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Biomedical subjects

C C Kuo

Publications and source records attributed to C C Kuo.

At least 91 records · Page 5Linked to original sources

Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen.

Chlamydia pneumoniae has been associated with atherosclerotic cardiovascular disease by both seroepidemiologic studies and direct detection of the organism in atherosclerotic plaque by electron microscopy (EM), immunocytochemistry (ICC), and polymerase chain reaction (PCR). Despite the frequent detection of the organism in atheromatous cardiovascular specimens by these methods, only 1 cardiovascular isolate of C. pneumoniae, obtained from a coronary artery, has been previously reported. This study reports the isolation of C. pneumoniae from a prospectively obtained carotid endarterectomy specimen. The organism appears to be identical to other C. pneumoniae isolates by EM morphology, reactivity to species-specific monoclonal antibodies, and Southern hybridization analysis of chromosomal digests using C. pneumoniae-specific DNA probes. C. pneumoniae was detected by PCR or ICC (or both) in 11 (69%) of 16 other endarterectomy specimens tested by both of these methods. These results provide further evidence for an association of C. pneumoniae and atherosclerosis by confirming the presence of viable bacteria within atherosclerotic plaque.

Chlamydophila pneumoniae↗

Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytoin and possible therapeutic implications.

Carbamazepine and phenytoin, two of the most commonly prescribed antiepileptic drugs, have been proposed to share a similar mechanism of action by use-dependent inhibition of Na+ channels. The proposed similar mechanism of action, however, cannot explain the common clinical experiences that the two drugs are different; in some patients, one drug may be more effective than the other. This may occur even when optimal therapeutic concentrations are reached with both medications in plasma or the cerebrospinal fluid. In this study, we show that the action of the two drugs on Na+ channels are quantitatively very different. The affinity between inactivated Na+ channels and carbamazepine (apparent dissociation constant approximately 25 microM) is approximately 3 times lower than that of phenytoin, yet the binding rate constant of carbamazepine onto the inactivated Na+ channels is approximately 38,000 M(-1)/sec(-1), or approximately 5 times faster than that of phenytoin. It is speculated that carbamazepine may be more effective than phenytoin in treating seizures whose ictal depolarization shift is relatively short, whereas a better response to phenytoin may imply abnormal discharges characterized by more prolonged depolarization.

Animals↗

Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes produces a Th1-like cytokine response associated with fibrosis and scarring.

Chlamydia trachomatis-associated female infertility and ectopic pregnancy are caused by postinflammatory fibrosis and scarring of the upper genital tract. Scarring of the upper genital tract is associated with multiple infectious episodes with C. trachomatis. To study the immune response that occurs with multiple infections of C. trachomatis in the female upper genital tract, a Macaca nemestrina model was used. Subcutaneous pockets containing autologous salpingeal tissue implants were inoculated three times with C. trachomatis. The inflammation after three inoculations was associated with a mononuclear infiltrate dominated by CD8 T-cell lymphocytes. Perforin mRNA was induced in infected pockets, demonstrating that activated cytolytic lymphocytes were present in the lesions. Fibrosis, as evidenced by fibroblast proliferation and connective tissue deposition, was observed by the third infection. Cytokine mRNAs induced by repeated chlamydial infection included gamma interferon, interleukin-2 (IL-2), IL-6, and IL-10 mRNAs, but IL-4 mRNA was not induced. Nearly identical findings were found in macaque fallopian tubes infected in situ repeatedly with C. trachomatis, validating the subcutaneous pocket model of chlamydial salpingitis. However, it was not possible to evaluate if there was an induction of perforin mRNA in infected salpingeal tubes in situ, because there was a high basal level of perforin mRNA in these tissues. These results suggest that repeated chlamydial infection of the female upper genital tract leads to CD8 T-cell predominance, a Th1-like cytokine milieu, and these inflammatory changes are associated with progression to fibrosis associated with female infertility.

Animals↗

Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis.

