii (98.3 percent).
PCR is an extremely sensitive method of detecting target DNA sequences. Sequences of 16S rRNA can be amplified and compared with a reference-sequence data base in order to infer phylogenetic relations.24 , 35 The use of broad-range or "universal" 16S rRNA primers,23 however, presents special problems. Contamination of PCR reagents and target with a few bacteria, bacterial genomes, or very small amounts of eukaryotic DNA is virtually impossible to prevent and can lead to false positive results. Exquisite care must be taken to keep contamination to a minimum.41 , 42 We found that the use of no more than 25 PCR cycles with broad-range primers prevented the detection of product with uninfected tissues (unpublished data). Ultraviolet irradiation has been shown to reduce carryover contamination of PCR reagents and was useful in our 40-cycle amplifications.43 , 44 The use of specific primers reduces the need for such stringency. Our association of the BA-TF sequence with tissue from patients with bacillary angiomatosis was strengthened by the independent processing and amplification of the various samples in different laboratories. In addition, samples of internal tissue from patients without bacillary angiomatosis never produced a visible amplification product.
Despite the small number of nucleotide differences between BA-TF and the 16S rRNA sequence of Patient 3 and of a single clone from Patient 4, these sequences are all related to 16S rRNA sequences of the same organisms. On the basis of the 16S rRNA nucleotide positions included in our phylogenetic analysis, the sequences from these two patients differed by only 0.7 percent from the BA-TF sequence. However, these differences do raise some important issues. Could sequence heterogeneity indicate the presence of multiple but related strains within the diseased tissue — i.e., a mixed infection? This is unlikely for two reasons. First, at rRNA positions known to participate in the formation of base pairs in secondary structures, we have seen nucleotide substitutions without compensatory substitutions at the corresponding paired position; such changes would be disruptive to the rRNA secondary structure. Second, sequence heterogeneity was apparent only in Patients 3 and 4, for whom formalin-fixed tissue was studied. Another possibility is that the heterogeneity is due in part to the amplification of different copies of the 16S rRNA gene from the same organism. A small number of nucleotide differences are known to exist within the seven copies of the E. coli rRNA genes.45 , 46 This possibility cannot be ruled out for BA-TF; however, the explanation we most favor for the observed sequence differences is Taq polymerase error. Taq polymerase can mistakenly incorporate nucleotides, particularly during the amplification of damaged DNA.47 , 48 Formalin fixation can damage nucleic acids at particular positions and therefore contributes to higher polymerase-error rates. Under these conditions, when there are few original templates in a tissue sample, it is imperative to sequence multiple clones of the amplified product.
Complete 16S rRNA sequences are not necessary for the construction of meaningful phylogenetic trees23; however, the amount of partial sequence available and the composition of the reference 16S rRNA sequence collection are important variables. Our evolutionary-distance tree duplicated the relations among the Rickettsieae and other purple bacteria established by Weisburg et al. using full 16S rRNA sequences.38 Thus, we are confident about our phylogenetic analysis of strain BA-TF. In addition, a rickettsial origin is consistent with previous morphologic descriptions of the bacillus causing bacillary angiomatosis.
What are the implications of the relation between BA-TF, R. quintana, and other α purple bacteria? R. quintana is transmitted by the body louse and is the cause of trench fever, a systemic illness characterized by persistent or recurrent fever, bone and muscle pain, rash, and splenomegaly.49 R. quintana is sensitive in vitro to erythromycin and the tetracyclines,50 agents that have been used successfully to treat bacillary angiomatosis.40 Although trench fever and disseminated bacillary angiomatosis share some clinical features, the vascular lesions of bacillary angiomatosis distinguish it from trench fever. A separate member of the order Rickettsiales, Bartonella bacilliformis, can produce lesions (verruga peruana) that are indistinguishable from those caused by bacillary angiomatosis, and this has led to suggestions that it might be the cause of this disease.4 , 51 There are no 16S rRNA sequence data available for Bart. bacilliformis; therefore, its relation to BA-TF remains unclear. B. abortus has features in common with the agent of bacillary angiomatosis: both are transmitted to humans from domestic animals by percutaneous inoculation, frequently involve the reticuloendothelial system, and can cause chronic febrile illnesses. On the other hand, infrequent skin involvement, a granulomatous rather than a vascular proliferative host-tissue response, a gram-negative staining pattern, and 16S rRNA sequence distinguish brucellosis from bacillary angiomatosis.52
The grouping of R. quintana and BA-TF with the agrobacteria and rhizobacteria suggests a plant or soil origin.39 Humans are the only known reservoir for R. quintana, but the other characterized member of this genus, R. vinsonii, is carried by voles.53 The grouping of BA-TF with these organisms would be consistent with its transmission from the environment to humans by means of a break in the skin. What role, if any, cats have, and the exact relation of BA-TF to the bacillus of cat scratch disease must await further analysis of the latter organism. We are currently using the techniques described in this report to identify the cat-scratch-disease bacillus.
R. quintana is the only pathogenic rickettsia to grow on cell-free medium.54 The relation of BA-TF to this organism may help us develop appropriate culture conditions for the growth of this new pathogen. Growth of BA-TF would facilitate the investigation of the angioproliferative response it elicits in the host.40 Our results also have implications for the diagnosis of bacillary angiomatosis: divergent portions of the BA-TF 16S rRNA gene or adjacent regions of the genome may serve as probes for in situ hybridization. If such probes were labeled with fluorescent dyes, hybridization to the agent of bacillary angiomatosis could be visualized with epifluorescence.55 Alternatively, an in situ PCR-based technique might be feasible.
The discovery of this novel rickettsia-like organism in patients with bacillary angiomatosis is one example of the application of a potentially powerful technique. We expect that this approach will be applicable to other infectious diseases with unclear causes and will expand our understanding of interactions between humans and microbes.
Supported by Public Health Service grants (AI 26195 [Dr. Falkow] and AI 23796 [Dr. Tompkins]) from the National Institutes of Health, a contract (N14–87-K-0813 [Dr. Schmidt]) with the Office of Naval Research, and an unrestricted gift from Praxis Biologics, Rochester, N. Y. Dr. Relman is a recipient of a Lucille P. Markey Scholar Award in Biomedical Science.
We are indebted to Drs. Carol Kemper and Stanley Deresinski and our other clinical colleagues for their support and enthusiasm; to Dr. Norman Pace, Indiana University, for advice, constructive suggestions, and access to data bases; to Dr. Donald Regula, Department of Pathology, Stanford University, for providing invaluable assistance with tissue samples from Patient 1 and photographs; to Dr. Kemper, Santa Clara Valley Medical Center, San Jose, for providing tissue from Patient 2; to Dr. Philip LeBoit, Department of Pathology, University of California, San Francisco, for providing tissue from Patient 3; to Dr. Ronald F. Dorfman, Department of Pathology, Stanford University, and Dr. Klaus J. Lewin, Department of Pathology, University of California, Los Angeles, for providing tissue from Patient 4; and to Dr. Michele Manos and Ms. Catherine Greer, Cetus Corporation, Emeryville, California, for giving us valuable advice about and assistance with the extraction of DNA from formalin-fixed, paraffin-embedded tissue.
Source Information
From the Department of Microbiology and Immunology (D.A.R., S.F., L.S.T.) and the Division of Infectious Diseases, Department of Medicine (D.A.R., J.S.L., S.F., L.S.T.), Stanford University, Stanford, Calif., and the Department of Biology, Indiana University, Bloomington (T.M.S.). Address reprint requests to Dr. Relman at the Department of Microbiology and Immunology, Fairchild Building D309, Stanford University, Stanford, CA 94305–5402.
