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Biomedical subjects

J Wade

Publications and source records attributed to J Wade.

At least 91 records · Page 5Linked to original sources
PubMed1994

Fadrozole: a potent and specific inhibitor of aromatase in the zebra finch brain.

Aromatase and 5 beta-reductase activity are expressed at high levels in the zebra finch brain, especially in the telencephalon. Aromatization of androgens to estrogens is thought to be a critical step in the organization and activation of avian sexual behaviors. In contrast, 5 beta-reductase is thought to be an inactivating enzyme, one that catalyzes the conversion of androgens to biologically inactive metabolites. To address the importance of aromatase activity in this system, it is necessary to find an effective and selective aromatase inhibitor, one that has little or no effect on other androgen-metabolizing enzymes. The potency and specificity of fadrozole hydrochloride as an aromatase inhibitor was tested in zebra finch telencephalon. The compound was tested in vitro in primary dissociated cell cultures made from hatching telencephalon and compared to a commonly used inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). Untreated, these cultures express extremely high levels of aromatase and 5 beta-reductase activity and therefore allow sensitive measurement of the effectiveness of inhibitors. Aromatase activity was also measured in homogenates of adult telencephalon following in vivo fadrozole injection. Finally, aromatase and 5 beta-reductase activity were quantified in zebra finch telencephalon following similar intramuscular injections in 4- to 6-day-old birds. In all three cases, fadrozole was highly effective in reducing aromatase activity. Fadrozole increased 5 beta-reductase activity, presumably due to an increase in available substrate, but had no inhibitory effect on the enzyme. ATD was less effective in inhibiting aromatase, and it also inhibited 5 beta-reductase activity at high concentrations.

Androstatrienes↗
PubMed1994

Profile of Caucasian women with possible genetic predisposition to reflex sympathetic dystrophy: a pilot study.

OBJECTIVES: To test possible human lymphocyte antigen (HLA) associations in subjects with reflex sympathetic dystrophy (RSD), and to determine correlation of HLA associations to treatment outcomes. DESIGN: Identification of class I (HLA-A, B, C) and class II (HLA-DR and DQ) (MHC) antigens by well-defined reagents in patients with RSD. SETTING AND PATIENTS: The HLA analysis was performed on 15 Caucasian women attending a university pain clinic and diagnosed with RSD on the basis of strict inclusion and exclusion criteria. OUTCOME MEASURES: Resistance to treatment was defined on the basis of lack of response to conservative management, failure to experience long-term symptom relief after sympathetic blocks, recurrence of pain after sympathectomy, need for palliative treatment, and degree of residual disability at the end of all treatments. RESULTS: A twofold increase of A3, B7, and DR2(15) MHC antigens was observed in the study population compared to control frequencies. Eighty (five of six) of DR2(15)-positive patients proved to be resistant to treatment. CONCLUSIONS: The results of this pilot study are the first to suggest a possible genetic diathesis in RSD patients with poor treatment outcome. If this finding can be confirmed in larger studies, strictly defined RSD could constitute the third neuroimmune disorder (besides multiple sclerosis and narcolepsy) associated with DR2(15). Gene(s) conferring susceptibility to RSD may be present within or near the MHC region of the short arm of chromosome 6. Due to the small size of our study group it is imperative that larger studies be done in RSD patients employing strict diagnostic criteria to confirm or refute our original observations.

