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Biomedical subjects

J Evans

Publications and source records attributed to J Evans.

At least 289 records · Page 16Linked to original sources
PubMed1994

Effect of inhibition of nitric oxide synthesis on vasopressin secretion in conscious rabbits.

NO synthase is present in magnocellular neurons of supraoptic and paraventricular nuclei as well as in the posterior pituitary gland and may participate in control of vasopressin secretion. To test this possibility, experiments were performed in conscious, chronically prepared rabbits to determine the effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on basal vasopressin secretion and vasopressin responses to increased plasma osmolality (hypertonic saline infusion; P osm) and decreased blood pressure (nitroprusside infusion). L-NAME infusion (0.5 mg.kg-1 x min-1 i.v.) increased mean arterial pressure [MAP; 82.6 +/- 3.4 to 93.0 +/- 3.0 mmHg (P < 0.02)], decreased heart rate [HR; 242 +/- 12 to 209 +/- 9 beats/min (P < 0.02)], decreased plasma renin activity [PRA; 3.1 +/- 0.6 to 2.0 +/- 0.6 ng.ml-.2 h-1 (P < 0.001)], and increased plasma vasopressin concentration [P AVP; 2.2 +/- 0.3 to 4.5 +/- 1.0 pg/ml (P < 0.05)]. P(osm) did not change. Hypertonic saline infusion did not change MAP or HR but decreased PRA [4.3 +/- 0.8 to 0.9 +/- 0.2 ng.ml-1 x 2 h-1 (P < 0.01)], increased P(osm) [284 +/- 1 to 305 +/- 2 mosmol/kg H2O (P < 0.001)], and increased PAVP [2.8 +/- 0.3 to 12.7 +/- 2.7 pg/ml (P < 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Intravascular platelet aggregation and spontaneous contrast.

The purpose of this study was to determine why spontaneous contrast developed after general anesthesia in dogs. Twenty-seven dogs underwent echocardiography before and after pentobarbital or chloralose-urethane general anesthesia. The results showed that none of the 12 dogs receiving pentobarbital and 10 of 15 dogs receiving chloralose-urethane anesthesia developed contrast, in association with large platelet and platelet-neutrophil aggregates (P < 0.01); this effect could also be reproduced in vitro. The administration of adenosine diphosphate or antiplatelet antibody to nine dogs confirmed that intravascular platelet aggregation can cause ultrasonic contrast. The implications of these findings for patients with spontaneous contrast are discussed.

Anesthesia, General↗
PubMed1994

The mesangium in the long-term remnant kidney model.

Hypertension, which develops during the course of the remnant kidney model (RK), plays a major role in the pathogenesis of glomerular injury. Morphologic studies have implicated mesangial injury and dysfunction in the pathogenesis of glomerular scarring in the hypertensive RK, but a separate role for mesangial injury has not been demonstrated in the absence of systemic hypertension. We studied glomerular injury and mesangial structure and function in a long-term (26 weeks) normotensive rat RK by using morphologic and morphometric studies and mesangial clearance of aggregated rate IgG (AggRaIgG). After right nephrectomy and infarction of two thirds of the left kidney (RK), the rats gained weight and developed mild but stable elevations of serum creatinine and urinary protein excretion as compared with the sham-operated controls (SHAM) over the course of the study. Systolic blood pressure was only mildly elevated (129 +/- 9 mm Hg versus 114 +/- 8 mm Hg, p < or = 0.05). Virtually all of the RK rats developed glomerular scarring, with segmental sclerosis in 8% +/- 8% and global sclerosis in 2% +/- 2% of the glomeruli, whereas the SHAM animals had no glomerular scarring, but we found limited morphologic evidence of mesangial cell injury in RK. The RK glomeruli were hypertrophied as compared with glomeruli in SHAM rats (glomerular diameter 199.3 +/- 15.2 microns versus 160.5 +/- 4.4 microns, p < or = 0.05), and the accompanying increase in capillary volume was caused by an increase in capillary length without a significant increase in diameter. Despite the glomerular hypertrophy and increased initial uptake in RK, the mesangial clearance of AggRaIgG was similar between RK and SHAM rats. We conclude that WKY rats with RK develop a progressive glomerulopathy characterized by segmental glomerulosclerosis, proteinuria, and mild hypertension. The normal mesangial clearance function and the absence of mesangial pathology in the hypertrophic remnant glomeruli mitigate against a role for mesangial injury in this form of experimental renal disease.

