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Biomedical subjects

A P Hudson

Publications and source records attributed to A P Hudson.

At least 19 recordsLinked to original sources
PubMed2000

Detection of Chlamydia pneumoniae in giant cell vasculitis and correlation with the topographic arrangement of tissue-infiltrating dendritic cells.

OBJECTIVE: Recent studies suggest that giant cell arteritis (GCA) may be an antigen-driven disease. Since Chlamydia pneumoniae has been identified in arterial vessel walls, it was hypothesized that this organism might be associated with GCA. METHODS: Fourteen paraffin-embedded temporal artery biopsy specimens from 9 patients with GCA were examined by immunohistochemistry and by polymerase chain reaction (PCR) for the presence of C pneumoniae; for 5 patients, specimens were available from both the left and right arteries. Four temporal artery specimens from 3 patients with polymyalgia rheumatica (PMR) and 9 temporal artery specimens from 5 patients without GCA or PMR served as controls. RESULTS: C pneumoniae was detected by both immunohistochemistry and PCR in 6 GCA patient samples. One GCA patient sample was immunopositive only; another was PCR positive only. Thus, C pneumoniae was found in 8 of 9 GCA patients. One of 4 control samples from the PMR patients was immunopositive, but PCR negative, for C pneumoniae. The C pneumoniae-positive PMR patient also had respiratory symptoms. The remaining 9 control samples were negative for C pneumoniae by both immunohistochemistry and PCR. Immunohistochemistry showed that bacteria predominate in the adventitial layer of temporal arteries, in granulomatous infiltrates. Dendritic cells were examined by immunohistochemistry for their presence and localization in consecutive temporal artery specimens, and showed a strong topographic relationship with C pneumoniae. Like the bacterium, dendritic cells predominate in the adventitial layer of the arteries. CONCLUSION: C pneumoniae was found in temporal artery specimens from most GCA patients, in 1 specimen from a PMR patient, and in no other control specimens; thus, it may play a role in the pathogenesis of the disease. Dendritic cells may represent the antigen-presenting cells in this situation.

Aged↗
PubMed2000

Chlamydia pneumoniae present in the human synovium are viable and metabolically active.

We demonstrated that chromosomal DNA from Chlamydia pneumoniae is present in synovial tissue in at least some patients with reactive arthritis/Reiter's syndrome and other arthritides. Here, we provide initial molecular evidence that the bacterium is viable and metabolically active when present in the synovium. We used reverse transcription-polymerase chain reaction (RT-PCR) assays targeting primary transcripts from the chlamydial rRNA operons, and mRNA from several C. pneumoniae genes (hsp60, ompA, KDO transferase, Mr=76000 protein), to analyse RNA preparations from synovial tissue of 10 patients with various forms of arthritis; each patient was known to be PCR-positive for C. pneumoniae DNA in synovium prior to RT-PCR assays. Two PCR-negative patients served as controls for RT-PCR assays. In the 10 patients PCR-positive for C. pneumoniae DNA, RT-PCR assays targeting primary transcripts from the rRNA operons of the organism showed that these molecules were present in each sample, as were transcripts from the bacterial hsp60 gene. Assays targeting mRNAs from the Mr=76000 protein and the KDO transferase genes of C. pneumoniae gave positive results for 6/10 preparations. We were unable to identify mRNA from the chlamydial major outer membrane protein gene (ompA) in any preparation. RNA preparations from the two control patients were negative in all RT-PCR assays targeting C. pneumoniae transcripts. These results indicate that in patients infected with the organism, synovial C. pneumoniae are viable and metabolically active, as are C. trachomatis cells in the same context. Such viability is consistent with a role in long-term contribution to pathogenesis in joint disease.

Adult↗
PubMed2000

Reactive arthritis: preliminary microbiologic analysis of the human temporomandibular joint.

