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Biomedical subjects

R B Jones

Publications and source records attributed to R B Jones.

At least 235 records · Page 13Linked to original sources

Differences among mononuclear cell subpopulations in HIV seropositive or seronegative homosexual and heterosexual men as determined by four-color flow cytometry.

Four-color cell surface immunofluorescence and flow cytometry analysis was used to quantitate mononuclear cell subpopulations from HIV seropositive (HIV+) and seronegative (HIV-) homosexual men and heterosexual men. HIV+ men were divided into two groups based on peripheral blood CD4/mm3 of greater than 500 or less than 500. CD4+ cells that were simultaneously CD45R-, CDw29-, and 13- were significantly less in HIV+ men with less than 500 CD4/mm3 (17%) compared to heterosexual men (34%). This lower percentage of "CD4 only" cells in HIV+ males with less than 500 CD4/mm3 correlated with a significantly higher percentage of CD4+ cells that were CD45R+, CDw29+, and 13+ in these individuals. CD8+ cells that were CD45R+, 13+, but CD38-, were significantly less in HIV+ men with less than 500 CD4 as compared to HIV- homosexual men. In contrast, a second CD8+ subpopulation that was CD45R-, CD38+, and either 13+ or 13- was significantly greater in less than 500 HIV+ men as compared to both HIV- homosexual men and heterosexual men. A significant difference in this subpopulation was observed between the less than 500 and greater than 500 HIV+ groups and correlated with seropositivity for viral p24 antigen. Interestingly, CD8+ cells that were CD45R+, as well as CD38+, and either 13+ or 13- were significantly greater in the less than 500 HIV+ group compared to the greater than 500 HIV+ group, and did not correlate with p24 seropositivity. The percentage of monocyte/macrophages that were CD4- or expressed dim CD4 immunofluorescence, but were 13+, was significantly greater in HIV+ men (43%) compared to HIV- homosexual men (27%). In summary, we have identified previously undescribed mononuclear cell subpopulations that were altered with HIV infection and, in some cases, correlated with the stage of disease.

ADP-ribosyl Cyclase↗

Efficacy and safety of ofloxacin in the treatment of nongonococcal sexually transmitted disease.

This study compared doxycycline with ofloxacin in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women and compared both drugs in the treatment of infections due to Chlamydia trachomatis in both men and women. Informed consent was obtained from all subjects. Eighteen men with nongonococcal urethritis and 12 with previously positive chlamydial cultures were randomly treated with doxycycline or ofloxacin. Eleven women with mucopurulent cervicitis, 14 with a previous positive untreated chlamydial culture, and nine having sexual contacts with men known to have chlamydial urethritis also were randomly treated. Culture specimens for chlamydia were obtained before treatment, five to nine days after therapy (return visit 1), and 21 to 28 days after therapy (return visit 2). Cultures for Ureaplasma urealyticum were obtained only in men. There were no significant differences in results in patients treated with doxycycline or ofloxacin. All but three of 20 men with symptoms were symptom-free on return visit 1 and all were symptom-free on return visit 2. Thirteen women with mucopurulent cervicitis had all resolved at visit 1, although signs of cervicitis reappeared at the second visit in two patients treated with doxycycline and one treated with ofloxacin. All patients with positive chlamydial cultures had negative cultures at the first return visit. One patient treated with doxycycline was positive at the second return visit. Laboratory and clinical abnormalities were mild and did not prevent completion of therapy. These data, together with previous published and unpublished data, indicate that ofloxacin is as effective as doxycycline in the treatment of chlamydial infections. The study also demonstrated that ofloxacin and doxycycline were equally effective in the treatment of nongonococcal urethritis in men and mucopurulent cervicitis in women.

Chlamydia Infections↗

High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study.

A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was cardiac toxicity. Objective tumor regression occurred in 14 of 18 evaluable cases, with a median duration of 3.5 months. Pharmacokinetic evaluation of melphalan in 20 patients revealed a dose-related increase in maximum plasma concentration (Cmax) and area under the curve (AUC). Perturbation of the melphalan plasma half-life and AUC, associated with severe toxicity, resulted when renal insufficiency occurred. The results suggest that high-dose combination cyclophosphamide, cisplatin, and melphalan produces frequent, rapid responses in breast cancer, melanoma, and sarcoma, although with significant extramedullary toxicity. The pharmacokinetics suggest that modification of the treatment schedule may result in a reduction of treatment-related toxicity.

Adult↗

Chronic stressors, tonic immobility and leucocytic responses in the domestic fowl.