- References
References
1
Stoler
Web of Science | Medline2
Cockerell
CrossRef | Web of Science | Medline3
Angritt
CrossRef | Web of Science | Medline4
LeBoit
CrossRef | Web of Science | Medline5
LeBoit
CrossRef | Web of Science | Medline6
Koehler
Web of Science | Medline7
Milam
CrossRef | Web of Science | Medline8
Kemper
CrossRef | Web of Science | Medline9
Cockerell
CrossRef | Web of Science | Medline10
Carithers
CrossRef | Web of Science | Medline11
Carithers
Web of Science | Medline12
Margileth
CrossRef | Web of Science | Medline13
Lenoir
CrossRef | Web of Science | Medline14
Delahoussaye
CrossRef | Web of Science | Medline15
Wear
CrossRef | Web of Science | Medline16
English
CrossRef | Web of Science | Medline17
Schlossberg
CrossRef | Web of Science | Medline18
Fox
CrossRef | Web of Science | Medline19
Woese
Medline20
Saiki
CrossRef | Web of Science | Medline21
Mullis KB, Faloona FA. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. In: Methods in enzymology. Vol. 155. Wu R, ed., Recombinant DNA, Part F. San Diego: Academic Press, 1987:335–50.
22
Saiki
CrossRef | Web of Science | Medline23
Lane
CrossRef | Web of Science | Medline24
Medlin
CrossRef | Web of Science | Medline25
Eisenstein
Full Text | Web of Science | Medline26
Chen
CrossRef | Web of Science | Medline27
Goelz
CrossRef | Web of Science | Medline28
Dubeau
Web of Science | Medline29
Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. 2nd ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory, 1989.
30
Shibata
CrossRef | Web of Science | Medline31
Wright DK, Manos MM. Sample preparation from paraffin-embedded tissues. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ, eds. PCR protocols: a guide to methods and applications. San Diego, Calif.: Academic Press, 1990:153–8.
32
Dower
CrossRef | Web of Science | Medline33
Sanger
CrossRef | Web of Science | Medline34
Jukes TH, Cantor CR. Evolution of protein molecules. In: Munro HN, ed. Mammalian protein metabolism. Vol. 3. New York: Academic Press, 1969:21–132.
35
Olsen
Web of Science | Medline36
Fitch
CrossRef | Web of Science | Medline37
Turner
CrossRef | Web of Science | Medline38
Weisburg
Web of Science | Medline39
Weisburg
CrossRef | Web of Science | Medline40
Cockerell
CrossRef | Web of Science | Medline41
Kwok
CrossRef | Web of Science | MedlineErratum , Nature 1989; 339:490.
Web of Science42
Kitchin
CrossRef | Web of Science | Medline43
Sarkar
CrossRef | Web of Science | Medline44
Cimino
CrossRef | Web of Science | Medline45
Brownlee
CrossRef | Web of Science | Medline46
Jinks-Robertson S, Nomura M. Ribosomes and tRNA. In: Neidhardt FC, ed. Escherichia coli and Salmonella typhimurium: cellular and molecular biology. 2. Washington, D.C.: American Society for Microbiology, 1987:1358–85.
47
Pääbo
Web of Science | Medline48
Ennis
CrossRef | Web of Science | Medline49
Vinson
Web of Science | Medline50
Myers
Web of Science | Medline51
Kreier
CrossRef | Web of Science | Medline52
Spink WW. The nature of brucellosis. Minneapolis: University of Minnesota Press, 1956.
53
Weiss
CrossRef54
Varela
Web of Science | Medline55
DeLong
CrossRef | Web of Science | MedlineErratum , Science 1989; 245:1312.
- Citing Articles (204)
Citing Articles
1
R. Schalberg, . (2012) A Systematic Approach for Discovering Novel, Clinically Relevant Bacteria. Emerging Infectious Diseases 18:3,
CrossRef2
Ju-Hsin Chia, Tsu-Lan Wu, Lin-Hui Su, An-Jing Kuo, Hsin-Chih Lai. (2012) Direct identification of mycobacteria from smear-positive sputum samples using an improved multiplex polymerase chain reaction assay. Diagnostic Microbiology and Infectious Disease
CrossRef3
Patrick O. Kaiser, Dirk Linke, Heinz Schwarz, Jack C. Leo, Volkhard A. J. Kempf. (2011) Analysis of the BadA stalk from Bartonella henselae reveals domain-specific and domain-overlapping functions in the host cell infection process. Cellular Microbiologyno-no
CrossRef4
Pierre-Edouard Fournier, Didier Raoult. (2011) Prospects for the Future Using Genomics and Proteomics in Clinical Microbiology. Annual Review of Microbiology 65:1, 169-188
CrossRef5
Hiroshi Miura, Masaki Ogawa, Hideto Hirano, Hiroyuki Sanada, Akira Sato, Mikitaka Obara, Yukihiro Terada. (2011) Neutrophil elastase and interleukin-6 in amniotic fluid as indicators of chorioamnionitis and funisitis. European Journal of Obstetrics & Gynecology and Reproductive Biology 158:2, 209-213
CrossRef6
Jean Stiles. (2011) Bartonellosis in cats: a role in uveitis?. Veterinary Ophthalmology 14, 9-14
CrossRef7
Valentina V. Ebani, Fabrizio Bertelloni, Filippo Fratini. (2011) Occurrence of Bartonella henselae types I and II in Central Italian domestic cats. Research in Veterinary Science
CrossRef8
Feero, W. Gregory, Guttmacher, Alan E., , Relman, David A., . (2011) Microbial Genomics and Infectious Diseases. New England Journal of Medicine 365:4, 347-357
Full Text9
Bradley M Mitchell, Ramon L Font. (2011) Molecular Detection of Bartonella henselae for the Diagnosis of Cat Scratch Disease and Bacillary Angiomatosis of the Conjunctiva. Cornea 30:7, 807-814
CrossRef10
DANNY MORICK, BORIS R. KRASNOV, IRINA S. KHOKHLOVA, YUVAL GOTTLIEB, SHIMON HARRUS. (2011) Investigation of Bartonella acquisition and transmission in Xenopsylla ramesis fleas (Siphonaptera: Pulicidae). Molecular Ecology 20:13, 2864-2870
CrossRef11
Diana B. McShane, Heidi H. Kong, Sarah A. Myers. 2011. Bartonella Infections: Bacillary Angiomatosis, Cat Scratch Disease and Bartonellosis. , 58.1-58.10.
CrossRef12
Muhammad Nawaz, Juan Wang, Aiping Zhou, Chaofeng Ma, Xiaokang Wu, John E. Moore, B. Cherie Millar, Jiru Xu. (2011) Characterization and Transfer of Antibiotic Resistance in Lactic Acid Bacteria from Fermented Food Products. Current Microbiology 62:3, 1081-1089
CrossRef13
A.-L. Roux, V. Sivadon-Tardy, T. Bauer, A. Lortat-Jacob, J.-L. Herrmann, J.-L. Gaillard, M. Rottman. (2011) Diagnosis of prosthetic joint infection by beadmill processing of a periprosthetic specimen. Clinical Microbiology and Infection 17:3, 447-450
CrossRef14
Chien-Hong Chou, Hsin-Yi Chen, Chung-Yu Chen, Chun-Ta Huang, Chih-Cheng Lai, Po-Ren Hsueh. (2011) Clinical features and outcomes of disseminated infections caused by non-tuberculous mycobacteria in a university hospital in Taiwan, 2004–2008. Scandinavian Journal of Infectious Diseases 43:1, 8-14
CrossRef15
Bettina Franz, Volkhard AJ Kempf. (2011) Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae. Parasites & Vectors 4:1, 54
CrossRef16
Fred C. Tenover. (2010) Potential impact of rapid diagnostic tests on improving antimicrobial use. Annals of the New York Academy of Sciences 1213:1, 70-80
CrossRef17
J.R. Barreiro, C.R. Ferreira, G.B. Sanvido, M. Kostrzewa, T. Maier, B. Wegemann, V. Böttcher, M.N. Eberlin, M.V. dos Santos. (2010) Short communication: Identification of subclinical cow mastitis pathogens in milk by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Journal of Dairy Science 93:12, 5661-5667
CrossRef18
Daniel B. DiGiulio, MariaTeresa Gervasi, Roberto Romero, Shali Mazaki-Tovi, Edi Vaisbuch, Juan Pedro Kusanovic, Kimberley S. Seok, Ricardo Gómez, Pooja Mittal, Francesca Gotsch, Tinnakorn Chaiworapongsa, Enrique Oyarzún, Chong Jai Kim, David A. Relman. (2010) Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. Journal of Perinatal Medicine 38:5, 503-513
CrossRef19
Daniel B. DiGiulio, Maria Teresa Gervasi, Roberto Romero, Edi Vaisbuch, Shali Mazaki-Tovi, Juan Pedro Kusanovic, Kimberley S. Seok, Ricardo Gómez, Pooja Mittal, Francesca Gotsch, Tinnakorn Chaiworapongsa, Enrique Oyarzún, Chong Jai Kim, David A. Relman. (2010) Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses. Journal of Perinatal Medicine 38:5, 495-502
CrossRef20
Anna Sander. 2010. Bartonella and Afipia. .