PURPOSE: The presence of Chlamydia trachomatis has been previously shown in the temporomandibular joint (TMJ). This study investigated whether the presence of other bacteria associated with reactive arthritis (ReA) can be identified in the TMJ. MATERIALS AND METHODS: Posterior bilaminar tissue removed during TMJ surgery from 26 patients (24 F, 2 M) was evaluated for the presence of C. trachomatis, Mycoplasma fermentans, Mycoplasma genitalium, Campylobacter jejuni, Yersinia enterocolitica, Salmonella spp, and Shigella spp by highly specific polymerase chain reaction (PCR) assays. RESULTS: Bacterial DNA was identified in the TMJ as follows: C. trachomatis, 11 of 26 (42%); M. fermentans/orale, 6 of 26 (23%); M. genitalium, 9 of 26 (35%). Nine of 26 TMJs (35%) had the presence of a single bacterial species. Eight of 26 TMJs (31%) had more than 1 species, as follows: C. trachomatis with either M. genitalium or M. fermentans/orale in 5 of 26 (19%), M. fermentans/orale with M. genitalium 2 of 26 (8%), and C. trachomatis/M. fermentans/orale/M. genitalium, 1 of 26 (4%). A total of 17 of 26 (65%) of TMJs had the presence of bacteria identified in the TMJ. Campylobacter jejuni, Y. enterocolitica, Salmonella spp, and Shigella spp were not identified in any samples. CONCLUSIONS: The presence of M. genitalium in the human TMJ has not been previously reported. The presence of bacteria in the TMJ, either singly or concurrently with other bacteria, may serve as the pathogenetic mechanism of TMJ inflammation. The presence of 2 bacteria from the urogenital tract in the TMJ suggests that internal derangement of the TMJ may occur as a result of a sexually acquired infection.

Adolescent↗
PubMed2000

Rapid communication: Cervical Chlamydia trachomatis in women at low risk for infection.

BACKGROUND: Evidence suggests that the bacterium Chlamydia trachomatis can cause asymptomatic genital infection in persons at risk for acquisition of the organism. We employed 2 independent molecular screening systems to assess such inapparent cervical chlamydial infections in low-risk female patients attending general (non-STD) clinics in 2 locations. METHODS: Three hundred seventy-five cervical swab samples were obtained in duplicate from patients attending a general women's clinic (278 samples) and a colposcopy clinic (97 samples). One set of samples from the general clinic was screened by a highly-specific molecular hybridization system, using a probe targeting the chlamydial 16S ribosomal RNA; the other set was screened with the use of the Chlamydiazyme test. Samples from the colposcopy clinic were screened using a sensitive and specific polymerase chain reaction (PCR) assay system targeting chlamydia; the duplicates were assayed by direct fluorescent antibody assay (DFA). RESULTS: Of the 278 patients screened by RNA-directed hybridization, 6.5% were positive for C. trachomatis, in contrast to screening of duplicate samples via Chlamydiazyme, which indicated that 3.6% were infected. PCR-based screening of the additional 97 patients gave a positivity rate of 17.5% for the organism, whereas DFA on duplicate samples from this group showed only 7.5% positive. CONCLUSIONS: These observations suggest that the level of asymptomatic cervical C. trachomatis infection is significant even in women who are at low risk for such infections; the data also indicate that results from standard laboratory screening for chlamydia should be viewed with caution.

Adolescent↗
PubMed2000

Chlamydia and associated arthritis.

An inflammatory arthritis is known to follow urogenital infection with the intracellular bacterium Chlamydia trachomatis in some individuals, and recent research results have elucidated important aspects of the characteristics of this Chlamydia-associated joint disease. Although the several extra-articular features of Chlamydia-induced arthritis have been defined clinically, their detailed causes remain largely unexplained. Current data indicate that the clinical characteristics of joint disease associated with C. trachomatis infection and those associated with postenteric arthritis are not easily distinguishable, although the response of each to antibiotic therapy does differ. The biologic characteristics of Chlamydia and enteric organisms in the joint show profound differences, and these are probably responsible for the variable responses to drug treatment. Molecular analyses of synovial C. trachomatis have demonstrated that long-term infection of the joint occurs primarily in synovial tissue and that the organism exhibits highly unusual biologic properties in its synovial context. These unusual molecular, biochemical, and other characteristics provide explanations for the frequent culture negativity of joint materials for C. trachomatis and for several other aspects of the arthritogenic process. Much remains to be learned concerning the behavior of this organism in the joint and concerning its interaction with its synovial host cells.

