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Biomedical subjects

A Payne

Publications and source records attributed to A Payne.

At least 37 records · Page 2Linked to original sources

A new family of Greek origin maps to the CRD locus for autosomal dominant cone-rod dystrophy on 19q.

Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of genetic disorders of the retina, representing the most frequently inherited form of visual handicap, affecting approximately 1.5 million people world wide. To date, more than 40 genetic loci have been implicated in RD. One of them, the CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to chromosome 19q and has previously been reported in a single large family of British origin. We now report a new family with severe early onset CRD, phenotypically very similar to the British family, which also maps to 19q, but is of Greek origin. Haplotype data of the Greek family showed no recombination between and including markers D19S219 and D19S246 and linkage analysis gave a lod score of 2.7 (at theta=0) with marker D19S412, confirming the data obtained in the British family.

Chromosome Mapping↗

Selective phosphodiesterase inhibitors modulate the activity of alveolar macrophages from sensitized guinea-pigs.

The aim of this study was to investigate the effects of selective phosphodiesterase (PDE)3 and PDE4 inhibitors on arachidonate release by alveolar macrophages from sensitized and challenged guinea-pigs. Guinea-pigs were sensitized and challenged with ovalbumin administered by aerosol. Bronchoalveolar lavage was performed 48 h later and the PDE and cyclic adenosine monophosphate (cAMP) contents of or the arachidonate release from alveolar macrophages, stimulated in vitro with N-formyl-Met-Leu-Phe (fMLP), were evaluated. PDE3 and PDE4 activities were detected in preparations of macrophage lysate from sensitized challenged and sensitized control animals. Oral pretreatment, prior to antigen challenge in sensitized guinea-pigs, with rolipram or Ro 20-1724 (PDE4 inhibitors) but not milrinone (PDE3 inhibitor) significantly reduced the arachidonate release from alveolar macrophages. In vitro incubation of alveolar macrophages from challenged guinea-pigs with Ro 20-1724 or the cAMP analogue dibutyryl cAMP (db-cAMP) but not milrinone or the cyclic guanosine monophosphate (cGMP) analogue 8-bromo-cGMP (8-br-cGMP) significantly reduced arachidonate release. Incubation of the cells with a combination of milrinone plus rolipram or Ro 20-1724 elicited a marked and significant reduction in arachidonate release by alveolar macrophages stimulated with fMLP. In conclusion, these data show that phosphodiesterase-4 isoenzyme may regulate the release of inflammatory mediators such as arachidonate from macrophages through an increase in intracellular cyclic adenosine monophosphate. This suggests that phosphodiesterase-4 inhibitors have potential in the treatment of inflammatory disorders of the lung.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Antisense targeting of delta opioid receptors in NG 108-15 cells: direct correlation between oligodeoxynucleotide uptake and receptor density.

Antisense oligodeoxynucleotides (ODN) have been used to inhibit the function of a number of structurally defined neurotransmitter receptors in vivo by transiently disrupting their expression in the CNS. However, issues concerning the cellular and molecular mechanisms of these ODN often raise questions about the specificity of such ODN-mediated "knock-down" of target proteins. This study sought to extend our in vivo "knock-down" of the delta opioid receptor (DOR) by targeting this receptor in the NG 108-15 cells with an antisense ODN for the DOR and by using a polyclonal antibody raised against this receptor to determine the efficiency and selectivity of the antisense ODN in inhibiting expression of the DOR. By fluorescence tagging the ODN and immunofluorescence labeling the DOR, we monitored the uptake efficiency of the ODN and the DOR density in individual cells that had been treated with the antisense ODN or with a mismatch control. Quantitative fluorescence image analysis showed that the uptake of ODN by NG 108-15 cells was time- and concentration-dependent and that it was not uniform within a population. Treatment with the antisense ODN elicited an inverse correlation between DOR immunoreactivity and the ODN fluorescence in individual cells. No correlation was found in cells treated with the mismatch control. These findings suggest that the antisense ODN-mediated "knock-down" of the DOR is governed by the sequence specificity of the ODN and the efficiency of its uptake by the target cells in a time- and concentration-dependent manner. These data provide further evidence in support of the selectivity of antisense ODN targeting and the utility of these molecules as an effective tool in neuropharmacological studies.

Animals↗

Rhesus immunization after renal transplantation.