Animals↗
PubMed1993

Inclusion body formation and protein stability in sequence variants of interleukin-1 beta.

Inclusion body formation during recombinant protein expression in bacteria is of both fundamental interest and practical importance. To elucidate molecular mechanisms of this process, we are examining the in vitro folding and stability properties of a series of human interleukin-1 beta (IL-1 beta) sequence variants which exhibit widely differing tendencies to form inclusion bodies. Of 67 variants surveyed, nine, including wild type, were purified and their in vitro stability properties determined. One of these, a high inclusion body mutant, exhibited very low solubility in native buffer after purification and was not pursued further. For the other eight sequence variants, no strong correlations were observed between extent of inclusion body formation and either thermodynamic or thermal stability. In particular, a Lys97-->Val mutation produces substantially more IL-1 beta in inclusion bodies than the wild type (61 versus 8%) despite generating a protein more thermodynamically stable than wild type. Furthermore, the Lys97-->Val mutant forms substantial levels of inclusion bodies at 32 degrees C but requires incubation at temperatures greater than 48 degrees C for thermally induced aggregation in vitro. This and other data suggest that the tendency of at least some IL-1 beta variants to form inclusion bodies is most likely related to the stability or solubility of folding intermediates rather than native states. Implications of the structural locations of these mutations are also discussed.

Amino Acid Sequence↗
PubMed1993

Catecholamine uptake inhibitors elevate 6-hydroxydopamine in brain after administration of 6-hydroxydopa.

Desipramine and nomifensine, two norepinephrine uptake blockers, elevated by 63-248% the levels of 6-hydroxydopamine found in the frontal cortex at 1-4 h after administration of 6-OH-DOPA. Nomifensine also elevated 6-hydroxydopamine by 83% in the striatum at 4 h. These results nullify prior suggestions in the literature that 6-OH-DOPA is decarboxylated to 6-hydroxydopamine mainly outside of catecholamine nerve terminals and that 6-hydroxydopamine subsequently gains access to nerve terminals via the axonal membrane transport system for catecholamines.

Animals↗
PubMed1993

Reduction in incidence of optic nerve disease with annual ivermectin to control onchocerciasis.

The safety and efficacy of ivermectin in the prevention of blindness from onchocerciasis have been established in many studies that have addressed the drug's effects on the front of the eye. We undertook a study with sufficient statistical power to detect an effect on optic nerve disease (OND), probably the main cause of blindness in the disorder. The trial was based in 34 mesoendemic communities in Kaduna State, Nigeria. Villagers aged 5 years and older were randomly assigned annual dosing with ivermectin or placebo for 3 years. Participants underwent medical and ophthalmological examinations before the first, third, and fourth treatments. 3522 villagers aged 15 and older were re-examined at least once. Skin-snip samples were taken at baseline for calculation of microfilarial load. The outcome measure was development of disc pallor accompanied by objective evidence of deterioration in visual function; 116 subjects (45 ivermectin-treated, 71 placebo-treated) showed such changes during the trial. The incidence rate ratio (ivermectin vs placebo) was 0.90 (95% CI 0.54-1.51) for subjects with loads of 0-10 mf (microfilariae) per mg skin and 0.52 (0.29-0.93) for subjects with more than 10 mf/mg. The incidence rate ratio varied little when account was taken of age, sex, presence of pre-existing disc pallor in one eye, previous use of diethylcarbamazine citrate, or doses of ivermectin or placebo received. There was evidence that ivermectin reduced the incidence of OND in subjects with microfilarial loads above 10 mf/mg but had little effect in those with lower loads. Sustained annual delivery of ivermectin could prevent a substantial proportion of onchocercal blindness in mesoendemic communities.

Adolescent↗
PubMed1993

Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. RESULTS: Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. CONCLUSION: The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.

Administration, Oral↗
PubMed1993

Non-medical implications of malignant melanoma.

Insurance and mortgage companies continue to regard melanoma in a rigid and perhaps flawed way, with detrimental effect to patients' financial standing. We questioned 100 consecutive patients coming to our clinic between the ages of 20 and 50, and asked if they had had problems obtaining life insurance, mortgages etc, since they were diagnosed. A substantial proportion of patients in the younger age groups had problems with mortgage and insurance applications.