Anti-Bacterial Agents↗
PubMed2000

Persistence of Chlamydia trachomatis is induced by ciprofloxacin and ofloxacin in vitro.

An in vitro cell culture model was used to investigate the long-term effect of ciprofloxacin and ofloxacin on infection with Chlamydia trachomatis. Standard in vitro susceptibility testing clearly indicated successful suppression of chlamydial growth. To mimic better in vivo infection conditions, extended treatment with the drugs was started after infection in vitro had been well established. Incubation of such established chlamydial cultures with ciprofloxacin and ofloxacin not only failed to eradicate the organism from host cells, but rather induced a state of chlamydial persistence. This state was characterized by the presence of nonculturable, but fully viable, bacteria and the development of aberrant inclusions. In addition chlamydia exhibited altered steady-state levels of key chlamydial antigens, with significantly reduced major outer membrane protein and near constant hsp60 levels. Resumption of overt chlamydial growth occurred after withdrawal of ciprofloxacin, confirming the viability of persisting chlamydia. In vitro ciprofloxacin results are consistent with clinical data, thereby providing an explanation for treatment failures of ciprofloxacin. Parallel in vitro studies with ofloxacin suggest a better correlation between clinical and laboratory-defined efficacy, although the clinical studies on which this assessment is based did not include monitoring of chlamydial persistence. The data presented here clearly demonstrate that under at least some circumstances, standard determination of MICs and minimal bactericidal concentrations for C. trachomatis allows no more than a simple definition of whether an antibiotic has some anti chlamydial activity; however, such testing is not always sufficient to verify that the antibiotic will eliminate the organism in vivo.

Anti-Infective Agents↗
PubMed1999

Chlamydia trachomatis nucleic acids can be found in the synovium of some asymptomatic subjects.

OBJECTIVE: The recent identification of antigens or nucleic acids of infectious agents in the joints of patients with reactive arthritis has raised questions about whether chlamydial or other infectious agent nucleic acids are also present in normal joints. We had the opportunity to study synovium from 30 asymptomatic volunteer subjects by use of polymerase chain reaction (PCR) for attempted identification of Chlamydia and other infectious agents. METHODS: All subjects had blind needle synovial biopsies with the Parker-Pearson needle. DNA was extracted and PCR performed using primers for Chlamydia trachomatis, Chlamydia pneumoniae, Borrelia burgdorferi, and pan bacterial 16S ribosomal RNA (rRNA). RESULTS: Two subjects were identified with nucleic acid for the 16S rRNA gene of C trachomatis. All other PCR reactions were negative except for the pan bacterial 16S rRNA in the C trachomatis-positive subjects. Both subjects, although symptom free, had some evidence of synovial reaction. CONCLUSION: C trachomatis appears to occasionally be disseminated to joints without producing overt disease.

Adult↗
PubMed1999

Lower prevalence of Chlamydia pneumoniae DNA compared with Chlamydia trachomatis DNA in synovial tissue of arthritis patients.