Chlamydia pneumoniae has been detected in atherosclerotic plaque, raising the question of whether this detection is specific to atheromatous tissue. To evaluate this question, we tested cardiovascular and non-cardiovascular tissue samples from 38 autopsy cases by polymerase chain reaction and immunocytochemistry. We also tested 33 granuloma biopsy specimens, as the organism has been detected in macrophages. C. pneumoniae was detected in coronary artery tissue from 13 (34%), lung from 5 (13%), liver from 4 (10%), and spleen from 2 (5%) of the 38 autopsy cases (P < 0.05 for comparison of proportion of positive coronary arteries with that of each of the other types of tissue). Of the 21 cases with at least one positive tissue sample, 11 had only a positive cardiovascular tissue (coronary artery, venous bypass graft, or myocardium), 7 had both cardiovascular and non-cardiovascular positive tissues, and 3 had only a non-cardiovascular positive tissue. C. pneumoniae was thus detected relatively infrequently in non-cardiovascular tissues, and its detection in these tissues was usually in association with its detection in cardiovascular tissue from the same patient. The organism was also infrequently detected in granulomatous tissue (3/33 specimens). These findings demonstrate that C. pneumoniae is more frequently found in atherosclerotic than normal tissue and support the hypothesis that C. pneumoniae has a role in the pathogenesis of atherosclerosis.

Adolescent↗

The 18-kDa lectin-binding protein of Chlamydia trachomatis is different from the 18-kDa histone-like protein.

Five proteins of Chlamydia trachomatis at the 18,000 (18-kDa) molecular mass region were resolved by two-dimensional electrophoresis. Three proteins at 18.2 kDa, pI 6.9, 18.0 kDa, pI 6.3, and 17.9 kDa, pI 6.4 were shown to bind lectin. A fourth protein of 18.0 kDa at pI 10 was the histone-like protein. The fifth protein at 17.9 kDa, pI 7.0 was not characterized.

Bacterial Proteins↗

Serological response to Chlamydia pneumoniae in patients with sarcoidosis.

The antigen-specific serological response to Chlamydia pneumoniae was studied in 24 patients with sarcoidosis and compared to that seen in acute C. pneumoniae respiratory infection. By the micro-immunofluorescence test, five sarcoidosis patients had acute antibody, 15 had chronic antibody and four had no antibody against C. pneumoniae. By enzyme immunoassay, 20 sarcoidosis patients had antibody against ReLPS but that cross-reacts with chlamydial LPS. Immunoblot analysis of sera using purified C. pneumoniae elementary bodies showed that recognition of the 40 kDa C. pneumoniae major outer membrane protein was rare (20%). Reactivities with proteins with Mw of 42 K (70%), 60 K (65%), 98 K (55%) and 52 K (50%) were often noted. To study reactivity of chlamydial HSP 60 in sarcoidosis sera, sarkosyl-soluble (contains the 60 kDa HSP) and sarkosyl-insoluble (contains the 60 kDa structural protein) fractions of C. pneumoniae elementary bodies were prepared. The 60 kDa structural protein was recognized with equal frequency by sera from patients with sarcoidosis and acute respiratory infection, while the HSP 60 was more frequently recognized by sera with acute respiratory infection than sarcoidosis. Recombinant fusion proteins expressed from pGEX-2T containing overlapping DNA fragments of the C. pneumoniae 60 kDa HSP gene were purified. Different recognition patterns were identified for sera from sarcoidosis patients and from patients with acute C. pneumoniae respiratory infection.

Adult↗

Analysis of lymphocyte phenotype and cytokine activity in the inflammatory infiltrates of the upper genital tract of female macaques infected with Chlamydia trachomatis.

Chlamydia trachomatis infects the upper genital tract of millions of women, causing infertility and pelvic inflammatory disease, yet the inflammatory response to C. trachomatis infection is poorly understood. The cytokine response and the phenotype of infiltrating lymphocytes during C trachomatis infection of fimbria and ampulla autografts in subcutaneous pockets in Macaca nemestrina were characterized. About two-thirds of the infiltrating lymphocytes were CD8 T cells, with the remainder being CD4 T cells and B cells. Interleukin (IL)-2, IL-6, IL-10, interferon-gamma (IFN-gamma), and perforin mRNA were produced by the infiltrating cells, but IL-4 mRNA was absent. The presence of CD8 T cells and perforin mRNA suggest that activated cytolytic T cells are present. The presence of IL-2 and IFN-gamma mRNA and the absence of IL-4 mRNA suggest that Th1-type cytokines predominate during the acute phase of C. trachomatis infection of the upper genital tract.

Animals↗

In vitro activities of azithromycin, clarithromycin, and other antibiotics against Chlamydia pneumoniae.