CrossRef21
(2010) Update on Emerging Infections: News From the Centers for Disease Control and Prevention. Annals of Emergency Medicine 55:3, 280-282
CrossRef22
Daniel B. DiGiulio, Roberto Romero, Juan Pedro Kusanovic, Ricardo Gómez, Chong Jai Kim, Kimberley S. Seok, Francesca Gotsch, Shali Mazaki-Tovi, Edi Vaisbuch, Katherine Sanders, Elisabeth M. Bik, Tinnakorn Chaiworapongsa, Enrique Oyarzún, David A. Relman. (2010) Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre-Labor Rupture of Membranes. American Journal of Reproductive Immunology
CrossRef23
Dan G. Ohad, Danny Morick, Boaz Avidor, Shimon Harrus. (2010) Molecular detection of Bartonella henselae and Bartonella koehlerae from aortic valves of Boxer dogs with infective endocarditis. Veterinary Microbiology 141:1-2, 182-185
CrossRef24
Emmanuel Lemichez, Marc Lecuit, Xavier Nassif, Sandrine Bourdoulous. (2010) Breaking the wall: targeting of the endothelium by pathogenic bacteria. Nature Reviews Microbiology
CrossRef25
Sunlian Feng, Rickie W. Kasten, Jonathan A. Werner, Emir Hodzic, Stephen W. Barthold, Bruno B. Chomel. (2009) Immunogenicity of Bartonella henselae P26 in cats. Veterinary Immunology and Immunopathology 132:2-4, 251-256
CrossRef26
R. Zobba, G. Chessa, S. Mastrandrea, M. L. Pinna Parpaglia, C. Patta, G. Masala. (2009) Serological and molecular detection of Bartonella spp. in humans, cats and dogs from northern Sardinia, Italy. Clinical Microbiology and Infection 15, 134-135
CrossRef27
Megan C. Morgan, Marilyn Boyette, Chris Goforth, Katharine Volpe Sperry, Shermalyn R. Greene. (2009) Comparison of the Biolog OmniLog Identification System and 16S ribosomal RNA gene sequencing for accuracy in identification of atypical bacteria of clinical origin. Journal of Microbiological Methods 79:3, 336-343
CrossRef28
Elisabeth M Bik. (2009) Composition and function of the human-associated microbiota. Nutrition Reviews 67, S164-S171
CrossRef29
Koenraad J. Mortelé, Hope E. Peters. (2009) Multimodality Imaging of Common and Uncommon Cystic Focal Liver Lesions. Seminars in Ultrasound, CT, and MRI 30:5, 368-386
CrossRef30
W. Ian Lipkin, Gustavo Palacios, Thomas Briese. (2009) Diagnostics and Discovery in Viral Hemorrhagic Fevers. Annals of the New York Academy of Sciences 1171, E6-E11
CrossRef31
Michael F Minnick, James M Battisti. (2009) Pestilence, persistence and pathogenicity: infection strategies of Bartonella. Future Microbiology 4:6, 743-758
CrossRef32
Ciro Maguiña, Humberto Guerra, Palmira Ventosilla. (2009) Bartonellosis. Clinics in Dermatology 27:3, 271-280
CrossRef33
Nikolaos P. Polyzos, Ilias P. Polyzos, Davide Mauri, Spyridon Tzioras, Maria Tsappi, Ivan Cortinovis, Giovanni Casazza. (2009) Effect of periodontal disease treatment during pregnancy on preterm birth incidence: a metaanalysis of randomized trials. American Journal of Obstetrics and Gynecology 200:3, 225-232
CrossRef34
Sushama Sontakke, Maria B. Cadenas, Ricardo G. Maggi, Pedro Paulo V.P. Diniz, Edward B. Breitschwerdt. (2009) Use of broad range16S rDNA PCR in clinical microbiology. Journal of Microbiological Methods 76:3, 217-225
CrossRef35
Jaana Renko, Paul W. Lepp, Niku Oksala, Simo Nikkari, Seppo T. Nikkari. (2008) Bacterial signatures in atherosclerotic lesions represent human commensals and pathogens. Atherosclerosis 201:1, 192-197
CrossRef36
Gerd Döring, Klaus Unertl, Alexandra Heininger. (2008) Validation criteria for nucleic acid amplification techniques for bacterial infections. Clinical Chemistry and Laboratory Medicine 46:7, 909-918
CrossRef37
Stefanie Kunz, Karin Oberle, Anna Sander, Christian Bogdan, Ulrike Schleicher. (2008) Lymphadenopathy in a Novel Mouse Model of Bartonella-Induced Cat Scratch Disease Results from Lymphocyte Immigration and Proliferation and Is Regulated by Interferon-α/β. The American Journal of Pathology 172:4, 1005-1018
CrossRef38
Laura MacConaill, Matthew Meyerson. (2008) Adding pathogens by genomic subtraction. Nature Genetics 40:4, 380-382
CrossRef39
Chen-Hsiang Lee, Wei-Che Lin, Ju-Hsin Chia, Lin-Hui Su, Chun-Chih Chien, Ai-Hsiu Mao, Jien-Wei Liu. (2008) Community-acquired osteomyelitis caused by Chryseobacterium meningosepticum: case report and literature review. Diagnostic Microbiology and Infectious Disease 60:1, 89-93
CrossRef40
Jane E. Koehler. 2008. Bartonella Infections in HIV-infected Individuals. , 425-436.