OBJECTIVE: To assess the presence of Chlamydia pneumoniae DNA in the joints of patients with reactive arthritis (ReA) and other arthritides. METHODS: DNA was prepared from synovial tissue (ST) and several synovial fluid (SF) samples from 188 patients with either ReA, undifferentiated oligoarthritis, or other forms of arthritis, and from 24 normal (non-arthritis) individuals. Preparations were screened using polymerase chain reaction (PCR) assays that independently targeted the C. pneumoniae 16S ribosomal RNA and major outer membrane protein genes. RESULTS: Twenty-seven of 212 ST samples (12.7%) were PCR positive for C. pneumoniae DNA; 10 SF samples from these 27 patients were similarly positive. Among the PCR-positive patients, 3 had ReA, 2 had Reiter's syndrome, 7 had undifferentiated oligoarthritis, 4 had undifferentiated monarthritis, 6 had rheumatoid arthritis, and 5 had other forms of arthritis. No samples from normal control individuals were PCR positive. CONCLUSION: DNA of C pneumoniae is present in synovial specimens from some arthritis patients. The prevalence of this organism in the joints was lower than that of C trachomatis, and synovial presence of the organism was not associated with any distinct clinical syndrome. Widely disseminated nucleic acids such as those of C. pneumoniae might have some role in the pathogenesis of several arthritides, since the organism was not found in the ST from normal control individuals.

Arthritis, Reactive↗
PubMed1999

Frequency of apolipoprotein E (APOE) allele types in patients with Chlamydia-associated arthritis and other arthritides.

Genetic background is important in determining whether certain infecting bacteria disseminate to the joint and cause arthritis. We assessed whether APOE genotype is associated with the presence of DNA from Chlamydia or other bacteria in synovial tissues of patients with various arthritides. Nucleic acids from synovial tissues of 135 patients were screened by PCR for DNA from Chlamydia trachomatis, C. pneumoniae and other bacteria (pan-bacteria). APOE genotype was determined by a PCR-based method for all patients in each of four resulting groups comprised of about 35 individuals each, positive for C. trachomatis only, C. pneumoniae only, other bacteria, or no bacteria. RT-PCR was used to assess synovial APOE expression. The latter assays confirmed that APOE mRNA is present in synovial tissue. Determination of APOE genotype showed that patients PCR-negative in all assays, and those positive in the C. trachomatis - and pan-bacteria- (excluding Chlamydia) directed assays, had distributions of the APOE epsilon2, epsilon3 and epsilon4 alleles mirroring those of the general population (i.e. about 8%, 79% and 13%, respectively). In contrast, 68% of patients with C. pneumoniae DNA in synovium possessed a copy of the epsilon4 allele. These results indicate that no association exists between APOE genotype and synovial presence of C. trachomatis or other bacteria. However, individuals bearing at least one copy of the APOE epsilon4 allele may be at increased risk for synovial infection by C. pneumoniae.

Alleles↗
PubMed1999

Identification of Chlamydia trachomatis in the human temporomandibular joint.

PURPOSE: Reactive arthritis (ReA) as a consequence of triggering Chlamydia trachomatis infections has been extensively studied to better understand inflammatory arthritis. This study investigated whether the presence of C trachomatis can be shown in the TMJ of patients with internal derangement. PATIENTS AND METHODS: Posterior bilaminar tissue removed from 31 patients (29 F, 2 M) during TMJ articular disc repositioning and posterior ligament repair was tested for the presence of C trachomatis. Cryosections were stained using a monoclonal antibody that identifies all chlamydial serovars. Highly specific polymerase chain reaction (PCR) assays independently targeting two genes of C trachomatis also were performed; these assays also identify all serovars of this organism. RESULTS: TMJ tissue from 6 of 30 patients (20%) showed the presence of C trachomatis in the posterior bilaminar tissue on immunostaining. PCR screening identified 12 of 31 patients (39%) as having C trachomatis DNA in tissue, including four of six positive by immunostaining. All chlamydia-positive patients were female, with an average age of 36.7 years (15 to 48 years). CONCLUSIONS: The presence of C trachomatis in the human TMJ has not been previously shown. The presence of this organism may serve as the pathogenetic mechanism for TMJ dysfunction, as demonstrated in other joints. Nonapparent chlamydial infection in females may also explain the marked prevalence of TMJ symptoms in women.

Adolescent↗
PubMed1999

Mitochondrial and mitochondrial-related nuclear genetic function in rabbit urinary bladder following reversal of outlet obstruction.