Previous reports, before the advent of cyclosporine, suggest that the small amount of blood transplanted with a kidney can result in rhesus D (RhD) antibody production. We looked for retrospective and current evidence of primary RhD antibody production following renal transplantation in RhD-negative recipients of an RhD-positive kidney. Of 42 patients, all on triple immunosuppressive therapy, 2 (5%) were found to have an RhD antibody identified for the first time after transplantation. As the number of pregnancies in transplant recipients increases, the small risk of primary immunization and subsequent risk of hemolytic disease of the newborn will become more important. Therefore, we recommend that all RhD-negative women of child-bearing age receiving an RhD-positive solid organ transplant are given a prophylactic dose of 500 IU of anti-D immunoglobulin intramuscularly at the time of transplantation.

Antibodies↗

Controlled evaluation of thermal biofeedback in treatment of elevated blood pressure in unmedicated mild hypertension.

In the first of two studies, 42 unmedicated mild hypertensives completed either 16 sessions of thermal biofeedback (TBF) training for hand (7 sessions) and foot (9 sessions) warming or 8 weeks of monitoring BPs at home. There was a trend (p < .10) for more of those treated (57.1%) to have DBPs lower than 90 mm Hg than for those only monitoring BPs at home (33%). Analyses of clinic BP values from random zero sphygmomanometer measurements, from 24-hour ambulatory BP monitoring, and from home BP measurements made by the patient showed no advantage for treatment versus BP monitoring. Sixteen of the 21 patients in BP monitoring were later treated. Analyses of treatment effects across all treated subjects by gender revealed a significant (p = .02) decrease in DBP for treated female subjects (n = 13) but not for males (n = 24). In the second study the 22 initial treatment successes, that is, those whose DBP was below 90 mm Hg at posttreatment (59.4% of those who completed treatment), were randomized to an intensive follow-up (monthly visits for 6 months, then visits every two months) emphasizing regular home practice with an electronic TBF device or regular follow-up (visits every 3 months). Twelve of the 22 were still normotensive at 12 months. There were no differences at any point during the follow-up between the two conditions in success rate or BPs despite a numerical advantage in reported frequency of home practice by those in the intensive follow-up condition.

Adult↗

Differential effects of fedotozine compared to other kappa agonists on diuresis in rats.

The aim of our study was to test the effect of fedotozine (0.1-30 mg/kg, s.c.), a novel kappa opioid agonist, on water diuresis in the conscious hydrated rat. Its effect was compared to that of morphine (2.5-10 mg/kg), a mu opioid agonist and to some of the recognized kappa agonists described in the literature: bremazocine (0.3-30 micrograms/kg), tifluadom (0.1-3 mg/kg), Cl 977 1-1000 micrograms/kg), (-)-cyclazocine (0.01-1 mg/kg), PD 117,302 (0.03-3 mg/kg), U-50,488h (0.25-10 mg/kg) and U-69,593 (0.3-3 mg/kg). The effect of fedotozine was also tested after intracerebroventricular administration (100 micrograms/kg) and compared to that of U-50,488h (10-30 micrograms) and dynorphins A(1-17), A(1-13) and B(1-13) (2.5-10 micrograms). All the reference kappa agonists administered by the s.c. route induced water diuresis, whereas morphine inhibited diuresis and electrolyte excretion. However, fedotozine (0.1-30 mg/kg s.c.) had no effect on diuresis, even after low doses of naloxone (0.1 mg/kg s.c.) or nor-BNI (10 mg/kg s.c.), and at 1 mg/kg had inconsistent effects on electrolyte elimination. When administered in the lateral ventricle of the brain, U-50,488h and dynorphin A(1-17) induced water diuresis, unlike fedotozine (100 micrograms), DYN A(1-13) and DYN B(1-13) that had no effect on urine output. Furthermore, fedotozine did not alter the diuretic effects of U-50,488h. These results suggest that fedotozine is an atypical kappa agonist, lacking activity on the kappa receptor subtypes regulating diuresis.

Animals↗

Free alpha-subunits of human chorionic gonadotropin in preeclampsia.

OBJECTIVE: To investigate free alpha-human chorionic gonadotropin (hCG) as a marker of preeclampsia. METHODS: Four groups of patients were studied: normal pregnancies, preeclampsia, eclampsia and normal pregnant women <20 weeks' gestation. Patients were further divided according to parity and gestational age (< or =20, 21-30, 31-40 weeks). An immunoradiometric assay employing monoclonal antibodies specific for free alpha-hCG was used. RESULTS: A total of 313 patients were analyzed. Thirty-four patients < or =20 weeks' gestation were followed until delivery: five (14.7%) developed preeclampsia; none had abnormal alpha-hCG levels before onset of preeclampsia. Patients with preeclampsia (21-30 weeks' gestation) demonstrated a mean alpha-hCG level greater than that of normotensive controls but this was not statistically significant. Between 31 and 40 weeks' gestation, mean alpha-hCG levels in the hypertensive and control groups were 210.8 ng/ml and 115.8 ng/ml, respectively (P < 0.001). A stronger association was observed between alpha-hCG and preeclampsia with increasing gestational age (relative risk [RR] 2.07, 21-30 weeks; RR 3.02, 31-40 weeks) and severity (RR 4.51, mild; RR 12.15, severe; RR 16.88, eclampsia). CONCLUSION: There is a strong association between alpha-hCG and preeclampsia, nevertheless this test is unsuitable for predicting preeclampsia.