CrossRef41
Robert L Goldenberg, Jennifer F Culhane, Jay D Iams, Roberto Romero. (2008) Epidemiology and causes of preterm birth. The Lancet 371:9606, 75-84
CrossRef42
D. Raoult. (2007) From Cat Scratch Disease to Bartonella henselae Infection. Clinical Infectious Diseases 45:12, 1541-1542
CrossRef43
Pierre-Edouard Fournier, Michel Drancourt, Didier Raoult. (2007) Bacterial genome sequencing and its use in infectious diseases. The Lancet Infectious Diseases 7:11, 711-723
CrossRef44
Luiz Vicente F. da Silva Filho, Adriana F. Tateno, Kátia M. Martins, Ana Carolina Azzuz Chernishev, Doroti de Oliveira Garcia, Maria Haug, Christoph Meisner, Joaquim C. Rodrigues, Gerd Döring. (2007) The combination of PCR and serology increases the diagnosis ofPseudomonas aeruginosa colonization/infection in cystic fibrosis. Pediatric Pulmonology 42:10, 938-944
CrossRef45
B. M. W. Diederen, M. J. Vermeulen, H. Verbakel, A. Zee, A. Bergmans, M. F. Peeters. (2007) Evaluation of an internally controlled real-time polymerase chain reaction assay targeting the groEL gene for the detection of Bartonella spp. DNA in patients with suspected cat-scratch disease. European Journal of Clinical Microbiology & Infectious Diseases 26:9, 629-633
CrossRef46
Eremeeva, Marina E., Gerns, Helen L., Lydy, Shari L., Goo, Jeanna S., Ryan, Edward T., Mathew, Smitha S., Ferraro, Mary Jane, Holden, Judith M., Nicholson, William L., Dasch, Gregory A., Koehler, Jane E., . (2007) Bacteremia, Fever, and Splenomegaly Caused by a Newly Recognized Bartonella Species. New England Journal of Medicine 356:23, 2381-2387
Full Text47
Howard L. Lipton, Zhiguo Liang, Shannon Hertzler, Kyung-No Son. (2007) A specific viral cause of multiple sclerosis: One virus, one disease. Annals of Neurology 61:6, 514-523
CrossRef48
Nawale Hajjaji, Laurent Hocqueloux, Rémy Kerdraon, Laurent Bret. (2007) Bone infection in cat-scratch disease: A review of the literature. Journal of Infection 54:5, 417-421
CrossRef49
L. B. Reller, M. P. Weinstein, C. A. Petti. (2007) Detection and Identification of Microorganisms by Gene Amplification and Sequencing. Clinical Infectious Diseases 44:8, 1108-1114
CrossRef50
M. Yu. Kirillov, A. P. Markov, I. V. Lopyrev, V. N. Pankratova, S. A. Levitskii, V. N. Bashkirov, G. B. Smirnov, A. N. Kruglov, V. A. Osadchaya, G. P. Frolova, G. V. Barmina, O. A. Morozova, M. Y. Kosoy. (2007) Molecular genetic techniques for typing of Bartonella isolates. Molecular Genetics, Microbiology and Virology 22:1, 7-15
CrossRef51
Risa M. Hoffman, Jamil AboulHosn, John S. Child, David A. Pegues. (2007) Bartonella Endocarditis in Complex Congenital Heart Disease. Congenital Heart Disease 2:1, 79-84
CrossRef52
R Romero, J Espinoza, JP Kusanovic, F Gotsch, S Hassan, O Erez, T Chaiworapongsa, M Mazor. (2006) The preterm parturition syndrome. BJOG: An International Journal of Obstetrics & Gynaecology 113, 17-42
CrossRef53
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Rosenberg, Eric S., Cort, Alice M., Ebeling, Sally H.Peters, Christine C., Pelton, Stephen I., Kim, John Y., Kradin, Richard L., . (2006) Case 27-2006. New England Journal of Medicine 355:9, 941-948
Full Text54
C.Y. Hsieh, M.C. Tung, C. Tu, C.D. Chang, S.S. Tsai. (2006) Enzootics of visceral granulomas associated with Francisella-like organism infection in tilapia (Oreochromis spp.). Aquaculture 254:1-4, 129-138
CrossRef55
Mardjan Arvand, Hannah Schubert, Juliane Viezens. (2006) Emergence of distinct genetic variants in the population of primary Bartonella henselae isolates. Microbes and Infection 8:5, 1315-1320
CrossRef56
Sean Amsbaugh, Erin Huiras, Nadia S Wang, Aaron Wever, Simon Warren. (2006) Bacillary Angiomatosis Associated With Pseudoepitheliomatous Hyperplasia. The American Journal of Dermatopathology 28:1, 32-35
CrossRef57
2005. Hypertension (High Blood Pressure). .
CrossRef58
2005. Arteries and Veins (Vascular System). .
CrossRef59
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Ebeling, Sally H.Ellender, Stacey M.Peters, Christine C., Koehler, Jane E., Duncan, Lyn M., . (2005) Case 30-2005. New England Journal of Medicine 353:13, 1387-1394
Full Text60
A McOrist, G Veuilett, M Vuaran, A Bird, M Noakes, D Topping. (2005) Population and virulence factor dynamics in fecal Escherichia coli from healthy adults consuming weight control diets. Canadian Journal of Microbiology 51:6, 467-475
CrossRef61
O. Yildiz, E. Alp, B. Tokgoz, B. Tucer, B. Aygen, B. Sumerkan, A. Couble, P. Boiron, M. Doganay. (2005) Nocardiosis in a teaching hospital in the Central Anatolia region of Turkey: treatment and outcome. Clinical Microbiology and Infection 11:6, 495-499
CrossRef62
Evelio J. Perea. (2005) La microbiología oral en la era de la genómica y la proteómica. Enfermedades Infecciosas y Microbiología Clínica 23:3, 113-115
CrossRef63
J. Lehtiniemi, P. J. Karhunen, S. Goebeler, S. Nikkari, S. T. Nikkari. (2005) Identification of different bacterial DNAs in human coronary arteries. European Journal of Clinical Investigation 35:1, 13-16
CrossRef64
FLORENCE FENOLLAR, DIDIER RAOULT. (2004) Molecular genetic methods for the diagnosis of fastidious microorganisms. APMIS 112:11-12, 785-807
CrossRef65
Christoph Dehio. (2004) MOLECULAR AND CELLULAR BASIS OF BARTONELLA PATHOGENESIS. Annual Review of Microbiology 58:1, 365-390
CrossRef66
Susanna K.P Lau, Patrick C.Y Woo, Gibson K.S Woo, Ami M.Y Fung, Michelle K.M Wong, King-man Chan, Dorothy M.W Tam, Kwok-yung Yuen. (2004) Eggerthella hongkongensis sp. nov. and eggerthella sinensis sp. nov., two novel Eggerthella species, account for half of the cases of Eggerthella bacteremia. Diagnostic Microbiology and Infectious Disease 49:4, 255-263
CrossRef67
Potharaju Anuradha, Roya Rozati, K. Thangraj, G. Khatri, P. Hanumantharao. (2004) Molecular screening of unculturable bacteria present in men with reproductive failure. Reproductive Medicine and Biology 3:2, 77-84
CrossRef68
Luiz V.F. da Silva Filho, Adriana F. Tateno, Luciana de F. Velloso, Jos
E. Levi, Silvana Fernandes, Christina N.O. Bento, Joaquim C. Rodrigues, Sonia R.T.S. Ramos. (2004) Identification ofPseudomonas aeruginosa,Burkholderia cepacia complex, andStenotrophomonas maltophilia in respiratory samples from cystic fibrosis patients using multiplex PCR. Pediatric Pulmonology 37:6, 537-547
CrossRef69
Patel, Uptal D., Hollander, Harry, Saint, Sanjay, . (2004) Index of Suspicion. New England Journal of Medicine 350:19, 1990-1995
Full Text70
A. Heininger, M. Binder, A. Ellinger, J. Pfisterer, K. Botzenhart, K. Unertl, G. Doering. (2004) Effect of comprehensive validation of the template isolation procedure on the reliability of bacteraemia detection by a 16S rRNA gene PCR. Clinical Microbiology and Infection 10:5, 452-458
CrossRef71