Adult↗
PubMed1993

Isolated complex limb reduction abnormality diagnosed antenatally.

Congenital limb reduction defects are rare lesions that are usually associated with other anomalies. Terminal defects are the commonest reduction defects. The aetiology seems to be multifactorial. We present a case of congenital terminal deficiency of the same side of the upper and lower limbs diagnosed by ultrasound scanning during the second trimester. The fetus had an absent right fibula and right foot, a hypoplastic right hand and left talipes equinovarus. The pregnancy was terminated. Micrognathia was the only associated anomaly found on postmortem examination. The cause of this isolated anomaly is unknown but, because of the very variable presentation of limb reduction defects, could possibly fit into the categories so far described in the literature.

Adult↗
PubMed1993

Lesch-Nyhan syndrome and the lower lip guard.

Lesch-Nyhan syndrome, a rare inborn error of metabolism, is characterized by mental retardation and factitious oral lesions, which cause immense difficulties in its management. A case of an 11-year-old boy, the elder of two siblings with this condition, who had severe self-inflicted injuries to oral and perioral tissues is presented highlighting the different treatment modalities considered. A tailor-made lipguard proved to provide the best cosmetic result short term.

Child↗
PubMed1993

Thymine ring saturation and fragmentation products: lesion bypass, misinsertion and implications for mutagenesis.

We have used thymine glycol and dihydrothymine as representative ring saturation products resulting from free-radical interaction with DNA pyrimidines, and urea glycosides and beta-ureidoisobutyric acid (UBA) as models for pyrimidine-ring fragmentation products. We have shown that thymine glycol and the ring-fragmentation products urea and beta-ureidoisobutyric acid, as well as abasic sites, are strong blocks to DNA polymerases in vitro. In contrast, dihydrothymine is not a block to any of the polymerases tested. For thymine glycol, termination sites were observed opposite the putative lesions, whereas for the ring-fragmentation products, the termination sites were primarily one base prior to the lesion. These and other data have suggested that thymine glycol codes for an A, and that a base is stably inserted opposite the damage, whereas when a base is inserted opposite the non-coding lesions, it is removed by the 3-->5 exonuclease activity of DNA polymerase I. Despite their efficiency as blocking lesions, thymine glycol, urea and UBA can be bypassed at low frequency in certain specific sequence contexts. When the model lesions were introduced individually into single-stranded biologically active DNA, we found that thymine glycol, urea, beta-ureidoisobutyric acid, and abasic sites were all lethal lesions having an activation efficiency of 1, whereas dihydrothymine was not. Thus the in vitro studies predicted the in vivo results. When the survival of biologically active single-stranded DNA was examined in UV-induced Escherichia coli cells where the block to replication was released, no increase in survival was observed for DNA containing urea or abasic sites, suggesting inefficient bypass of these lesions. In contrast, beta-ureidoisobutyric acid survival was slightly enhanced, and transfecting DNA containing thymine glycols was significantly reactivated. When mutation induction by unique lesions was measured using f1-K12 hybrid DNA containing an E. coli target gene, thymine glycols and dihydrothymine were found to be inefficient as premutagenic lesions, suggesting that in vivo, as in vitro, they primarily code for A. In contrast, urea and beta-ureidoisobutyric acid were efficient premutagenic lesions, with beta-ureidoisobutyric acid being about 4-5-fold more effective than urea glycosides, which have approximately the same rate of mutation induction as abasic sites from purines. Sequence analysis of the mutations resulting from these ring-fragmentation products shows that the mutations produced are both lesion and sequence context dependent. The possible roles that bypass efficiency and lesion-directed misinsertion might play in mutagenesis are discussed.

Base Sequence↗
PubMed1993

Site-specific properties of human adipose depots homologous to those of other mammals.

1. Mean adipocyte volume, collagen content and the maximum activities of hexokinase and phosphofructokinase were measure in 15 depots of 8 men who were in good health until their sudden death. The data were used to establish homologies between depots in humans and other mammals. 2. The basic organization of adipose tissue in humans is similar to that of other mammals, although additional depots that are minimal or absent in rodents may be massive in humans. 3. Known site-specific properties relevant to manipulation of adipose tissue are reviewed.

Abdominal Muscles↗