Tonic immobility (TI) fear reactions and heterophil/lymphocyte (H/L) ratios were measured in individually caged Brown Leghorn pullets before and after their exposure to one of three procedures lasting approximately 72 hr. These were: ad lib feeding (controls), fasting (removal of food) or frustration of feeding (fasting plus denial of access to visible food). H/L ratios were elevated after fasting or frustration, illustrating the stressful nature of these procedures, but remained unaltered in the controls. Pretreatment TI responses were similar in all groups. Susceptibility and response duration were reduced upon retesting presumably through habituation, but this effect was relatively homogeneous across groups. Any direct effect of fasting/frustration upon fearfulness seemed unlikely because the mean TI responses of control and stressed birds were similar. However, whereas a rank order based on TI durations was repeatable upon retesting in the controls, it was destabilised in the stressed groups. Positive intraindividual correlations were found between pretreatment TI durations and subsequent H/L responses to fasting/frustration. This suggests that leucocytic responses to chronic stressors may be greater in fearful pullets than in less fearful birds.

Animals↗

Physiological changes during tonic immobility in Gallus gallus var domesticus.

Physiological parameters were examined in the hen in response to the induction of tonic immobility (TI). The induction of TI was associated with EEG arousal, low shank temperature and elevated heart rate. However, shortly after the adoption of TI, the EEG showed a predominantly slow-wave deactivated pattern, muscle tone fell and sympathetic nervous activity was reduced, as indicated by declining heart rate and peripheral vasodilation. Core temperature remained constant at 42 degrees C throughout the immobility response. Several instances of EEG-behavioural dissociation were observed. The results are discussed in terms of "cut-off" and waning of the induced fear state.

Animals↗

In vitro accumulation of thyroid hormones by cultured rat hepatocytes and the biliary excretion of iodothyronines in rats treated with a novel histamine H2-receptor antagonist.

The administration of SK&F 93479, a novel histamine H2 antagonist, to Wistar rats has been shown to produce thyroid lesions associated with an increased clearance of plasma thyroxine (T4) and elevated plasma TSH concentrations. To determine if these changes were mediated via an increase in the hepatic clearance of thyroid hormones, the biliary clearance and hepatic accumulation of iodothyronines were measured in rats and cultured hepatocytes treated with SK&F 93479. Both the in vitro and in vivo results showed that treatment with SK&F 93479 caused an increased hepatic accumulation (approx. 200% of control) and biliary excretion (2-3-fold control values) of T4 but had little or no effect on T3 uptake. The in vitro studies showed that the treatment related increase in hepatic thyroxine accumulation was temperature and therefore probably energy dependent, while inhibition of cytochrome P-450 dependent enzyme activity did not alter the accumulation of T4 suggesting that the parent compound and not some oxidative metabolite was responsible for the hepatic effects. Chromatographic analysis of bile from SK&F 93479 and phenobarbitone-treated rats showed that in the latter animals 81% of the T4 was present as the glucuronide conjugate (consistent with enzyme induction) whereas in the SK&F 93479-treated rats only 25% was present as the conjugate with 75% being in the unconjugated form. These studies show that SK&F 93479 increases the hepatic accumulation and biliary clearance of T4 by a novel mechanism not associated with liver microsomal enzyme induction.

Animals↗

Recovery of Chlamydia trachomatis from endometrial and fallopian tube biopsies in women with infertility of tubal origin.

In order to examine the role of chronic active chlamydial infection in tubal infertility, cultures for Chlamydia trachomatis were performed on endometrial biopsies from 38, and fallopian tube biopsies from all, of 52 women undergoing tubal surgery for infertility. C. trachomatis was recovered from one or both sites in 8 of 52 (15%). Five of 6 women with positive fallopian tube cultures had endometrial cultures performed, and of these, 4 (80%) were positive. Three culture-positive women had been treated with tetracycline or doxycycline. Multiple blind passage in tissue culture was required for recovery of all six fallopian tube and four of the six endometrial isolates. No specific anatomic lesion was associated with documented infection. Chronic active chlamydial infection is frequently associated with tubal infertility, may persist despite therapy, and often can be detected by endometrial biopsy culture.

Adolescent↗

Adrenocortical and heterophil/lymphocyte responses to challenge in hens showing short or long tonic immobility reactions.

1. Adult White Leghorn hens showing short or long tonic immobility reactions were classified as low-fear (LF) or high-fear (HF) responders, respectively. Following cannulation, their adrenocortical responsiveness to ACTH administration and the effects of chronic frustration induced by thwarting of feeding on plasma corticosterone concentrations and heterophil/lymphocyte (H/L) ratios were measured at regular intervals. 2. ACTH injection elicited significant and similar mean increases in circulating corticosterone concentrations in both the LF and HF groups. 3. Absolute H/L ratios were higher in HF than in LF hens after cannulation, although both groups showed similar proportional increases from pre-operation ratios. 4. Plasma corticosterone concentrations and H/L ratios were significantly increased at 20 h and 44 h respectively after the frustration of feeding regime began. Thus, adrenocortical activation preceded increases in H/L ratios but, whereas the elevated plasma corticosterone concentrations found after 20 h remained virtually constant thereafter, H/L ratios rose progressively throughout the 68 h frustration period. 5. There were no significant differences between groups in their plasma corticosterone and H/L responses to frustration. However, a consistent trend towards greater adrenocortical activation was observed in the HF than in the LF hens.