Partial outlet obstruction of the rabbit urinary bladder causes increased tissue hypertrophy and decreased contractility of that organ; we showed that, in an experimental rabbit model, both correlate closely with alterations in the status and expression of mitochondrial (mt), and mt-related nuclear, genetic parameters in bladder smooth muscle. Here we investigate the rate and overall level of recovery of mt and nuclear genetic function following reversal of outlet obstruction in the same animal model. Release from outlet obstruction at 28 days resulted in improvement in both level of hypertrophy and contractile function in all bladders studied. However, bladders fell into two groups based on whether relative copy mt genome number per cell was above or below that of unobstructed controls. Bladders with high mt DNA content adjusted organellar genome copy number toward normal post-reversal but did not properly adjust mt transcript levels; mt-related nuclear transcripts in these samples showed recovery. Bladders with low mt DNA content showed no adjustment of those levels toward normal post-reversal but did show some adjustment in other mt and nuclear genetic parameters. Thus, a limiting factor for return of normal bladder function following reversal of outlet obstruction may be recovery of normal mt genetic performance.

Animals↗
PubMed1999

Mitochondrial involvement in bladder function and dysfunction.

Benign bladder pathology resulting from prostatic hypertrophy or other causes is a significant problem associated with ageing in humans. This condition is characterized by increased bladder mass, decreased urinary flow rate, decreased compliance, and these and other changes in bladder function often subject patients to increased risk of urinary tract infection. While the physiologic attributes of benign bladder pathology have been extensively described in humans and in various animal model systems, the biochemical and molecular genetic bases for that pathology have only recently been investigated in detail. Studies demonstrate that mitochondrial energy production and utilization are severely impaired in bladder smooth muscle during benign bladder disease, and to a large extent this realization has provided a rational basis for understanding the characteristic alterations in urinary flow and compliance in bladder tissue. Recent investigations targeting the detailed molecular basis for impaired mitochondrial function in the disease have shown that performance of the organellar genetic system, and to a large extent that of relevant portions of the nuclear genetic system as well, is severely aberrant in bladder tissue. In this article, we discuss the physiologic aspects of benign bladder disease, summarize biochemical evidence for the altered mitochondrial energy metabolism that appears to underlie bladder pathology, review the structure and function of the mitochondrial genetic system, and discuss molecular genetic studies of that system which have begun to provide a mechanistic explanation for the biochemical and physiological abnormalities that characterize the disease. We also discuss areas for further research which will be critically important in increasing our understanding of the detailed causes of benign bladder pathology.

Aging↗
PubMed1999

Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers.

Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN-gamma) responses in mice correlate with clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN-gamma and additional cytokine genes in patients who had recent-onset Chlamydia-associated arthritis (Chl-AA). IL-10 and IFN-gamma mRNA were relatively abundant in recent-onset Chl-AA.

Adult↗
PubMed1998

Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain.

We assessed whether the intracellular bacterium Chlamydia pneumoniae was present in post-mortem brain samples from patients with and without late-onset Alzheimer's disease (AD), since some indirect evidence seems to suggest that infection with the organism might be associated with the disease. Nucleic acids prepared from those samples were screened by polymerase chain reaction (PCR) assay for DNA sequences from the bacterium, and such analyses showed that brain areas with typical AD-related neuropathology were positive for the organism in 17/19 AD patients. Similar analyses of identical brain areas of 18/19 control patients were PCR-negative. Electron- and immunoelectron-microscopic studies of tissues from affected AD brain regions identified chlamydial elementary and reticulate bodies, but similar examinations of non-AD brains were negative for the bacterium. Culture studies of a subset of affected AD brain tissues for C. pneumoniae were strongly positive, while identically performed analyses of non-AD brain tissues were negative. Reverse transcription (RT)-PCR assays using RNA from affected areas of AD brains confirmed that transcripts from two important C. pneumoniae genes were present in those samples but not in controls. Immunohistochemical examination of AD brains, but not those of controls, identified C. pneumoniae within pericytes, microglia, and astroglia. Further immunolabelling studies confirmed the organisms' intracellular presence primarily in areas of neuropathology in the AD brain. Thus, C. pneumoniae is present, viable, and transcriptionally active in areas of neuropathology in the AD brain, possibly suggesting that infection with the organism is a risk factor for late-onset AD.