Adolescent↗
PubMed1994

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

NSAIDs attenuate the natriuretic response to loop diuretics. Their effect on the action of distal tubular diuretics is poorly explored. Accordingly, the pharmacokinetics and pharmacodynamics of metolazone [M], a distal tubular diuretic, with and without indomethacin [M+I] or sulindac [M+S] were examined in six healthy volunteers. Urine samples were obtained over 36 hours post-metolazone dosing for the determination of sodium, potassium and metolazone concentration. Though cumulative M excretion 750 +/- 247 [mucg/36 h] [M]; 749 +/- 239 [M+I]; 848 +/- 443 [M+S] was comparable between treatment groups, total sodium [Na+] excretion was significantly depressed in the presence of S or I, 685 +/- 114 [mEq/36 h] [M]; 454 +/- 90 [M+I] (p < or = 0.05); 553 +/- 123 [M+S] (p < or = 0.05). Peak Na+ excretion [muEq/min] was significantly decreased by I only and time to peak Na+ excretion did not differ amongst treatment groups. Total potassium [K+] excretion 160 +/- 39 [mEq/36 h] [M]; 111 +/- 53 [M+I] (p < or = 0.05); 135 +/- 31 [M+S] significantly decreased with I. This phenomenon was most evident between 12 and 36 hours. The administration of I or S with M significantly blunted sodium excretion on a purely pharmacodynamic basis while the decline in urinary potassium excretion upon addition of I to M related probably to an attenuation of braking phenomenon induced kaliuresis. These findings likely reflect NSAID-induced sodium reabsorption at loci prior to the site of action of metolazone.

Administration, Oral↗
PubMed1993

The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

3T3 Cells↗
PubMed1993

Hormonal control of sex differences in the brain, behavior and accessory sex structures of whiptail lizards (Cnemidophorus species).

The effects of steroid hormones on sexual dimorphisms in the brain, behavior and accessory sex structures were investigated in two species of whiptail lizards. The studies were conducted both in adults and hatchlings of a sexually reproducing species (Cnemidophorus inornatus) and an all-female species (C. uniparens) which displays 'sexual' behaviors typical of males and females. Adults were gonadectomized and approximately 3 months later given either a Silastic capsule filled with sex steroid or an empty capsule. Young animals of both species were left intact and given a capsule on the day of hatching. An additional group of C. uniparens was ovariectomized on the day of hatching. Following treatment, measures of oviduct (estrogen-dependent), renal sex segment (androgen-dependent) and wolffian duct (androgen-dependent) hypertrophy were taken in some experiments. Animals were also tested for sexual behavior in some of the studies. The volumes of the anterior hypothalamus-preoptic area and ventromedial hypothalamus were measured in each individual. Estrogen, testosterone and dihydrotestosterone stimulated peripheral structures at both time periods in both sexes and species. The hormones also stimulated courtship and copulatory behaviors in many of the adult animals. However, testosterone in the anterior hypothalamus-preoptic area of male C. inornatus was the only treatment which produced parallel effects on the volume of a brain area and the behaviors which it controls. These data add whiptail lizards to the list of species in which steroid hormones affect the volume of brain regions in adulthood, but suggest that such changes in morphology are not necessarily predictive of functional differences.

Animals↗
PubMed1993

Gangrene of the anterior abdominal wall after orthotopic liver transplantation: invasive cutaneous candidiasis.

Fungal infections following liver transplantation are not uncommon and may be life-threatening. Superficial candidal infections of the bronchus, oesophagus and urinary tract are the most common mode of presentation. Invasive cutaneous and subcutaneous candidiasis is, however, very rare. We report two patients with invasive cutaneous and subcutaneous candidiasis after orthotopic liver transplantation.

Abdominal Muscles↗
PubMed1993

Prospective controlled trial of selective parenteral and enteral antimicrobial regimen in fulminant liver failure.