The in vitro susceptibilities of Chlamydia pneumoniae isolates to macrolide, tetracycline, and quinolone antibiotics were determined. Tetracycline, clarithromycin, and erythromycin had the lowest MICs in the first cell culture passage. Azithromycin required the lowest concentration for complete inhibition of inclusion formation on the second pass into antibiotic-free medium, likely reflecting its high intracellular concentrations.

4-Quinolones↗

[The influence of job characteristics and workplace subculture on individuals' drinking behavior--an exploratory pilot study].

The purpose of this study was to explore how individuals' drinking behavior was associated with their jobs in terms of the amount consumed and its consequences. The researchers attempted to analyze the characteristics of job and workplace from structural, psychological, and cultural perspectives. The structural dimension referred to years serving in a company, years serving in a department, work position, work characteristics, and shift. The psychological dimension was addressed on perceived stress and work hazards. The cultural dimension of one's job consisted of formal and informal norms regarding one's drinking within the workplace. The result showed the occurrence of drinking-related problems was significantly associated with workplace subculture among the non-aboriginal Chinese males. However, none of the three perspectives as job characteristics was significantly associated with drinking amount. The findings imply that the workplace subculture plays a determinant role in affecting individual's drinking behavior, moreover, it could result in one's problem drinking.

Adolescent↗

Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery.

BACKGROUND: Chlamydia pneumoniae has been demonstrated in atherosclerotic lesions of coronary arteries and aorta. A seroepidemiological study found C pneumoniae-specific antibody more frequently in persons with significant carotid artery wall thickening than in matched control subjects. METHODS AND RESULTS: Fresh-frozen or formalin-fixed tissue obtained at carotid endarterectomy was examined by immunocytochemistry (ICC) and the polymerase chain reaction (PCR) for the presence of C pneumoniae. Five of five fresh-frozen and formalin-fixed carotid endarterectomy specimens were positive for C pneumoniae by ICC (three of five by PCR). A total of 56 archival formalin-fixed, paraffin-embedded carotid endarterectomy tissues from three hospitals were examined by ICC. Thirty-two were positive. Thirteen normal carotid artery tissue sections from six patients were negative for C pneumoniae. CONCLUSIONS: C pneumoniae organisms are frequently found in the advanced carotid atherosclerotic lesions of persons undergoing endarterectomy. Although these findings do not establish causality for C pneumoniae in carotid artery atherosclerosis, they should stimulate investigation of a possible causal or pathogenic role for the organism in the disease.

Aged↗

Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old).

An association of Chlamydia pneumoniae with atherosclerosis of coronary and carotid arteries and aorta has been found by seroepidemiology and by demonstration of the organism in atheromata. Age-matched control tissue from persons without atherosclerosis was usually not available. We studied autopsy tissue from young persons, many with no atherosclerosis, to determine whether C. pneumoniae is present in atheroma in young persons with early atherosclerosis and to compare the findings in age- and sex-matched persons without atherosclerosis. A left anterior descending coronary artery sample, formalin-fixed, from 49 subjects, 15-34 years of age, from the multicenter study called Pathobiological Determinants of Atherosclerosis in Youth (PDAY), was examined by immunocytochemistry and the polymerase chain reaction (PCR) for the presence of C. pneumoniae and by PCR for cytomegalovirus. A hematoxylin/eosin-stained section was used to determine disease present in the studied sample. Seven of the artery samples were found to have atheromatous plaque, 11 had intimal thickening, and 31 had no lesions. Eight of the samples were positive for C. pneumoniae by immunocytochemistry (n = 7) and/or PCR (n = 3). Six of the 7 (86%) atheroma, 2 of the 11 (18%) with intimal thickening, and none of the 31 normal-appearing coronary samples were positive. Four were positive by PCR for cytomegalovirus, 2 from diseased arteries and 2 from normal arteries. Examination of the adjacent left coronary artery sample with a fat stain found abnormalities in 25 of the patients, but 19 still showed no evidence of atherosclerosis as a result of either examination. Thus, C. pneumoniae is found in coronary lesions in young adults with atherosclerosis but is not found in normal-appearing coronary arteries of both persons with and without other evidence of atherosclerosis.

Adolescent↗

Postnatal development of cortical acetylcholinesterase-rich neurons in the rat brain: permanent and transient patterns.

