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Biomedical subjects

J B Collins

Publications and source records attributed to J B Collins.

10 recordsLinked to original sources
PubMed2026

Methods for single-pair Ascaridia galli genetic crosses.

Ascarid parasites infect a wide range of hosts, causing significant clinical and economic impacts. However, genetic tools for studying ascarid biology remain limited. We optimized genetic crosses using Ascaridia galli , a common ascarid of chickens. Sexually immature larval parasites were recovered from donors, transferred to gelatin capsules, and then given orally to recipients. We successfully established single-pair matings in 32% of crossing attempts. This method to control genetic crosses further establishes the avian model for ascarid research and will enable future studies to create a high-quality reference genome, inbreed anthelmintic resistant and sensitive lines, and investigate host-pathogen interactions.

Journal Article↗
PubMed2025

Naturally occurring variation in a cytochrome P450 modifies thiabendazole responses independently of beta-tubulin.

Widespread anthelmintic resistance has complicated the management of parasitic nematodes. Resistance to the benzimidazole (BZ) drug class is nearly ubiquitous in many species and is associated with mutations in beta-tubulin genes. However, mutations in beta-tubulin alone do not fully explain all BZ resistance. We performed a genome-wide association study using a genetically diverse panel of Caenorhabditis elegans strains to identify loci that contribute to resistance to the BZ drug thiabendazole (TBZ). We identified a quantitative trait locus (QTL) on chromosome V independent of all beta-tubulin genes and overlapping with two promising candidate genes, the cytochrome P450 gene cyp-35D1 and the nuclear hormone receptor nhr-176. Both genes were previously demonstrated to play a role in TBZ metabolism. NHR-176 binds TBZ and induces the expression of CYP-35D1, which metabolizes TBZ. We generated single gene deletions of cyp-35D1 and nhr-176 and found that both genes play a role in TBZ response. A predicted high-impact lysine-to-glutamate substitution at position 267 (K267E) in CYP-35D1 was identified in a sensitive strain, and reciprocal allele replacement strains in different genetic backgrounds were used to show that the lysine allele conferred increased TBZ resistance. Using competitive fitness assays, we found that neither allele was deleterious, but the lysine allele was selected in the presence of TBZ. Additionally, we found that the lysine allele significantly increased the rate of TBZ metabolism compared to the glutamate allele. Moreover, yeast expression assays showed that the lysine version of CYP-35D1 had twice the enzymatic activity of the glutamate allele. To connect our results to parasitic nematodes, we analyzed four Haemonchus contortus cytochrome P450 orthologs but did not find variation at the 267 position in fenbendazole-resistant populations. Overall, we confirmed that variation in this cytochrome P450 gene is the first locus independent of beta-tubulin to play a role in BZ resistance.

Animals↗
PubMed1991

Sexual dysfunction, social maladjustment, and psychiatric disorders in women seeking treatment in a premenstrual syndrome clinic.

The NIMH Diagnostic Interview Schedule (n = 43), and the Hopkins Symptom Checklist and Weissman Social Adjustment Scale (n = 35) was administered to assess the prevalence of psychiatric disorders and psychosocial maladjustment present in women seeking treatment in a multidisciplinary Premenstrual Syndrome Clinic. We found a 67 percent lifetime prevalence of DIS/DSM-III psychiatric disorders: 50 percent Major Affective Disorder (primarily Depression), 53 percent Anxiety Disorder (primarily Phobias or Generalized Anxiety Disorder), and 40 percent Psychosexual Dysfunction (notably Inhibited Sexual Desire or Excitement). Our group had significantly greater Major Depression, Dysthymia, and any one psychiatric disorder compared with female general population samples. Two-thirds of women with premenstrual symptoms had true Premenstrual Syndrome. In our sample, social maladjustment as well as psychiatric symptomatology was significantly greater than in normals and closer to that in psychiatric out-patient norms, and was independent of cycle phase. Presence or absence of PMS, social maladjustment and sexual dysfunction was each not significantly different in women with or without psychiatric disorder.

Adult↗
PubMed1988

Menopause.

The body of evidence now swings the scale toward the benefit of HRT for women beginning at the menopause. Based on newer studies, the risks for osteoporosis, cardiovascular morbidity, breast carcinoma, symptomatic vasomotor and anatomic changes occurring postmenopausally outweigh the risks of hormone replacement therapy in the end of the 20th century. Women should be instructed in adequate calcium intake, 1000 mg per day premenopausally and 1500 mg per day postmenopausally. Osteoporotic, breast carcinoma, and cardiovascular risks should be investigated at age 35 with appropriate lab screening, including lipoprotein analysis. Screening mammography should begin at age 40, continuing every 5 years until age 50, and yearly between ages 50 and 65. A diet high in calcium, low in cholesterol and fat, and a weight reduction program should be made available as early as possible and continued indefinitely. HRT should be made available beginning at menopause and continued to age 70. Moderate exercise should be encouraged at all ages. The next 5 to 10 years will answer some of the questions about the benefits of long-term HRT postmenopausally, especially with respect to its influence on cardiovascular risk. New progestational agents will probably be developed that will have fewer adverse effects on lipid profiles, while maintaining the protective effect on the endometrium and breast and further influencing the benefits of HRT postmenopausally. Modern medicine certainly cannot ensure living forever. The body of knowledge now available can modify the major causes for morbidity and mortality as the baby boom population reaches their middle age and golden years.

Estrogens↗
PubMed1987

Comparison of ketanserin and metoprolol in the treatment of essential hypertension.

Ketanserin, a serotonin receptor antagonist (S2), lowered blood pressure in patients with essential hypertension; at three months 72% (13/18) had a successful reduction in pressure. No marked orthostatic changes were noted. Older patients responded better when standing. Compared with metoprolol, ketanserin provided no significant difference in response at three months. With ketanserin, the heart rate was reduced only in the supine position, whereas it was reduced in the supine and standing positions with metoprolol. Response to ketanserin could not be predicted from baseline renin, aldosterone, or cortisol levels in blood, nor were there any changes in these factors or in plasma hydroxyindole levels with therapy. Ketanserin was generally well tolerated. Cholesterol values were significantly reduced with ketanserin, and there were no adverse hematologic or biochemical changes. Ketanserin should have a significant role in managing hypertension.

Blood Pressure↗
PubMed1986

Antihypertensive efficacy of pinacidil--automatic ambulatory blood pressure monitoring.

Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62 +/- 18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128 +/- 28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.

Adult↗