To compare the efficacy of a selective parenteral and enteral antimicrobial regimen in patients with fulminant liver failure, we classified 104 patients on reaching grade II encephalopathy as infected or non-infected. Patients who were infected were randomly assigned to receive IV cefuroxime (group 1) or selective parenteral and enteral antimicrobial regimen (group 2). Noninfected patients were randomly selected to receive either selective parenteral and enteral antimicrobial regimen (group 3) or no initial antimicrobials until clinically indicated (group 4). The four groups were comparable regarding age, sex, cause of disease, coma grade, international normalization ratio, presence of kidney failure and indicators of poor prognosis on admission to the study. Clinical parameters such as white cell count, temperature or changes in the chest radiograph, which were used to stratify patients into those infected or not, were not good predictors of infection because early infection rates were similar in the two groups. Three patients died within 24 hr and were excluded from the analysis. We found 42 microbiologically confirmed infections: group 1, 6 of 21; group 2, 8 of 21; group 3, 9 of 28; and group 4, 19 of 31. A reduction in infection was seen between groups 3 and 4 (p < 0.05). Patients receiving the selective parenteral and enteral antimicrobial regimen (groups 2 and 3) had fewer infections than the control group (group 4) (p < 0.005). Groups receiving early antimicrobial therapy (groups 1, 2 and 3) had a lower incidence of infection compared with group 4 (p < 0.0005). Overall, 55.5% survived, with no significant difference between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Sexual dimorphisms in the soma size of neurons in the brain of whiptail lizards (Cnemidophorus species).

Soma area was significantly larger in the anterior hypothalamus-preoptic area of male than female Cnemidophorus inornatus, and it was significantly larger in females than males in the ventromedial hypothalamus. These results parallel those on the volume of the brain areas in these animals, and therefore probably explain at least part of the dimorphisms seen in this sexually reproducing species. Soma size in parthenogenetic C. uniparens also parallels volume.

Animals↗
PubMed1992

An electronic method for measuring joint tenderness in rheumatoid arthritis.

OBJECTIVE: To test the precision of a new electronic method for measuring joint tenderness. METHOD: Joint tenderness was measured in 30 patients with rheumatoid arthritis, using an electronic dolorimeter. The results were compared with joint tenderness counts, which were made according to the American Rheumatism Association (ARA) methods. RESULTS: The intra-observer variability using the electronic method was significantly decreased compared with the conventional ARA joint tenderness counts. CONCLUSION: The electronic method is more efficient for use in clinical trials than is the conventional ARA joint tenderness count.

Arthritis, Rheumatoid↗
PubMed1992

An assessment of regeneration across peripheral nerve allografts in rats receiving short courses of cyclosporin A immunosuppression.

While peripheral nerve reconstruction could benefit from the use of nerve allografts, long term immunosuppression for non-vital organ transplantation is controversial. This study investigated the effectiveness of short course Cyclosporin A immunosuppression. Fourteen Lewis (RT1l) rats were the recipients of 3 cm sciatic nerve grafts from ACI (RT1a) donors, repaired to the transected sciatic nerve of the recipient animal. Animals were treated with Cyclosporin A (5 mg/kg/day) for eight weeks. Neuromuscular function was assessed every two weeks by sciatic function index determinations until 20 weeks. Electrophysiological, histological and morphological evaluations were performed at 14 (n = 6) and 20 weeks (n = 8) postengraftment. Rats had significantly improving functional studies from four to eight weeks (P = 0.01). Function decreased following cessation of Cyclosporin A treatment. Rats evaluated at 14 weeks had histological evidence of graft rejection with inflammatory cell infiltration, extensive demyelination and remyelination, and some Wallerian degeneration. Rats demonstrated improvement in morphological parameters and motor function from 14 to 20 weeks after engraftment. In this sciatic nerve allograft model, short course Cyclosporin A immunosuppression, although resulting in an initial episode of graft rejection, was successful in permitting good long term functional regeneration of neuromuscular function.

Animals↗
PubMed1992

The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: I. Histologic and electrophysiologic assessment.

Nerve regeneration across peripheral nerve allografts and control autografts in primates immunosuppressed with Cyclosporin A was quantitatively evaluated by electrophysiologic and histologic methods. Twelve cynomolgus monkeys received 3-cm autografts and allografts in contralateral ulnar nerves. They were immunosuppressed with Cyclosporin A at 25 mg/kg per day or placebo vehicle. Morphometric analysis of nerve graft and distal nerve segments was assessed at 1 year after engraftment. Quantitative electrophysiologic studies were performed percutaneously at 6 and 12 months, and compound action potentials were measured directly across the nerve grafts at 1 year. Excellent regeneration was seen across autografts and allografts in Cyclosporin A-treated and placebo-treated recipients.