(2004) Immunoproliferative Small Intestinal Disease Associated with Campylobacter jejuni. New England Journal of Medicine 350:16, 1685-1686
Full Text72
A. Escarmelle, N. Delbrassine, P. De Potter. (2004) Maladie des griffes du chat et syndrome oculo-glandulaire de Parinaud. Journal Français d'Ophtalmologie 27:2, 179-183
CrossRef73
Lecuit, Marc, Abachin, Eric, Martin, Antoine, Poyart, Claire, Pochart, Philippe, Suarez, Felipe, Bengoufa, Djaouida, Feuillard, Jean, Lavergne, Anne, Gordon, Jeffrey I., Berche, Patrick, Guillevin, Loïc, Lortholary, Olivier, . (2004) Immunoproliferative Small Intestinal Disease Associated with Campylobacter jejuni. New England Journal of Medicine 350:3, 239-248
Full Text74
J. E. Koehler, M. A. Sanchez, S. Tye, C. S. Garrido-Rowland, F. M. Chen, T. Maurer, J. L. Cooper, J. G. Olson, A. L. Reingold, W. K. Hadley, R. R. Regnery, J. W. Tappero. (2003) Prevalence of Bartonella Infection among Human Immunodeficiency Virus--Infected Patients with Fever. Clinical Infectious Diseases 37:4, 559-566
CrossRef75
J. Renko, A. Kalela, P. J. Karhunen, H. Helin, P. Sillanaukee, S. Nikkari, S. T. Nikkari. (2003) Do temporal arteritis lesions contain bacterial DNA?. European Journal of Clinical Investigation 33:8, 657-661
CrossRef76
Yaohui Xu, Nicole Stange-Thomann, Griffin Weber, Ronghai Bo, Sheila Dodge, Robert G David, Karen Foley, Javad Beheshti, Nancy L Harris, Bruce Birren, Eric S Lander, Matthew Meyerson. (2003) Pathogen discovery from human tissue by sequence-based computational subtraction. Genomics 81:3, 329-335
CrossRef77
Tao Hong, Nueda Heibler, Y.i-Wei Tang. (2003) “Bacillus hackensackii” sp. nov., a novel carbon dioxide sensitive bacterium isolated from blood culture. Diagnostic Microbiology and Infectious Disease 45:2, 143-147
CrossRef78
Hidenori KABEYA, Emiko TSUNODA, Soichi MARUYAMA, Takeshi MIKAMI. (2003) Immune Responses of Immunocompetent and Immunocompromised Mice Experimentally Infected with Bartonella henselae. Journal of Veterinary Medical Science 65:4, 479-484
CrossRef79
S. Blackwell, R. Romero, T. Chaiworapongsa, Y. M. Kim, E. Bujold, J. Espinoza, N. Camacho, S. Hassan, B. H. Yoon, J. S. Refuerzo. (2003) Maternal and fetal inflammatory responses in unexplained fetal death. Journal of Maternal-Fetal and Neonatal Medicine 14:3, 151-157
CrossRef80
Jacob Gilad, Arik Wolak, Abraham Borer, Daniel Benharroch, Boaz Avidor, Michael Giladi, Francisc Schlaeffer. (2003) Isolated Splenic Cat Scratch Disease in an Immunocompetent Adult Woman. Clinical Infectious Diseases 36:1, e10-e13
CrossRef81
M.S Jackson, A.R Bird, A.L McOrist. (2002) Comparison of two selective media for the detection and enumeration of Lactobacilli in human faeces. Journal of Microbiological Methods 51:3, 313-321
CrossRef82
Jessica L. Finkelstein, Tracy P. Brown, Kathy L. O’reilly, Jimmy Wedincamp, Lane D. Foil. (2002) Studies on the Growth of Bartonella henselae in the Cat Flea (Siphonaptera: Pulicidae). Journal of Medical Entomology 39:6, 915-919
CrossRef83
Patrick C.Y. Woo, Gibson K.S. Woo, Susanna K.P. Lau, Samson S.Y. Wong, Kwok-yung Yuen. (2002) Single gene target bacterial identification. Diagnostic Microbiology and Infectious Disease 44:2, 143-149
CrossRef84
Hidenori Kabeya, Soichi Maruyama, Mitsuhiro Irei, Rena Takahashi, Masaya Yamashita, Takeshi Mikami. (2002) Genomic variations among Bartonella henselae isolates derived from naturally infected cats. Veterinary Microbiology 89:2-3, 211-221
CrossRef85
J. Frean, S. Arndt, D. Spencer. (2002) High rate of Bartonella henselae infection in HIV-positive outpatients in Johannesburg, South Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 96:5, 549-550
CrossRef86
P Grimont. (2002) Risque bactériologique : repérage des souchesBacteriological risk: strain detection and tracing.. Comptes Rendus Biologies 325:8, 901-906
CrossRef87
Lorenzo Ciceroni, Massimo Fabbi, Simonetta Ciarrocchi, Antonella Pinto, Alessandra Ciervo, Rickie W Kasten, Bruno B Chomel. (2002) Characterization of the first Bartonella henselae strain isolated from a cat in Italy. Comparative Immunology, Microbiology and Infectious Diseases 25:4, 217-228
CrossRef88
Chao-chin Chang, Hideki Hayashidani, Nicola Pusterla, Rickie W. Kasten, John E. Madigan, Bruno B. Chomel. (2002) Investigation of Bartonella infection in ixodid ticks from California. Comparative Immunology, Microbiology and Infectious Diseases 25:4, 229-236
CrossRef89
Gwendolyn L. Gilbert. (2002) Molecular diagnostics in infectious diseases and public health microbiology: cottage industry to postgenomics. Trends in Molecular Medicine 8:6, 280-287
CrossRef90
Patrick C.Y Woo, Ami M.Y Fung, Susanna K.P Lau, Edmund Hon, Kwok-yung Yuen. (2002) Diagnosis of pelvic actinomycosis by 16S ribosomal RNA gene sequencing and its clinical significance. Diagnostic Microbiology and Infectious Disease 43:2, 113-118
CrossRef91
Volkhard A.J Kempf, Niclas Hitziger, Tanja Riess, Ingo B Autenrieth. (2002) Do plant and human pathogens have a common pathogenicity strategy?. Trends in Microbiology 10:6, 269-275
CrossRef92
Gorm Lisby, Ernö Gutschik, David T Durack. (2002) Molecular methods for diagnosis of infective endocarditis. Infectious Disease Clinics of North America 16:2, 393-412
CrossRef93
K Hercík. (2002) In situ detection of Bartonella henselae cells. Molecular and Cellular Probes 16:1, 49-56
CrossRef94
Lu
CrossRef95
A. Van Audenhove, G. Verhoef, W. E. Peetermans, M. Boogaerts, P. Vandenberghe. (2001) Autoimmune haemolytic anaemia triggered by Bartonella henselae infection: a case report. British Journal of Haematology 115:4, 924-925
CrossRef96
J TPAN. (2001) Identification of Staphylococcus aureus based on PCR amplification of species specific genomic 826 bp sequence derived from a common 44-kb Sma I restriction fragment. Molecular and Cellular Probes 15:5, 249-257
CrossRef97
Didier Raoult, Cédric Foucault, Philippe Brouqui. (2001) Infections in the homeless. The Lancet Infectious Diseases 1:2, 77-84
CrossRef98
Florence Fenollar, Didier Raoult. (2001) Molecular techniques in Whipple's disease. Expert Review of Molecular Diagnostics 1:3, 299-309
CrossRef99
Patrick C.Y. Woo, Ken T.K. Chong, Kit-wah Leung, Tak-lun Que, Kwok-yung Yuen. (2001) Identification of Arcobacter cryaerophilus isolated from a traffic accident victim with bacteremia by 16S ribosomal RNA gene sequencing. Diagnostic Microbiology and Infectious Disease 40:3, 125-127
CrossRef100
James A. Comer, Christopher D. Paddock, James E. Childs. (2001) Urban Zoonoses Caused by Bartonella , Coxiella , Ehrlichia , and Rickettsia Species. Vector-Borne and Zoonotic Diseases 1:2, 91-118
CrossRef101
A.N. Gurfield, H.-J. Boulouis, B.B. Chomel, R.W. Kasten, R. Heller, C. Bouillin, C. Gandoin, D. Thibault, C.-C. Chang, F. Barrat, Y. Piemont. (2001) Epidemiology of Bartonella infection in domestic cats in France. Veterinary Microbiology 80:2, 185-198
