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K Edmonds

Publications and source records attributed to K Edmonds.

At least 19 recordsLinked to original sources
PubMed1997

Eye and gonad: role in the dual-oscillator circadian system of female Japanese quail.

Experiments were conducted to determine the anatomic and physiological basis of the dual-oscillator circadian system of female Japanese quail. After blocking of ocular light perception by eye-patching, the circadian body temperature rhythm dissociates into two circadian components in continuous lighting (LL). One component free runs with a period significantly shorter than 24 h [mean period (tau) = 22.7 h] and is driven by an ocular pacemaker, whereas the other component free runs with a period significantly longer than 24 h (tau = 26.3 h). The long free-running rhythm is driven by the same circadian clock that drives the circadian rhythm of ovulation. The expression of the long free-running rhythm in LL depends on the presence of the ovary: body temperature rhythmicity is abolished by ovariectomy. The two free-running oscillators in eye-patched birds showed evidence of mutual interaction. Significantly, the phase relationships that occur as the two oscillators interact can determine whether or not ovulation occurs. The results are discussed in terms of an "internal coincidence" mechanism for photoperiodic time measurement.

Animals↗
PubMed1996

Generalized immune activation in pulmonary tuberculosis: co-activation with HIV infection.

Parameters of immune activation/differentiation were studied in a group of newly diagnosed HIV- and HIV+ pulmonary tuberculosis (TB) patients. Compared with controls, HLA-DR expression on both CD4 and CD8 T cells from the HIV- TB patients was approximately doubled; HLA-DR on T cells from the HIV+ group was tripled. The monocytes from both groups of patients expressed abnormally high levels of the Fc gamma receptors I and III. Serum levels of tumour necrosis factor-alpha (TNF-alpha), neopterin and beta 2-microglobulin were increased in HIV- and even more so in HIV+ TB patients. The expression of HLA-DR on T cell subsets and of Fc gamma R on monocytes correlated with each other, but not with serum activation markers. This pattern of non-specific activation during TB infection may be associated with enhanced susceptibility to HIV infection.

Adult↗
PubMed1996

Anti-endometrial antibodies in women measured by an enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure anti-endometrial antibody concentrations in the serum of women with endometriosis. Pooled cytosolic protein extracts from the endometrial gland cells of 10 women were used as an antigen source. Serum samples were obtained from women with endometriosis before (n = 51) and after 6 months treatment with danazol or nafarelin (n = 30). Control sera came from women with a normal pelvis at laparoscopy, performed for sterilization (n = 23) or the investigation of pain and/or infertility (n = 22), 13 women with Rokitansky syndrome, and 10 umbilical cord bloods and adult males. There were no significant differences in serum anti-endometrial antibody concentrations before and after treatment, or between women with endometriosis and without endometriosis. Concentrations were lower in male and cord blood serum than in female's serum (P < 0.0001). We conclude that the ELISA is not a useful diagnostic tool for endometriosis unless more specific antigens can be isolated.

Adult↗
PubMed1995

The circadian rhythm of thermoregulation in Japanese quail. II. Multioscillator control.

Most biochemical, physiological, and behavioral processes in vertebrates show significant daily rhythms. Under constant conditions, these rhythms exhibit an endogenous periodicity around 24 h showing that they are driven by an internal circadian clock. In Japanese quail, the circadian clock driving activity and body temperature rhythms is functionally organized as a dual-oscillator system. Under certain conditions, such as switching birds from light:dark (LD) 12:12 to continuous darkness (DD), the body temperature rhythm splits into two circadian components that free-run independently before recoupling in a normal phase-relationship. The behavior of the activity rhythm parallels that of the body temperature rhythm, supporting the hypothesis that both rhythms are driven by the same set of oscillators. In some instances, recoupling fails to occur and birds continue to exhibit two circadian components that free-run independently. Dual-oscillator control of body temperature was observed in normal birds, pinealectomized birds, and optic nerve sectioned birds. However, birds were rendered arrhythmic by complete eye removal. It is proposed that the central circadian system (suprachiasmatic nuclei?) acts as a complex pacemaker that is functionally organized as two sets of oscillators and that circadian input from the eyes is necessary to preserve the integrity of this complex pacemaker.

Animals↗
PubMed1995

The circadian rhythm of thermoregulation in Japanese quail: III. Effects of melatonin administration.

Recent studies indicate that the circadian pacemakers in the eyes of Japanese quail are coupled to the rest of the circadian system by both neural and hormonal outputs. The effects of exogenous melatonin administration on circadian body temperature and activity rhythms of quail were tested to determine whether melatonin could be the hormonal link involved. Continuous melatonin administration caused arrhythmicity or period changes in the body temperature and activity rhythms of pinealectomized and sham-pinealectomized birds held in constant darkness and also significantly decreased the amplitude of the body temperature rhythms of normal birds held on light:dark 12:12. Further, melatonin entrained the body temperature and activity rhythms of normal birds when administered daily via the drinking water. The results show that melatonin can affect the circadian system of quail and support the hypothesis that melatonin is importantly involved in linking pacemakers in the eyes to the rest of the circadian system.

