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Biomedical subjects

C Welch

Publications and source records attributed to C Welch.

At least 19 recordsLinked to original sources

Influences of vermicomposts on field strawberries: 1. effects on growth and yields.

Vermicomposts processed commercially from food wastes and paper wastes were applied, to 4.5 m(2) field plots, under high plastic hoop tunnels, at rates of 5 or 10 tha(-1) to evaluate their effects on the growth and yields of strawberries (Fragaria ananasa) var. 'Chandler'. The vermicomposts were incorporated into the top 10 cm of soil and supplemented, based on chemical analyses, with amounts of inorganic NPK fertilizers calculated to equalize the initial fertilizer rates of 85-155-125 kgha(-1) NPK applied to the inorganic fertilizer plots. All treatments were replicated four times, in a completely randomized design, at two field sites on Doles silt loam or Hoytville silty clay loam at Piketon and Fremont, Ohio, respectively. Vermicompost applications increased strawberry growth and yields significantly; including increases of up to 37% in leaf areas, 37% in plant shoot biomass, 40% in numbers of flowers, 36% in numbers of plant runners and 35% in marketable fruit weights. These responses seemed not to be dose-dependent, since strawberries at one site grew fastest and yielded most in response to the 10 tha(-1) vermicompost application rate, whereas they responded positively and similarly to both the 5 and 10 tha(-1) rates of applications at the other site. These responses could not have been mediated by availability of macronutrients, since all plots were supplemented with inorganic fertilizers, to equalize macronutrient inputs for all treatments, but based on other research in our laboratory could have been due to production of plant growth regulators by microorganisms during vermicomposting.

Agriculture↗

Ultracision in gynaecological laparoscopic surgery.

The Ultracision harmonic scalpel and laparosonic coagulating shears use high-frequency ultrasound energy and can be used as a substitute for electrosurgery, lasers and steel scalpels in both laparoscopic and conventional gynaecological surgery. Its unique mechanism of action allows cutting and coagulation without causing a significant rise in temperature at the tissue level. Its safety has been tested extensively in animal experiments and there is now ample evidence to suggest that it produces less thermal damage in vitro compared to electrosurgery and lasers. Although these results have been extrapolated to human beings, there are no in vivo studies in humans to corroborate the above observations. This review highlights the mechanism of action, tissue effects, safety aspects, applications, versatility and limitations of this novel technique. The many advantages demonstrated by this instrument over other energy sources used in laparoscopic surgery should make it more popular in forthcoming years.

Female↗

Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes.

Recently, ATP-binding cassette transporter A1 (ABCA1), the defective molecule in Tangier disease, has been shown to stimulate phospholipid and cholesterol efflux to apolipoprotein A-I (apoA-I); however, little is known concerning the cellular cholesterol pools that act as the source of cholesterol for ABCA1-mediated efflux. We observed a higher level of isotopic and mass cholesterol efflux from mouse peritoneal macrophages labeled with [(3)H]cholesterol/acetyl low density lipoprotein (where cholesterol accumulates in late endosomes and lysosomes) compared with cells labeled with [(3)H]cholesterol with 10% fetal bovine serum, suggesting that late endosomes/lysosomes act as a preferential source of cholesterol for ABCA1-mediated efflux. Consistent with this idea, macrophages from Niemann-Pick C1 mice that have an inability to exit cholesterol from late endosomes/lysosomes showed a profound defect in cholesterol efflux to apoA-I. In contrast, phospholipid efflux to apoA-I was normal in Niemann-Pick C1 macrophages, as was cholesterol efflux following plasma membrane cholesterol labeling. These results suggest that cholesterol deposited in late endosomes/lysosomes preferentially acts as a source of cholesterol for ABCA1-mediated cholesterol efflux.

ATP-Binding Cassette Transporters↗

Zotepine in the prevention of recurrence: a randomised, double-blind, placebo-controlled study for chronic schizophrenia.