CrossRef102
Nathalie J. Bureau, Étienne Cardinal. (2001) Imaging of Musculoskeletal and Spinal Infections in Aids. Radiologic Clinics of North America 39:2, 343-355
CrossRef103
Patrick C.Y Woo, Elim Y.L Cheung, Kit-wah Leung, Kwok-yung Yuen. (2001) Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae species with ambiguous biochemical profile from a renal transplant recipient. Diagnostic Microbiology and Infectious Disease 39:2, 85-93
CrossRef104
Sara O. Vargas, Antonio R. Perez-Atayde, Frank González-Crussi, Harry P. Kozakewich. (2001) Giant Cell Angioblastoma. The American Journal of Surgical Pathology 25:2, 185-196
CrossRef105
L Guptill, C-C Wu, L Glickman, J Turek, L Slater, H HogenEsch. (2000) Extracellular Bartonella henselae and artifactual intraerythrocytic pseudoinclusions in experimentally infected cats. Veterinary Microbiology 76:3, 283-290
CrossRef106
Emmett T Cunningham, Jane E Koehler. (2000) Ocular bartonellosis. American Journal of Ophthalmology 130:3, 340-349
CrossRef107
Kevin L Karem, Christopher D Paddock, Russell L Regnery. (2000) Bartonella henselae, B. quintana, and B. bacilliformis: historical pathogens of emerging significance. Microbes and Infection 2:10, 1193-1205
CrossRef108
Craig Stephens. (2000) Microbiology: Intimate strangers. Current Biology 10:7, R272-R275
CrossRef109
Ely E. M. Cortes, Valeria Saraceni, Dailton Medeiros, Ida Ribeiro. (2000) Bacillary Angiomatosis and Kaposi's Sarcoma in AIDS. AIDS Patient Care and STDs 14:4, 179-182
CrossRef110
R Birtles. (2000) Subtyping of uncultured bartonellae using sequence comparison of 16 S/23 S rRNA intergenic spacer regions amplified directly from infected blood. Molecular and Cellular Probes 14:2, 79-87
CrossRef111
Ciro Maguiña, Eduardo Gotuzzo. (2000) BARTONELLOSIS. Infectious Disease Clinics of North America 14:1, 1-22
CrossRef112
D.G. Pitcher, N.K. Fry. (2000) Molecular Techniques for the Detection and Identification of New Bacterial Pathogens. Journal of Infection 40:2, 116-120
CrossRef113
L Guptill. (1999) Immune response of neonatal specific pathogen-free cats to experimental infection with Bartonella henselae. Veterinary Immunology and Immunopathology 71:3-4, 233-243
CrossRef114
Francisco Rivera-Hidalgo, Thomas W. Stanford. (1999) Oral mucosal lesions caused by infective microorganisms I. Viruses and bacteria. Periodontology 2000 21:1, 106-124
CrossRef115
Ning Li, Amir Bajoghli, Asha Kubba, Jag Bhawan. (1999) Identification of mycobacterial DNA in cutaneous lesions of sarcoidosis. Journal of Cutaneous Pathology 26:6, 271-278
CrossRef116
Christopher P Kolbert, David H Persing. (1999) Ribosomal DNA sequencing as a tool for identification of bacterial pathogens. Current Opinion in Microbiology 2:3, 299-305
CrossRef117
Pierre-Edouard Fournier, Didier Raoult. (1999) Nonculture laboratory methods for the diagnosis of infectious endocarditis. Current Infectious Disease Reports 1:2, 136-141
CrossRef118
L. David Ormerod, J. P. Dailey. (1999) Ocular manifestations of cat-scratch disease. Current Opinion in Opthalmology 10:3, 209-216
CrossRef119
Janet Foley. (1999) Cooking with the Polymerase Chain Reaction. Journal of Veterinary Internal Medicine 13:3, 144-145
CrossRef120
Hermann J Girschick, Han-Iko Huppertz, Dag Harmsen, Rudiger Krauspe, Hans Konrad Müller-Hermelink, Thomas Papadopoulos. (1999) Chronic recurrent multifocal osteomyelitis in children: Diagnostic value of histopathology and microbial testing. Human Pathology 30:1, 59-65
CrossRef121
Charles R. Steinman. (1998) Broad-range bacterial polymerase chain reaction for identification of bacteria in inflamed joints: comment on the article by Wilbrink et al. Arthritis & Rheumatism 41:12, 2276-2278
CrossRef122
K Yamamoto. (1998) Homologous protection but lack of heterologous-protection by various species and types of Bartonella in specific pathogen-free cats. Veterinary Immunology and Immunopathology 65:2-4, 191-204
CrossRef123
Tracy I. George, Geoffrey Manley, Jane E. Koehler, Virginia S. Hung, Michael McDermott, Andrew Bollen. (1998) Detection of Bartonella henselae by polymerase chain reaction in brain tissue of an immunocompromised patient with multiple enhancing lesions. Journal of Neurosurgery 89:4, 640-644
CrossRef124
Nasimul Ahsan, Michael J. Holman, Thomas R. Riley, Catherine S. Abendroth, Erik G. Langhoff, Harold C. Yang. (1998) PELOISIS HEPATIS DUE TO BARTONELLA HENSELAE IN TRANSPLANTATION. Transplantation 65:7, 1000-1003
CrossRef125
David H. Spach, Jane E. Koehler. (1998) BARTONELLA-ASSOCIATED INFECTIONS. Infectious Disease Clinics of North America 12:1, 137-155
CrossRef126
A. C. Borczuk, G. Niedt, L. B. Sablay, Y. Kress, C. M. Mannion, S. M. Factor, K. E. Tanaka. (1998) Fibrous Long-Spacing Collagen in Bacillary Angiomatosis. Ultrastructural Pathology 22:2, 127-133
CrossRef127
J.E. Foley, B. Chomel, Y. Kikuchi, K. Yamamoto, N.C. Pedersen. (1998) Seroprevalence of Bartonella henselae in cattery cats: Association with cattery hygiene and flea infestation. Veterinary Quarterly 20:1, 1-5
CrossRef128
Anna Alanen. (1998) Polymerase chain reaction in the detection of microbes in amniotic fluid. Annals of Medicine 30:3, 288-295
CrossRef129
Koehler, Jane E., Sanchez, Melissa A., Garrido, Claudia S., Whitfeld, Margot J., Chen, Frederick M., Berger, Timothy G., Rodriguez-Barradas, Maria C., LeBoit, Philip E., Tappero, Jordan W., . (1997) Molecular Epidemiology of Bartonella Infections in Patients with Bacillary Angiomatosis–Peliosis. New England Journal of Medicine 337:26, 1876-1883
Full Text130
Tompkins, Lucy S., . (1997) Of Cats, Humans, and Bartonella. New England Journal of Medicine 337:26, 1916-1917
Full Text131
Michael F Minnick, Kent D Barbian. (1997) Identification of Bartonella using PCR; genus- and species-specific primer sets. Journal of Microbiological Methods 31:1-2, 51-57
CrossRef132
Dianne M. Heritz, Jean-Michel Y. Lacroix, Sukhsatej D. Batra, Keith A. Jarvi, B. Beheshti, Marc W. Mittelman. (1997) DETECTION OF EUBACTERIA IN INTERSTITIAL CYSTITIS BY 16S rDNA AMPLIFICATION. The Journal of Urology 158:6, 2291-2295
CrossRef133
Anna Sander, Bernhard Frank. (1997) Paronychia caused by Bartonella henselae. The Lancet 350:9084, 1078
CrossRef134
Pushker Raj. (1997) Molecular diagnosis of infectious diseases. The Indian Journal of Pediatrics 64:4, 435-440
CrossRef135
M. Maurin, R. Birtles, D. Raoult. (1997) Current knowledge ofBartonella species. European Journal of Clinical Microbiology & Infectious Diseases 16:7, 487-506
CrossRef136
D. A. Price, R. J. Birtles, T. S. Levine, J. Main, R. J. Coker. (1997) Bacillary angiomatosis. AIDS 11:9, 1186-1187
CrossRef137
Andrew H. Talal, Louis M. Weiss, Charles Vanderhorst. (1997) MOLECULAR DIAGNOSIS OF GASTROINTESTINAL INFECTIONS ASSOCIATED WITH HIV INFECTION. Gastroenterology Clinics of North America 26:2, 417-444