Action Potentials↗
PubMed1992

The ability of schizophrenics to perceive and cope with negative affect.

Thirty-four schizophrenic patients in an acute in-patient hospital were compared with 24 in-patients with major affective disorder and 19 non-patient controls on a role-play test of social skills and a test of affect perception. The role-play test consisted of 12 simulated conversations in which the subject was confronted by parents and friends expressing high-EE criticism or non-critical dissatisfaction. Schizophrenic patients lacked assertiveness and social skills in all conditions, but they did not show any differential impairment when presented with high EE. They consistently lied and denied errors rather than responding assertively or apologizing, whether confronted with high-EE or benign criticisms. On the affect perception test, schizophrenic patients consistently underestimated the intensity or negativeness of negative emotions, but they were not deficient in perception of positive emotional displays. The data do not support the hypothesis that schizophrenic patients are poor at dealing with high-EE behaviours, but do indicate that their ability to cope with even mild negative affect is impaired. Possible explanations for this impairment include limited attentional capacity, a neurologically based perceptual deficit, and a self-protective mechanism to reduce or avoid stress.

Adaptation, Psychological↗
PubMed1992

Ten year survival of a patient with advanced pulmonary hypertension and mixed connective tissue disease treated with immunosuppressive therapy.

Pulmonary hypertension is the most frequent cause of death in patients with mixed connective tissue disease. The pulmonary hypertension is progressive and difficult to treat effectively. These patients experience considerable morbidity secondary to diminished cardiac function. We describe a case in which sequential administration of cyclophosphamide and cyclosporine A favorably altered the clinical and hemodynamic course of this serious complication.

Adult↗
PubMed1992

Residual efficacy of pirimiphos methyl (Actellic) on Anopheles sacharovi in Cukurova, Turkey.

Village-scale trials of 50% emulsifiable concentrate (EC) and 40% wettable powder (WP) formulations of pirimiphos methyl (Actellic) were carried out against Anopheles sacharovi in Cukurova, Turkey. Susceptibility tests with wild caught, gonoactive and composite aged An. sacharovi over a range of chemical concentrations resulted in 100% mortality after exposure for 60 min to a 0.5% active ingredient concentration. Surface treatments of Actellic 50% EC at 0.9 g/m2 caused a significant decrease in parous rate and a 96.9% reduction in resting density. Persistence on concrete, wood, zinc and plywood was still high at the time of the second spray round, more than 7 wk postspray and ranged from 73% (zinc) to 98% (plywood). More than 50% mortality was still recorded 8 wk postspray using 1.6 g/m2 WP on wood, plywood, zinc and thatch substrates.

Aerosols↗
PubMed1991

The conformation of porcine-brain natriuretic peptide by two-dimensional NMR spectroscopy.

Two-dimensional (2D) 1H-NMR spectra of porcine-brain natriuretic peptide (pBNP) have been recorded at 300 MHz and 400 MHz. Peak assignments have been made and the combined information from chemical shifts, coupling constants, temperature coefficients and NOEs have been used to determine the conformational properties of pBNP in (C2H3)2SO. Overall the peptide appears to be flexible, with the possibility of some beta-type structure near the C terminus. Some of the assignments and deduced structural features in the current study differ from those in a recent report by Inooka et al. [Inooka, H., Kikuchi, T., Endo, S., Ishibashi, Y., Wakimasu, M. and Mizuta, E. (1990) Eur. J. Biochem. 193, 127-134] which may indicate the sensitivity of the structure of this peptide to differences in solution conditions.

Amino Acid Sequence↗