RATIONALE: Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia. Antipsychotic drugs also require to be effective in prevention of recurrence. OBJECTIVE: This trial was designed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia. METHODS: The study was a double-blind, parallel group, 26-week comparison of zotepine (300 mg daily, with fall back to 150 mg if necessary) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months. The primary outcome measure was the time to recurrence. Other evaluations included the brief psychiatric rating scale (BPRS), the scale for the assessment of negative symptoms (SANS), the clinical global impression (CGI) severity and improvement scales, and the Simpson and Angus scale for extrapyramidal symptoms (EPS). RESULTS: Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients (4 versus 21, respectively). The estimated 26-week risk of recurrence was six times lower for zotepine than placebo (8.7% versus 52.8%; hazard ratio 0.16, 95% CI 0.053, 0.484; P<0.001). Scores on the BPRS and CGI supported the efficacy of zotepine. There was no difference between the treatments with respect to EPS. CONCLUSIONS: Zotepine is effective in preventing recurrence in patients with chronic schizophrenia. The level of EPS was not different between zotepine and placebo.

Adolescent↗

Penciclovir cream for the treatment of sunlight-induced herpes simplex labialis: a randomized, double-blind, placebo-controlled trial. Penciclovir Cream Herpes Labialis Study Group.

OBJECTIVE: The purpose of this study was to further define the therapeutic value of penciclovir cream in the treatment of sunlight-induced herpes labialis by comparing its efficacy and tolerability with those of an inactive control (purified water). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group clinical trial, lesions were induced by exposure to sunlight. Treatment was self-initiated within 1 hour of development of the signs or symptoms of a recurrence. RESULTS: Healthy male and female patients (mean age, 38.3 years; range, 18 to 81 years) who had a history of sunlight-induced herpes labialis (mean of 6 recurrences in previous 12 months) applied either penciclovir cream (n = 266) or purified water (n = 275). Penciclovir cream significantly decreased the time to lesion healing (P < 0.001), with a reduction in median time of up to 2 days. The efficacy of penciclovir cream was further supported by a significant reduction in maximum lesion area (P = 0.008), a faster loss of lesion-associated symptoms (P = 0.026), and significant reductions in daily assessments of pain (P < or = 0.040), itching (P < or = 0.032), burning (P < or = 0.028), and tenderness (P < or = 0.026) as moderate or severe. These effects were reinforced by the results of the daily self-assessment of lesion attributes, with significantly fewer severe/extreme assessments of lesion size (P < or = 0.003), noticeability (P < or = 0.003), amount of scab/crust (P < or = 0.003), raised/ swollen area (P < or = 0.040), soreness/tenderness (P < or = 0.043), and overall severity (P < or = 0.001) throughout the study period. CONCLUSIONS: Penciclovir cream has demonstrated efficacy for a broad range of clinically important outcomes. Significant effects on lesion area, lesion symptoms, and other lesion attributes extend the clinical efficacy of penciclovir cream beyond lesion healing.

Acyclovir↗

A placebo-controlled comparison of zotepine versus chlorpromazine in patients with acute exacerbation of schizophrenia.

OBJECTIVE: The aim of this study was to evaluate the efficacy of zotepine in the treatment of acute episodes of schizophrenia. METHOD: Patients with acute exacerbation of schizophrenia (DSM-III-R criteria; n = 158) were allocated on a random, double-blind basis to receive zotepine (150 or 300 mg/day), chlorpromazine (300 or 600 mg/day) or placebo for 8 weeks. Symptoms were assessed on the BPRS, SANS and CGI scales at baseline and weeks 1, 2, 4, 6 and 8 and patients were assessed at these times for adverse effects. Analysis was by analysis of variance on the intent-to-treat population, with last observation carried forward. RESULTS: Mean BPRS scores improved statistically significantly more with zotepine than chlorpromazine (point estimate of difference -12.4, 95% CI -18.3 to -6.5) or placebo (point estimate of difference -12.7, 95% CI -18.6 to -6.8). Zotepine produced significantly fewer extrapyramidal symptoms (EPS) than chlorpromazine. CONCLUSION: Zotepine is an effective antipsychotic with low propensity for EPS.

Acute Disease↗

Altered gene expression pattern in the fatty liver dystrophy mouse reveals impaired insulin-mediated cytoskeleton dynamics.