CrossRef138
Farida Hilali, Patrick Saulnier, Elisabeth Chachaty, Antoine Andremont. (1997) Decontamination of polymerase chain reaction reagents for detection of low concentrations of 16S rRNA genes. Molecular Biotechnology 7:3, 207-216
CrossRef139
Dittmar Hahn, Kornelia Zepp, Josef Zeyer. (1997) Whole cell hybridization as a tool to study Frankia populations in root nodules. Physiologia Plantarum 99:4, 696-706
CrossRef140
Akos Kovacs, Howard L. Leaf, Michael S. Simberkoff. (1997) BACTERIAL INFECTIONS. Medical Clinics of North America 81:2, 319-343
CrossRef141
Cabot, Richard C.Scully, Robert E., Mark, Eugene J., McNeely, William F., Ebeling, Sally H., Jacoby, George A.Hay, C. Mhorag. (1997) Case 2-1997. New England Journal of Medicine 336:3, 205-210
Full Text142
Rachel C. Abbott, Bruno B. Chomel, Rickie W. Kasten, Kim A. Floyd-Hawkins, Yoko Kikuchi, Jane E. Koehler, Niels C. Pedersen. (1997) Experimental and natural infection with Bartonella henselae in domestic cats. Comparative Immunology, Microbiology and Infectious Diseases 20:1, 41-51
CrossRef143
Kathleen J. Smith, Henry G. Skelton, Sylvana Tuur, Pamela L. Larson, Peter Angritt. (1996) Bacillary Angiomatosis in an Immunocompetent Child. The American Journal of Dermatopathology 18:6, 597-600
CrossRef144
J.J. McFadden, H.M. Fidler. (1996) Mycobacteria as possible causes of sarcoidosis and Crohn's disease. Journal of Applied Microbiology 81:s25, 47s-52s
CrossRef145
A. Christian Whelen, David H. Persing. (1996) THE ROLE OF NUCLEIC ACID AMPLIFICATION AND DETECTION IN THE CLINICAL MICROBIOLOGY LABORATORY 1. Annual Review of Microbiology 50:1, 349-373
CrossRef146
Robert C. Jerris, Russell L. Regnery. (1996) WILL THE REAL AGENT OF CAT-SCRATCH DISEASE PLEASE STAND UP? 1. Annual Review of Microbiology 50:1, 707-725
CrossRef147
H. -U. Schmidt, T. Kaliebe, J. Poppinger, C. Bühler, A. Sander. (1996) Isolation ofBartonella quintana from an HIV-positive patient with bacillary angiomatosis. European Journal of Clinical Microbiology & Infectious Diseases 15:9, 736-741
CrossRef148
Jean-Michel Lacroix, Keith Jarvi, Sukhsatej D. Batra, Dianne M. Heritz, Marc W. Mittelman. (1996) PCR-based technique for the detection of bacteria in semen and urine. Journal of Microbiological Methods 26:1-2, 61-71
CrossRef149
Steven M. Manders. (1996) Bacillary angiomatosis. Clinics in Dermatology 14:3, 295-299
CrossRef150
M Drancourt, R Birtles, D Raoult, G Chaumentin, F Vandenesch, J Etienne. (1996) New serotype of Bartonella heriselae in endocarditis and cat-scratch disease. The Lancet 347:8999, 441-443
CrossRef151
W. Schwartzman, M.D. (1996) BARTONELLA ( ROCHALIMAEA ) INFECTIONS: Beyond Cat Scratch 1. Annual Review of Medicine 47:1, 355-364
CrossRef152
Michel Dupon, Anne-marie Savin De Larclause, Philippe Brouqui, Michel Drancourt, Didier Raoult, Antoine De Mascarel, Jean-Yves Lacut. (1996) Evaluation of Serological Response to Bartonella henselae, Bartonella quintana and Afipia felis Antigens in 64 Patients with Suspected Cat-scratch Disease. Scandinavian Journal of Infectious Diseases 28:4, 361-366
CrossRef153
Elizabeth A. Wagar. (1996) Defining the unknown: Molecular methods for finding new microbes. Journal of Clinical Laboratory Analysis 10:6, 331-334
CrossRef154
John G. Guccion, Cynthia L. Gibert, Louis G. Ortega, Ted L. Hadfield. (1996) Cat Scratch Disease and Acquired Immunodeficiency Disease: Diagnosis by Transmission Electron Microscopy. Ultrastructural Pathology 20:3, 195-202
CrossRef155
G. Gaddnni, L. Baldassari, F. Pasi. (1996) Scattered skin lesions in cat scratch disease. Journal of the European Academy of Dermatology and Venereology 6:1, 80-80
CrossRef156
Jane E. Koehler, Laurie Cederberg. (1995) Intra-abdominal mass associated with gastrointestinal hemorrhage: A new manifestation of bacillary angiomatosis. Gastroenterology 109:6, 2011-2014
CrossRef157
H. BACHELEZ, E. OKSENHENDLER, C. LEBBE, C. DAUGA, L. PINQUIER, C. MAINGUENE, J.P. CLAUVEL, P.A.D. GRIMONT, P. MOREL, L. DUBERTRET, G. ARLET. (1995) Bacillary angiomatosis in HIV-infected patients: report of three cases with different clinical courses and identification of Rochalimaea quintana as the aetiological agent. British Journal of Dermatology 133:6, 983-989
CrossRef158
Lauren M. Pachman, Deborah L. Litt, Anne H. Rowley, Jennifer R. Hayford, Janice Caliendo, Scott Heller, Baruch S. Ticho, Mary Christensen, Bruce Patterson, Steven R. Ytterberg, Mark Pallansch. (1995) Lack of detection of enteroviral rna or bacterial dna in magnetic resonance imaging–directed muscle biopsies from twenty children with active untreated juvenile dermatomyositis. Arthritis & Rheumatism 38:10, 1513-1518
CrossRef159
Richard J. Birtles. (1995) Differentiation of Bartonella species using restriction endonuclease analysis of PCR-amplified 16S rRNA genes. FEMS Microbiology Letters 129:2-3, 261-265
CrossRef160
ANNIKA TIVELJUNG, JAN BACKSTRÖM, URBAN FORSUM, HANS-JÜRG MONSTEIN. (1995) Broad-range PCR amplification and DNA sequence analysis reveals variable motifs in 16S rRNA genes of Mobiluncus species. APMIS 103:7-8, 755-763
CrossRef161
Spach, David H., Kanter, Andrew S., Dougherty, Molly J., Larson, Ann M., Coyle, Marie B., Brenner, Don J., Swaminathan, Bala, Matar, Ghassan M., Welch, David F., Root, Richard K., Stamm, Walter E., . (1995) Bartonella (Rochalimaea) quintana Bacteremia in Inner-City Patients with Chronic Alcoholism. New England Journal of Medicine 332:7, 424-428
Full Text162
Drancourt, Michel, Mainardi, Jean Luc, Brouqui, Philippe, Vandenesch, François, Carta, Anne, Lehnert, Franck, Etienne, Jerome, Goldstein, Fred, Acar, Jacques, Raoult, Didier, . (1995) Bartonella (Rochalimaea) quintana Endocarditis in Three Homeless Men. New England Journal of Medicine 332:7, 419-423
Full Text163
Sulachni Chandwani, Aditya Kaul. (1995) Molecular techniques in biomedical sciences: A new era in diagnosis of infectious diseases. The Indian Journal of Pediatrics 62:1, 41-53
CrossRef164
Gareth P. Jevon, W. Michael Dunne, Milton J. Finegold. (1995) An Analysis of Lymph Node DNA for Possible Bacterial Agents of Cat-Scratch Disease. Fetal & Pediatric Pathology 15:1, 3-9
CrossRef165
Maria A. Paul, Alan B. Fleischer, Janet S. Wieselthier, Wain L. White. (1994) Bacillary Angiomatosis in an Immunocompetent Child: The First Reported Case. Pediatric Dermatology 11:4, 338-341
CrossRef166
S. C. A. CHEN, G. L. GILBERT. (1994) Cat scratch disease: Past and present. Journal of Paediatrics and Child Health 30:6, 467-469
CrossRef167
Lowsky, RobertArcher, Gordon L.Fyles, GillianMinden, MarkCurtis, JohnMessner, HansAtkins, HaroldPatterson, BruceWilley, Barbara M.McGeer, Allison. (1994) Diagnosis of Whipple's Disease by Molecular Analysis of Peripheral Blood. New England Journal of Medicine 331:20, 1343-1346