Adrenal Cortex↗

Association of recurrent chlamydial infection with gonorrhea.

To determine whether concurrent gonorrhea reactivates latent chlamydial infection, we studied 74 recurrent chlamydial infections and the effect of concurrent gonorrhea at the recurrent episode on the chlamydial serovar identified. Serotyping of 74 recurrent pairs of chlamydial isolates from patients attending a sexually transmitted diseases clinic indicated that 47.1% (16 of 34) with gonorrhea at the time of recurrence harbored chlamydiae of the same serovar as at the initial infection, while only 22.5% (9 of 40) without gonorrhea had the same serovar (P = .03). The proportion of recurrences by the same serovar in the group without gonorrhea did not differ from the proportion predicted by a random exposure model (22.2% vs. 18.4%, P = .46), while the proportion in the gonorrhea group did (47.1% vs. 19.8%, P less than .0001). The possibility of reinfection did not appear more likely in the group with gonorrhea than in the group without. These observations support the hypothesis that concurrent gonorrhea can reactivate latent chlamydial infection.

Adult↗

Correlation of infecting serovar and local inflammation in genital chlamydial infections.

The relationship between acute inflammation and serovar of Chlamydia trachomatis was evaluated in patients with genital chlamydial infection who attended a sexually transmitted diseases clinic. Polymorphonuclear leukocytes (PMNLS) were enumerated on Gram's-stained smears of endourethral contents in men; cervicitis was scored by visual observation of the endocervix in women. Isolates were serotyped with a monoclonal antibody-based radioimmunoassay. The distribution of serovars in 99 women did not differ in the presence or absence of cervicitis or concurrent gonorrhea. An overall difference (P = .037) was observed when serovar distributions in men with less than or equal to 3 PMNLs (n = 42), greater than or equal to 10 PMNLs (n = 41), and gonococcal urethritis (n = 42) were compared. Follow-up pairwise comparisons revealed that men with less than or equal to 3 PMNLs had fewer isolates of serovars F and G than did men with greater than or equal to 10 PMNLs (P less than .05). No strong overall association was observed between inflammation and serovar.

Chlamydia Infections↗

Detection of surface-exposed epitopes on Chlamydia trachomatis by immune electron microscopy.

The cell surfaces of two Chlamydia trachomatis serovars were explored by immune electron microscopy with monoclonal antibodies that recognize a number of chlamydial outer-membrane components. Species, subspecies and serovar-reactive epitopes on the major outer-membrane protein (MOMP) of a lymphogranuloma venereum biovar strain, L2/434/Bu, and a trachoma biovar strain, F/UW-6/Cx, were exposed on the surfaces of both elementary bodies (EBs) and reticulate bodies (RBs). Three epitopes on MOMP were inaccessible on EBs and RBs of both strains. These included a genus-reactive, species-reactive, and a subspecies-reactive epitope. In contrast, genus-specific epitopes on lipopolysaccharide (LPS) were not detected on the EB surface, but were clearly expressed on RBs of both L2/434/Bu and F/UW-6/Cx chlamydiae. Antibodies specific for the 60 kDa and 12 kDa 'cysteine-rich' outer-membrane proteins did not react with surface epitopes on either EBs or RBs. These data provide evidence that MOMP is a major surface antigen of both morphological forms, whereas some portions of the LPS molecule are exposed on the RB surface but become inaccessible to antibody after conversion to the infectious EB form.

Antibodies, Monoclonal↗

How effective is the referral chain for diabetic retinopathy?

Despite the availability of effective photocoagulation treatment, diabetic retinopathy remains the main cause of blindness in persons aged between 20 and 64 years. We have examined the effectiveness of the referral chain for retinopathy by auditing medical records for a representative sample being 226 diabetic patients (35% of attenders) referred to a special photocoagulation clinic. Patients were classified as 'late' or 'not late' by using an algorithm which accounted for the state of retinopathy at referral and the previous frequency of eye examination. Forty-four patients (19%) were considered to have been referred late. These were mainly younger onset patients, aged between 30 and 40, and not attending a diabetic clinic. Patients not attending any other outpatient clinic were 27 times more likely to be referred late.

Adult↗

Response to growth hormone-releasing hormone as evidence of hypothalamic defect in optic nerve hypoplasia.

Hypothalamic-pituitary function was studied in four children with Optic Nerve Hypoplasia (ONH). All were found to be growth hormone deficient when provoked with glucagon or insulin induced hypoglycaemia (ITT), but did respond to bolus injection of GHRH. This indicates a primary hypothalamic defect. Virtual absence of pituitary tissue on high resolution CT scan explained the poor response of one child. One child has shown an excellent response to treatment with subcutaneous GHRH, which is physiologically the most appropriate treatment for this condition.

Child↗