The mouse fatty liver dystrophy (fld) mutation is characterized by transient hypertriglyceridemia and fatty liver during the neonatal period, followed by development of a peripheral neuropathy. To uncover the metabolic pathway that is disrupted by the fld mutation, we analyzed the altered pattern of gene expression in the fatty liver of fld neonates by representational difference analysis of cDNA. Differentially expressed genes detected include a novel member of the Ras superfamily of small GTP-binding proteins, a novel Ser/Thr kinase, and several actin cytoskeleton-associated proteins including actin, profilin, alpha-actinin, and myosin light chain. Because these proteins have a potential functional link in the propagation of hormone signals, we investigated cytoskeleton dynamics in fld cells in response to hormone treatment. These studies revealed that preadipocytes from fld mice exhibit impaired formation of actin membrane ruffles in response to insulin treatment. These findings suggest that the altered mRNA expression levels detected in fld tissue represent a compensatory response for the nonfunctional fld gene and that the fld gene product may be required for development of normal insulin response.

Amino Acid Sequence↗

Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene.

Scavenger receptor type B class I (SR-BI), initially identified as a receptor that recognizes low density lipoprotein (LDL), was recently shown to mediate the selective uptake of high density lipoprotein (HDL) cholesteryl esters in liver and steroidogenic tissues. To evaluate effects on atherosclerosis, transgenic mice with liver-specific overexpression of SR-BI (SR-BI Tg mice) have been crossed onto LDL receptor-deficient backgrounds. To induce atherosclerosis in a setting of moderate hypercholesterolemia, heterozygous LDL receptor-deficient mice (LDLR1) were fed a high fat/cholesterol/bile salt diet, and homozygous LDL receptor knock-outs (LDLR0) were fed a high fat/cholesterol diet. LDLR1/SR-BI Tg mice showed decreases in VLDL, LDL, and HDL cholesterol and a significant 80% decrease in mean lesion area in the aortic root compared with LDLR1 mice (female LDLR1 74, 120 micrometers(2) versus LDLR1/SR-BI Tg 12, 667 micrometers(2); male 25, 747 micrometers(2)++ versus 5, 448 micrometers(2), respectively). LDLR0/SR-BI Tg mice showed decreased LDL and HDL cholesterol but increased VLDL cholesterol and no significant difference in extent of atherosclerosis compared with LDLR0 mice. Combined data analysis showed a strong correlation between atherosclerotic lesion area and the VLDL+LDL cholesterol level but no correlation with HDL level. These studies demonstrate a strong anti-atherogenic potential of hepatic SR-BI overexpression. In mice with marked overexpression of SR-BI, the protective effect appears to be primarily related to the lowering of VLDL and LDL cholesterol levels.

Animals↗

Intracranial haemodynamics during attenuated responses to electroconvulsive therapy in the presence of an intracerebral aneurysm.

OBJECTIVES: This report describes successful anaesthesia and electroconvulsive therapy (ECT) in a patient with an unruptured basilar artery aneurysm. ECT is associated with a hyperdynamic state characterised by arterial hypertension, tachycardia, and considerably increased cerebral blood flow rate and velocity. These responses pose an increased risk for subarachnoid haemorrhage when an intracranial aneurysm coexists. METHODS: A 54 year old woman presented for ECT. She had a 20 year history of major depression which was unresponsive to three different antidepressant drugs. There was also an unruptured 5 mm saccular aneurysm at the basilar tip, which had been documented by cerebral angiography, but its size had remained unchanged for the previous four years. After she declined surgical intervention, she gave informed consent for ECT. During a series of seven ECT sessions middle cerebral artery flow velocity was recorded by a pulsed transcranial Doppler ultrasonography system. She was pretreated with 50 mg oral atenolol daily, continuing up to the day of the last ECT and immediately before each treatment, sodium nitroprusside was infused at a rate of 30 microg/min, to reduce systolic arterial pressure to 90-95 mm Hg. RESULTS: Systolic flow velocity during the awake state ranged from 62-75 cm/s, remaining initially unchanged with sodium nitroprusside infusion. After induction of anaesthesia (0.5 mg/kg methohexitone and 0.9 mg/kg succinylcholine), flow velocities decreased to 39-54 cm/s, reaching maximal values of 90 cm/s (only 20% above baseline) after ECT. These flow velocities recorded post-ECT were considerably below the more than twofold increase recorded when no attenuating drugs were used. Systolic arterial blood pressure reached maximal values of 110-140 mm Hg and heart rate did not exceed 66 bpm. Rapid awakening followed each treatment, no focal or global neurological signs were apparent, and the patient was discharged in remission. CONCLUSION: In a patient with major depression and a coexisting intracerebral saccular aneurysm who was treated with ECT, the combination of beta blockade with atenolol and intravenous infusion of sodium nitroprusside prevented tachycardia and hypertension, and greatly attenuated the expected increase in flow velocity in the middle cerebral artery.