The development of acetylcholinesterase (AChE) activity within cortical neurons of the rat brain was investigated using a histochemical method. The fate of these neurons in later stages of development was studied in animals in which AChE within cortical axons (mostly cholinergic) had been depleted by lesions of the cholinergic neurons of the basal forebrain or by injections of diisopropyl fluorophosphate. We designated neurons with medium to high intensity of reaction product as AChEH and neurons with a low intensity of reaction product as AChEL. Four groups of AChEH cortical neurons were detected: (1) AChEH Cajal-Retzius cells were present in layer I at birth (P0) and decreased steadily in number until none could be detected at P17 or thereafter. (2) AChEH neurons within layer VI and underlying white matter were present at P0, peaked in number and staining intensity at P8-P9, showed a moderate decrease in number at P11-P13 and a further decrease into adulthood. (3) AChEH polymorphic intracortical neurons appeared at P3-P4 in deep cortical layers and by P9 were present in layers II-VI. They continued to increase in number through P11-P14 at which time they displayed the adult pattern and were found in all cortical areas. (4) A large population of AChEH pyramidal neurons appeared at P1-P4, peaked at P8-P10 and was no longer visible at P21. In the adult cerebral cortex, few pyramidal neurons displayed AChE activity and these were almost always of the AChEL type. These results indicate that the AChE within cortical neurons is developmentally regulated and that the content of this enzyme helps to differentiate cortical neurons into distinct populations. The transient expression of AChE activity within cortical neurons suggests a role for this enzyme in the development of the cerebral cortex.

Acetylcholinesterase↗

Systemic dissemination of Chlamydia pneumoniae following intranasal inoculation in mice.

Although Chlamydia pneumoniae is a respiratory pathogen, there is increasing evidence of involvement of the organisms in anatomic sites other than the respiratory tract. A mouse model was used to study dissemination of organisms following intranasal, intravenous, and subcutaneous inoculation with C. pneumoniae. After inoculation by any of the three routes, the organism was isolated consistently from lungs and spleen. It was also detected in peritoneal macrophages after intranasal and intravenous inoculation. The ease with which the organism was disseminated in the mouse model raises the question of whether similar spread from the respiratory tract occurs in human C. pneumoniae infection.

Animals↗

Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.

Chlamydia pneumoniae TWAR has been associated with coronary heart disease by seroepidemiologic studies and direct detection of the organism in atheromatous lesions of coronary arteries and aorta. In this study, 38 fresh tissue specimens from patients with coronary artery lesions that were treated by directional coronary atherectomy were tested for C. pneumoniae. Twenty-three specimens were from patients with primary lesions and 15 were from patients with restenoses. C. pneumoniae was detected by polymerase chain reaction (PCR), immunocytochemical stain (ICC), or both in 20 of 38 specimens. Using cell identity markers, the organism was localized to macrophages. Ultrastructural evidence of the organism was found in the 2 specimens examined by transmission electron microscopy, which were also positive by both ICC and PCR. C. pneumoniae was found more frequently in tissues from restenoses than in primary lesions (P = .17). There was no relation between the frequency of detection of the organism and C. pneumoniae-specific antibody titers.

Adult↗

Reactivation of Chlamydia pneumoniae lung infection in mice by cortisone.

To study persistent infection, reactivation of Chlamydia pneumoniae lung infection in mice was attempted by immunosuppression with cortisone treatment. Four-week-old Swiss-Webster mice were treated with cortisone acetate (125 mg/kg) every other day for a total of six doses, starting on day 28 after intranasal inoculation of C. pneumoniae AR-39. C. pneumoniae was recovered from the lungs in 6 of 13 animals after six doses of cortisone, while control animals given saline remained negative. C. pneumoniae DNA was detected by polymerase chain reaction in the 6 culture-positive mice and 2 of 10 controls. The presence of pathogen DNA in this animal model suggested viable organisms in a culture-negative state.

Animals↗

The activity of azithromycin on the infectivity of Chlamydia trachomatis in human amniotic cells.

The effects of azithromycin on the infectivity and growth of Chlamydia trachomatis were investigated in primary human amniotic epithelial cells. Infection was prevented when cultures were exposed to the drug 6 h after inoculation and growth was completely inhibited when the drug was added to cultures 24, 48, 72 h or 7 days after infection. The same inhibition was observed at 0.5, 1.0 and 5.0 mg/L. Ultrastructural observations depicted interruption in the growth cycle of the chlamydia and ghost-like envelopes were present in the near empty inclusions. Azithromycin is effective in inhibiting chlamydial growth no matter when treatment is initiated after infection.

Amnion↗