Biomarkers↗

A controlled comparison of cognitive therapy and self-help support groups in the treatment of irritable bowel syndrome.

Thirty-four patients with irritable bowel syndrome were randomly assigned to 1 of 3 treatment conditions: individualized cognitive treatment (CT), self-help support group (SG), or symptom-monitoring waiting-list control (WL). Each of the 3 conditions lasted approximately 8 weeks. Pre- to posttreatment analyses revealed significantly greater reductions in both individual gastrointestinal (GI) symptoms and in a composite index for GI symptom change for the CT condition than for the SG or WL conditions. When compared with the SG and WL conditions, the CT condition also showed significant improvement on psychological measures of depression and anxiety. At 3-month follow-up, the results for the CT condition were maintained and revealed further numerical improvements.

Adult↗

Xeroderma pigmentosum group E binding factor recognizes a broad spectrum of DNA damage.

Xeroderma pigmentosum complementation group E binding factor (XPE-BF) is a damaged DNA binding protein that is deficient in a subset of patients from complementation group E of xeroderma pigmentosum. The protein recognizes various forms of DNA damage including some cyclobutane pyrimidine dimers, 6-4 photoproducts, cis-diamminedichloroplatinum(II) adducts, and single-stranded DNA. We now show that it also recognizes damage induced by nitrogen mustard; N-methyl-N'-nitro-N-nitrosoguanidine, and depurination, but has no detectable affinity for DNA adducts generated by trans-diamminedichloroplatinum(II), 4-nitroquinoline-N-oxide, 8-methoxypsoralen, or enzymatically methylated cytosine and adenine. The failure to recognize 4-nitroquinoline-N-oxide and 8-methoxypsoralen adducts is consistent with previous reports that XPE cells carry out wild-type levels of repair synthesis after DNA damage by those drugs. These results demonstrate that XPE-BF is a versatile damage recognition protein, but suggest that other proteins must contribute to the recognition of DNA lesions for the human excision repair pathway.

4-Nitroquinoline-1-oxide↗

Effects of recombinant human Steel factor (c-kit ligand) on early cord blood hematopoietic precursors.

The purpose of this study was to define the effects of recombinant human Steel factor (rhSF) (c-kit ligand) on early and late cord blood hematopoietic progenitors. In the presence of recombinant human erythropoietin (rhEpo), rhSF supported the development of granulocyte/macrophage, erythroid, and mixed colonies from CD34-positive cord blood cells. With increasing concentrations of rhSF, an increase in the number of mixed colonies was observed. This increase was paralleled by a decrease in the number of erythroid colonies, such that the total number of the two colony types was always constant. Similar results were observed when CD34+ cells were cultured in the presence of a combination of rhEpo, rhSF, and rhIL-3. These results indicate that the presence of rhSF enhanced the detectability of the nonerythroid components of mixed colonies. The effect of rhSF on early progenitors (pre-colony-forming units [pre-CFU]) was studied in a two-step assay. In this assay, cells positive for CD34 and resistant to treatment with 4-hydroperoxycyclophosphamide (CD34+/4-HCres) were cultured in suspension for 7 days with rhSF, rhIL-3, or rhSF plus rhIL-3 and then plated in clonogenic assays. Before suspension culture, CD34+/4-HCres cells had a low clonogenic potential (0.37%). After being cultured in suspension, however, these cells gave rise to a large number of colonies of all types when replated. Cells cultured in suspension with the combination of rhSF and rhIL-3 increased significantly in number and gave rise to more colonies, when compared to cells cultured with either factor alone (synergistic effect). In identical experiments, such as effect had not been observed with combinations of rhIL-3 and either rhIL-1 or rhIL-6. Thus, rhSF supports the expansion and differentiation of early progenitors in human cord blood.

Antigens, CD↗

Prediction of outcome from cognitive-behavioral treatment of irritable bowel syndrome.

The presence of a diagnosable Axis I psychiatric disorder predicted significantly (P less than 0.001) lower likelihood of significant improvement among 90 irritable bowel syndrome patients given cognitive and behavioral treatments to help the disorder. Other psychological tests, including the MMPI, BDI, STAI, as well as demographic variables, failed to yield significant prediction.