Basilar Artery↗

Complex genetic control of HDL levels in mice in response to an atherogenic diet. Coordinate regulation of HDL levels and bile acid metabolism.

Inbred strains of mice differ in susceptibility to atherogenesis when challenged with a high fat, high cholesterol diet containing 0.5% cholic acid. Studies of recombinant inbred (RI) strains derived from the susceptible strain C57BL/6J (B6) and the resistant strains C3H/HeJ (C3H) and BALB/cJ have revealed an association between fatty streak lesion size and a decrease in high density lipoprotein (HDL) levels on the diet. To better understand the genetic factors contributing to HDL metabolism and atherogenesis in response to the diet, we studied mice derived from an intercross between B6 and C3H using a complete linkage map approach. A total of 185 female progeny were typed for 134 genetic markers spanning the mouse genome, resulting in an average interval of about 10 cM between markers. A locus on distal chromosome 1 containing the apolipoprotein AII gene was linked to HDL-cholesterol levels on both the chow and the atherogenic diets, but this locus did not contribute to the decrease in HDL-cholesterol in response to the diet. At least three distinct genetic loci, on chromosomes 3, 5, and 11, exhibited evidence of linkage to a decrease in HDL-cholesterol after a dietary challenge. Since a bile acid (cholic acid) is required for the diet induced changes in HDL levels and for atherogenesis in these strains, we examined cholesterol-7-alpha hydroxylase (C7AH) expression. Whereas B6 mice exhibited a large decrease in C7AH mRNA levels in response to the diet, C3H showed an increase. Among the intercross mice, multiple loci contributed to the regulation of C7AH mRNA levels in response to the diet, the most notable of which coincided with the loci on chromosomes 3, 5, and 11 controlling HDL levels in response to the diet. None of these loci were linked to the C7AH structural gene which we mapped to proximal chromosome 4. These studies reveal coordinate regulation of C7AH expression and HDL levels, and they indicate that the genetic factors controlling HDL levels are more complex than previously suggested by studies of RI strains. Furthermore, we observed that two of the loci for C7AH expression contributed to differences in gallstone formation between these strains.

Animals↗

Interaction of diet and genes in atherogenesis. Report of an NHLBI working group.

Recent advances in genetics and information emerging from the Human Genome Project make it feasible to examine the importance of dietary-genetic interactions in the development of atherosclerosis. In the opinion of the Working Group, three approaches are necessary to examine this concern. The first approach utilizes animal models to map and identify candidate genes involved in dietary responsiveness and atherogenesis. The second approach involves the evaluation of these genes in specific physiological processes involved in dietary responsiveness and atherogenesis. Finally, the third approach is to extend the studies performed in animal models to human populations using linkage or association studies.

Animals↗

Mitogenic activities of amino acid substitution mutants of staphylococcal enterotoxin B in human and mouse lymphocyte cultures.

Site-directed mutagenesis has been used to introduce amino acid substitutions at specific residues of the staphylococcal enterotoxin B (SEB) gene cloned from Staphylococcus aureus 10-275. The mitogenic activities of these derivatives were determined in two assay systems: (i) mouse spleen cells and (ii) a mixture of human peripheral blood mononuclear cells and lymphocytes. Substitution of either His-12, His-32, His-121, His-166, Lys-152, or Gly-205 did not significantly alter the mitogenic activity from that of the wild-type toxin in either proliferation assay. Substitution of either residue Asn-23, Phe-44, or Cys-93 reduced the mitogenicity of SEB by a degree that depended upon the assay system used. Similar to the results reported by others measuring toxin activation of mouse lymphoid cells, we found that substitutions of these three residues of SEB caused at least 800-fold reductions of mitogenic activity from that of the wild-type toxin. When tested for toxicity in vivo in D-galactosamine-treated mice, the reduced activities of these mutant toxins, however, were not as pronounced. In contrast, when tested in the human cell mitogenicity assay, these mutant toxins were active. Small alterations in activity (two- to fivefold reduction) were observable only at low concentrations. Our findings reveal the importance of using human lymphocytes in addition to the traditional mouse spleen cell assay when assessing biological activities of staphylococcal enterotoxins.

Animals↗