Aged↗
PubMed1998

Viability and gene expression in Chlamydia trachomatis during persistent infection of cultured human monocytes.

The principal host cell for persistently infecting synovial Chlamydia trachomatis is the macrophage. During infection of human monocytes/macrophages in culture this bacterium displays aberrant morphology and produces no new elementary bodies, reflecting the situation in synovium. Here we investigate the metabolic status of C. trachomatis (serovar K) during an extended infection of human peripheral monocytes in vitro. Using reverse transcription-polymerase chain reaction assays, we have shown that primary transcripts from the chlamydial rRNA operons are present throughout a 10-day course of infection. Other assays targeting mRNAs from chlamydial genes encoding r-proteins S5 and L5, the glycyl-tRNA synthetase, the 60-kDa cysteine-rich outer membrane protein, and the KDO transferase indicate that these messengers are also present throughout the entire 10-day period. The gene encoding the 57-kDa heat-shock protein (hsp60) is expressed by the bacterium throughout the 10-day infection of cultured monocytes, but transcript levels from the gene encoding the major outer membrane protein (omp1) appear to be attenuated. Western analyses targeting these latter proteins confirm the presence of the hsp60 gene product, and the virtual absence of major outer membrane protein, in chlamydia-infected cultured human monocytes. Thus, during extended infection of human monocytes in vitro, chlamydia are non-productive but transcriptionally active; the pattern of transcriptional activity reflects that known for persistent C. trachomatis infection in vivo in synovial tissue.

Antibodies, Monoclonal↗
PubMed1998

Viability of Chlamydia trachomatis in fallopian tubes of patients with ectopic pregnancy.

OBJECTIVE: To use standard molecular methods to define the prevalence and metabolic characteristics of Chlamydia trachomatis during infection of fallopian tubes in women with ectopic pregnancies. DESIGN: Polymerase chain reaction (PCR)- and reverse transcription-PCR (RT-PCR)-based assessment of presence of chlamydial DNA and various RNA species in fallopian tube biopsy samples. SETTING: Hospital and molecular genetics laboratory. PATIENTS: Ten women of varying ages, each presenting with ectopic pregnancy. MAIN OUTCOME MEASURE(S): Positive signal in specific chlamydia-directed PCR and RT-PCR assays. RESULT(S): Nucleic acid preparations from 7 of the 10 fallopian tube patient samples were PCR-positive for C. trachomatis DNA. Each of the 7 PCR-positive samples also showed the presence of several transcripts from the bacterium, including primary transcripts from the ribosomal RNA operons. CONCLUSION(S): A higher proportion of ectopic pregnancies than was believed previously may be attributable to infection of the fallopian tubes by C. trachomatis. The presence of various chlamydial RNA molecules suggests that viable, metabolically active bacteria were present in fallopian tubes of the patients studied.

Adult↗
PubMed1998

Aetiological agents: their molecular biology and phagocyte-host interaction.

Inflammatory joint disease can develop following an extra-articular infection. The term reactive arthritis was coined in order to differentiate this arthritis, which is often characterized by lack of culturable organisms in the joint, from septic arthritides. Bacteria known to trigger reactive arthritis include Campylobacter, Chlamydia, Salmonella, Shigella and Yersinia. Demonstration of bacteria or bacterial macromolecules in the joint has elicited the idea that reactive arthritis is a sterile process induced and maintained by antigenic material in the synovium. Continued synthesis of antigens to maintain synovial inflammation probably requires establishment of persistent bacterial infection in the joint, or at the primary site of infection. In the case of Chlamydia trachomatis, viable, metabolically-active organisms have been demonstrated to exist for extended periods in the joints of patients with reactive arthritis. In this chapter, we review the aetiological agents, and their molecular biology and phagocyte-host interactions, that are involved in reactive arthritis and spondylarthropathy.

Arthritis, Reactive↗