Animals↗
PubMed1994

An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin.

Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination with cimetidine can produce objective antitumor responses in some patients with advanced renal cell carcinoma. The purpose of this report is to review the clinical development of coumarin, with or without cimetidine, with special reference to renal cell carcinoma (RCC). Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented. The rationale and study design of an active randomized, double-blinded, placebo-controlled trial of coumarin for RCC are discussed. A progress report is given for an ongoing phase I trial of oral 7-hydroxycoumarin, the major human metabolite of coumarin.

Adult↗
PubMed1993

Anti-Mycobacterium avium activity of quinolones: in vitro activities.

The MICs of 88 quinolones against 14 selected reference and clinical strains of Mycobacterium avium-M. intracellular complex were determined. Agents tested included ciprofloxacin, sparfloxacin (PD 131501), and 86 other experimental quinolones. Test strains were selected to represent various susceptibilities to ciprofloxacin and other drug resistance profiles. MICs were determined by the microdilution method in 7HSF broth, with incubation for 14 days at 35 degrees C. The results showed 25 of the quinolones to be active against the strains, with MICs for 90% of the strains (MIC90s) of 2 to 32 micrograms/ml. Ten of these compounds had activities equivalent to or greater than that of ciprofloxacin. The most active compound was PD 125354, with an MIC50 of 0.5 micrograms/ml and an MIC90 of 2 micrograms/ml; comparable values for ciprofloxacin were 4 and 8 micrograms/ml, respectively. The next most active compounds, with MIC90s of 4 micrograms/ml, were sparfloxacin (PD 131501), PD 123982, PD 135144, and PD 119421. MIC90s of PD 131575, PD 126889, PD 122642, PD 139586, and PD 143289 were 8 micrograms/ml. Further evaluation of the most active agents is warranted, as is assessment of structure-activity relationships of active and inactive agents to elucidate the active portions of the compounds and to lead to the development of compounds with enhanced activity.

Anti-Infective Agents↗
PubMed1992

Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus.

The metabolism and mode of action of penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] were studied and compared with those of acyclovir. In uninfected MRC-5 cells, low concentrations of the triphosphates of penciclovir and acyclovir were occasionally just detectable, the limit of detection being about 1 pmol/10(6) cells. In contrast, in cells infected with either herpes simplex virus type 2 (HSV-2) or varicella-zoster virus (VZV), penciclovir was phosphorylated quickly to give high concentrations of the triphosphate ester. Following the removal of penciclovir from the culture medium, penciclovir-triphosphate remained trapped within the cells for a long time (half-lives, 20 and 7 h in HSV-2- and VZV-infected cells, respectively). In HSV-2-infected cells, acyclovir was phosphorylated to a lesser extent and the half-life of the triphosphate ester was only 1 h. We were unable to detect any phosphates of acyclovir in VZV-infected cells. (S)-Penciclovir-triphosphate inhibited HSV-1 and HSV-2 DNA polymerase competitively with dGTP, the Ki values being 8.5 and 5.8 microM, respectively, whereas for acyclovir-triphosphate, the Ki value was 0.07 microM for the two enzymes. Both compounds had relatively low levels of activity against the cellular DNA polymerase alpha, with Ki values of 175 and 3.8 microM, respectively. (S)-Penciclovir-triphosphate did inhibit DNA synthesis by HSV-2 DNA polymerase with a defined template-primer, although it was not an obligate chain terminator like acyclovir-triphosphate. These results provide a biochemical rationale for the highly selective and effective inhibition of HSV-2 and VZV DNA synthesis by penciclovir and for the greater activity of penciclovir than that of acyclovir when HSV-2-infected cells were treated for a short time.

Acyclovir↗
PubMed1989

Polycystic ovary syndrome in a virilised, premenarcheal girl.

A premenarcheal girl aged 12 years presented with an abdominopelvic mass and virilisation. A large ovarian cyst was removed at laparotomy. A histological diagnosis of polycystic ovarian syndrome was made, with no evidence of an associated masculinising tumour.

Child↗
PubMed1988

Cell-mediated immune responses in human infection with Onchocerca volvulus.