Full Text168
Raymond Ruimy, Violette Breittmayer, Valérie Boivin, Richard Christen. (1994) Assessment of the state of activity of individual bacterial cells by hybridization with a ribosomal RNA targeted fluorescently labelled oligonucleotidic probe. FEMS Microbiology Ecology 15:1-2, 207-213
CrossRef169
KL Hughes, JT Faragher. (1994) Cat scratch disease. Australian Veterinary Journal 71:8, 266-266
CrossRef170
Burt Anderson, Cynthia Goldsmith, Angela Johnson, Indira Padmalayam, Barbara Baumstark. (1994) Bacteriophage-like particle of Rochalimaea henselae. Molecular Microbiology 13:1, 67-73
CrossRef171
Adal, Karim A.Cockerell, Clay J.Petri, William A. Jr.. (1994) Cat Scratch Disease, Bacillary Angiomatosis, and Other Infections Due to Rochalimaea. New England Journal of Medicine 330:21, 1509-1515
Full Text172
Bethi Muralidhar, Peter M. Rumore, Charles R. Steinman. (1994) Use of the polymerase chain reaction to study arthritis due toneisseria gonorrhoeae. Arthritis & Rheumatism 37:5, 710-717
CrossRef173
J.F. Schellekens. (1994) Cat scratch disease. Veterinary Quarterly 16:sup1, 11-12
CrossRef174
I. Kempf, F. Gesbert, M. Guittet, G. Bennejean. (1994) Mycoplasma gallisepticum Infection in Drug-treated Chickens: Comparison of Diagnosis Methods Including Polymerase Chain Reaction. Journal of Veterinary Medicine, Series B 41:1-10, 597-602
CrossRef175
M. Drancourt, D. Raoult. (1994) Taxonomic position of the Rickettsiae: Current knowledge. FEMS Microbiology Reviews 13:1, 13-24
CrossRef176
T.L. Hadfield, R. Warren, M. Kass, E. Brun, C. Levy. (1993) Endocarditis caused by Rochalimaea henselae. Human Pathology 24:10, 1140-1141
CrossRef177
Zangwill, Kenneth M.Hamilton, Douglas H.Perkins, Bradley A.Regnery, Russell L.Plikaytis, Brian D.Hadler, James L.Cartter, Matthew L.Wenger, Jay D.. (1993) Cat Scratch Disease in Connecticut -- Epidemiology, Risk Factors, and Evaluation of a New Diagnostic Test. New England Journal of Medicine 329:1, 8-13
Full Text178
(1993) Isolation of Rochalimaea Species. New England Journal of Medicine 328:19, 1422-1423
Full Text179
Michael Glick, Deborah B. Cleveland. (1993) Oral mucosal bacillary epithelioid angiomatosis in a patient with AIDS associated with rapid alveolar bone loss: case report. Journal of Oral Pathology and Medicine 22:5, 235-239
CrossRef180
Hofer, MichaelHirschel, BernardKirschner, PhilipBeghetti, MauriceKaelin, AndreSiegrist, Clair-AnneSuter, SusanneTeske, AndreasBottger, Erik C.. (1993) Disseminated Osteomyelitis from Mycobacterium ulcerans after a Snakebite. New England Journal of Medicine 328:14, 1007-1009
Full Text181
D. INNOCENZI, R. CERIO, O. BARDUAGNI, C. BOSMAN, O. A. CARLESIMO. (1993) Bacillary epithelioid angiomatosis in acquired immunodeficiency syndrome (AIDS)-clinicopathological and ultrastructural study of a case with a review of the literature. Clinical and Experimental Dermatology 18:2, 133-137
CrossRef182
David H. Persing. (1993) Diagnostic molecular microbiology current challenges and future directions. Diagnostic Microbiology and Infectious Disease 16:2, 159-163
CrossRef183
(1993) Identification of the Whipple's Disease Bacillus. New England Journal of Medicine 328:1, 62-63
Full Text184
Koehler, Jane E., Quinn, Frederick D., Berger, Timothy G., LeBoit, Philip E., Tappero, Jordan W., . (1992) Isolation of Rochalimaea Species from Cutaneous and Osseous Lesions of Bacillary Angiomatosis. New England Journal of Medicine 327:23, 1625-1631
Full Text185
(1992) Case 22-1992: Pathogenesis of Cat Scratch Disease. New England Journal of Medicine 327:22, 1599-1601
Full Text186
Desforges, Jane F., , Tompkins, Lucy S., . (1992) The Use of Molecular Methods in Infectious Diseases. New England Journal of Medicine 327:18, 1290-1297
Full Text187
MICHAEL STÜRZL, HEINZ BRANDSTETTER, WILLY KURT ROTH. (1992) Kaposi's Sarcoma: A Review of Gene Expression and Ultrastructure of KS Spindle Cells In Vivo. AIDS Research and Human Retroviruses 8:10, 1753-1763
CrossRef188
Russell Regnery, Marie Martin, James Olson. (1992) Naturally occurring "Rochalimaea henselae" infection in domestic cat. The Lancet 340:8818, 557-558
CrossRef189
Relman, David A., Schmidt, Thomas M., MacDermott, Richard P., Falkow, Stanley, . (1992) Identification of the Uncultured Bacillus of Whipple's Disease. New England Journal of Medicine 327:5, 293-301
Full Text190
David A. Relman, Paul W. Lepp, Kay N. Sadler, Thomas M. Schmidt. (1992) Phylogenetic relationships among the agent of bacillary angiomatosis, Bartonella bacilliformis, and other alpha-proteobacteria. Molecular Microbiology 6:13, 1801-1807
CrossRef191
R.L Regnery, J.G Olson, B.A Perkins, W Bibb. (1992) Serological response to "Rochalimaea henselae" antigen in suspected cat-scratch disease. The Lancet 339:8807, 1443-1445
CrossRef192
Phillips, Tania J., Dover, Jeffrey S., . (1992) Recent Advances in Dermatology. New England Journal of Medicine 326:3, 167-178
Full Text193
Jan Marc Orenstein. (1992) Ultrastructural Pathology of Human Immunodeficiency Virus Infection. Ultrastructural Pathology 16:1-2, 179-210
CrossRef194
Mery Kostianovsky, Maj Yvonne Lamy, M. Alba Greco. (1992) Immunohistochemical and Electron Microscopic Profiles of Cutaneous Kaposi's Sarcoma and Bacillary Angiomatosis. Ultrastructural Pathology 16:6, 629-640
CrossRef195
W. Liesack, E. Stackebrandt. (1992) Unculturable microbes detected by molecular sequences and probes. Biodiversity and Conservation 1:4, 250-262
CrossRef196
DAVID H. SPACH. (1992) BACILLARY ANGIOMATOSIS. International Journal of Dermatology 31:1, 19-24
CrossRef197
(1991) The Causative Agent of Bacillary Angiomatosis. New England Journal of Medicine 325:20, 1447-1448
Full Text198
Gerri S. Hall, Kathy Pratt-Rippin, John A. Washington. (1991) Isolation of agent associated with cat scratch disease bacillus from pretibial biopsy. Diagnostic Microbiology and Infectious Disease 14:6, 511-513
CrossRef199
(1991) Proceedings of the 256th meeting of the Netherlands Society for Dermatology and Venereology, Amsterdam, 20 April 1991. British Journal of Dermatology 125:4, 390-399
CrossRef200
(1991) The Agent of Bacillary Angiomatosis. New England Journal of Medicine 324:21, 1511-1513
Full Text201
(1991) The Organism Causing Bacillary Angiomatosis, Peliosis Hepatis, and Fever and Bacteremia in Immunocompromised Patients. New England Journal of Medicine 324:21, 1514-1514
Full Text202
Marjut Ranki. (1991) New Microbial Diagnosis. Annals of Medicine 23:4, 381-388
CrossRef203
Eisenstein, Barry I., . (1990) New Opportunistic Infections — More Opportunities. New England Journal of Medicine 323:23, 1625-1627
Full Text204
(1990) Rickettsia-like opportunistic agent. The Lancet 336:8729, 1501
CrossRef
- Letters