Adolescent↗

Physiological reactivity to stressors in irritable bowel syndrome patients, inflammatory bowel disease patients and non-patient controls.

Irritable Bowel Syndrome (IBS) patients were compared with Inflammatory Bowel Disease (IBD) patients and non-patient controls on four separate physiological measures (heart rate, finger-tip temperature, skin resistance level, and forehead EMG) for their physical reactivity to 'laboratory stressors'. It was predicted that the IBS patients would respond to these stressors with more physiological reactivity than the two other groups. There were initial basal differences among the groups on heart rate and finger-tip temperature: in general, the IBS patients had lower basal heart rates and the non-patient controls had lower finger-tip temperatures. These findings are contrary to the previous body of literature regarding possible sympathetic nervous system (SNS) arousal states in the IBS patient. The results also indicated IBS patients were not significantly different than the IBD patients or the non-patient controls in their reactivity to stressors. Previous literature has suggested that IBS in their reactivity to stressors. Previous literature has suggested that IBS patients have an enhanced SNS arousal or an SNS mediated reactivity to environmental stressors, our current study has not found these results.

Adult↗

Heliotropium europaeum poisoning of sheep with low liver copper concentrations and the preventive efficacy of cobalt and antimethanogen.

In a field experiment in the Mallee district of Victoria, Merlno xBorder Leicester ewes and wethers grazed Heliotropium europaeum (heliotrope) over periods of 3 to 4 months in 4 successive years. By the end of the second year 12% (14 of 120) of the sheep had died; after 4 years the loss attributable to heliotrope was between 18% and 35%. Mortality was not affected by intraruminal treatment with cobalt or antimethanogen. At the end of the experiment the highest concentration of copper in the liver was 1.95 mmol/kg wet weight (approximately 413 micrograms/g dry weight). The relatively low mortality from primary heliotrope poisoning and the low concentration of copper in the liver of sheep grazing the plant are discussed in relation to the contrasting situation that prevails in the Riverina area of New South Wales. The importance of local environmental factors in the management of heliotrope grazing by sheep is emphasised, particularly in relation to the number of seasons in which the plant may be a major component of the diet.

Alkanesulfonates↗

Waterborne outbreak of Campylobacter jejuni in Christchurch: the importance of a combined epidemiologic and microbiologic investigation.

Campylobacter is a common cause of gastroenteritis in New Zealand; however, the source of infection usually remains unknown. Reports of two cases of Campylobacter jejuni enteritis at a camp and convention centre near Christchurch were investigated. Through interviews of persons living at or attending the camp, 42 additional cases were identified. Epidemiologic and microbiologic data strongly suggested the water supply as the source of infection. The combined epidemiologic and microbiologic investigation was useful in quickly defining the magnitude and source of the outbreak, allowing for rapid implementation of control measures.

Campylobacter Infections↗

A serological survey of rinderpest antibody in wildlife and sheep and goats in northern Tanzania.

An extensive serological survey for rinderpest antibody in wildlife, principally buffalo (Syncerus caffer), and sheep and goats has been undertaken in the previously endemic region of Northern Tanzania to determine whether or not the virus has continued to cycle in susceptible species since the last occurrence of overt disease in 1982. The results show that infection but not disease has occurred at least until 1987 in buffalo in parts of the Serengeti National Park but not in the other game areas of Tanzania where samples were taken. Sero-positive sheep and goats were widely distributed and have been found in 10 of the 14 districts sampled but there have been no reports of disease. These findings bring into question the possibility of eradicating the disease from Africa and continuous annual monitoring of this and other similar ecological zones will be required.

Animals↗

Analysis of HLA antigens on germ cells in human semen.

Nucleated cells other than sperm (NCOS) were isolated from human semen by centrifugation on a Ficoll density gradient. Using tissue-specific monoclonal antibodies (mAb) greater than 99% of the NCOS were found to be sperm cell precursors (SpP). These cells were tested for the expression of class I and II (DR, DP and DQ) HLA antigens by using specific mAb. The anti-HLA class I and II and anti-beta 2-microglobulin mAb reacted with less than 1% of the NCOS. This was demonstrated by indirect immunofluorescence microscopy and fluorescence-activated cell sorter analysis. These results were similar to those obtained from testing germ cells in frozen sections of normal adult testis using the same panel of mAb. In mixed lymphocyte-NCOS cultures, the SpP failed to stimulate allogeneic lymphocytes even when different concentrations of cells were used. These results indicate little or no expression of HLA class I and II including the HLA-D (T cell-defined) determinant on the SpP, a phenomenon which could be of biological importance.

Antibodies, Monoclonal↗