Mechanisms involved in modulation of the immune response in persons with chronic Onchocerca volvulus infection are poorly understood. In this study in vitro reactivity of PBMC to O. volvulus antigen (Ovag), streptolysin O (SL-O) and the mitogen PHA was tested in 62 infected individuals (INF), 17 persons living in the endemic area with exposure to the infection, but with no detectable infection (END), and 7 healthy controls (CTRL) in Liberia, West Africa. Mean blastogenic responses to Ovag were minimal and did not differ between the groups. There was, however, heterogenous reactivity to Ovag in the INF and END. For example, individuals with a history of therapy, and half of those less than 17 yr old who were tested, showed high responses. No significant differences in the response to SL-O or PHA were detected between the groups. IL-2 production in response to Ovag was minimal in the majority of infected subjects. Exogenous IL-2 was found to cause a significant increase in mean responses to Ovag and SL-O in INF and END only. Similarly, Ovag did not stimulate IL-1 production in most INF, whereas stimulation with LPS led to significantly greater production of IL-1. Depletion of plastic and nylon wool adherent cells did not increase responses to parasite-related antigen in INF, END or CTRL; however, responses to SL-O were augmented in INF, an effect that was also observed in CTRL. Finally, depletion of CD8 or CD16 cells in INF by C lysis did not increase blastogenic responses. These results indicate that cell-mediated immunity to parasite-related Ag as reflected in lymphocyte responses in vitro is diminished in infected individuals, and that this may be caused by defects in T cell activation.

Animals↗
PubMed1987

Augmentation of skin test reactivity and lymphocyte blastogenesis in patients with AIDS treated with transfer factor.

Nine patients with the acquired immunodeficiency syndrome (AIDS) were administered four doses of pooled transfer factor obtained from the lymphocytes of three healthy controls and three homosexuals with stable lymphadenopathy and serum antibody to the human immunodeficiency virus. Before receiving transfer factor, all patients exhibited anergy to skin test antigens. After four weeks of transfer factor therapy, six of seven patients tested had at least one skin test response. Lymphocyte blastogenic responses to phytohemagglutinin rose from a stimulation index of 6.77 +/- 1.31 before treatment to 19.77 +/- 6.24 after four weeks of transfer factor therapy. Smaller but significant increases were also seen in blastogenic responses to antigens. Improvements in immune responses diminished after administration of transfer factor was halted. Thus, administration of transfer factor to patients with AIDS resulted in partial immune reconstitution. Further studies are indicated to examine the clinical efficacy of this immune response modifier in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Spontaneous production of a suppressor factor by a human macrophage-like cell line U937. II. Suppression of antigen- and mitogen-induced blastogenesis, IL 2 production and IL 2 receptor expression in T lymphocytes.

U937, a human macrophage-like cell line, spontaneously produces a factor which inhibited blastogenic responses of human blood T lymphocytes stimulated with tuberculin-purified protein derivative (PPD) or phytohemagglutinin (PHA). We investigated the mechanism of suppressor action of the U937 factor. The U937 suppressor factor inhibited interleukin 2 (IL 2) production by human blood T lymphocytes stimulated with PPD or PHA. IL 1 did not overcome the inhibitory action of the U937 factor on PPD-induced IL 2 production by human blood T lymphocytes. The U937 factor also inhibited the production of IL 2 by a human leukemic cell line, JURKAT, stimulated with PHA. The U937 suppressor factor interfered with the expression of Tac antigen (IL 2 receptor) on PPD- or PHA-stimulated blood T lymphocytes. The inhibitory activity of the U937 factor on Tac expression was not affected by the addition of IL 2 or a crude lymphokine-containing T cell supernatant. Tac expression was more sensitive than IL 2 production to inhibition by U937-conditioned medium. The U937 suppressor factor was precipitable by 33 to 67% saturated ammonium sulfate and was inactivated at pH 2 or pH 11. Sephacryl S-200 Gel filtration analysis of U937 culture supernatants revealed that the inhibitory activities for blastogenesis, IL 2 production, and Tac expression co-purified in fractions with an apparent m.w. between 67,000 and 130,000. These data indicate that U937 spontaneously produces a macromolecular suppressive factor with major locus of action on the production of IL 2 and the expression of the IL 2 receptor.

Cell Line↗
PubMed1981

Spontaneous cytotoxicity of human peripheral blood mononuclear cells for the lymphoblastoid cell line CCRF-CEM: augmentation by bacterial lipopolysaccharide.

Spontaneous cell-mediated cytotoxicity (SCMC) of human peripheral blood mononuclear cells for a poor target, CCRF-CEM, a lymphoblastoid cell line, was rapidly and markedly elevated by E. coli lipopolysaccharide (LPS). SCMC for K562, a myeloid cell line sensitive to SCMC, was only slightly elevated by LPS. The cytotoxicities of both adherent and non-adherent mononuclear cells for CCRF-CEM were elevated. A response to LPS was found in Fc gamma R-positive and Fc gamma R-negative T cells. LPS increased the binding of non-adherent cells to both targets, but analysis of the binding suggests that a subsequent step, either triggering of the cytotoxic mechanisms or susceptibility of the target was the basis for the increased SCMC.

Adult↗