Search PubMed⌕ Search

Biomedical subjects

T Taylor

Publications and source records attributed to T Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1991

Pharmacokinetics of the anti-leishmanian agent WR 6026 in dogs.

The pharmacokinetics of the anti-leishmanial agent WR 6026 (8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride) has been studied after single intravenous infusion and oral doses of 5 mg (base)/kg to 6 Beagle dogs. After single intravenous infusions of 15 min, plasma concentrations of unchanged drug declined bi-exponentially from a mean maximum of 1203 ng/ml +/- 277 SD at the end of infusion to the limit of quantitation during 16 hours. After single oral doses, the mean Cmax of 23 ng/ml +/- 14 SD occurred at a mean Tmax of 2.2 hours +/- 1.3 SD. During 72 hours after the intravenous and oral doses, 0.6% and less than 0.2% of the dose respectively was excreted unchanged in the urine. The mean terminal-life of WR 6026 after the infusion doses was +/- 0.3 SD, but after the oral doses, plasma concentrations of drug were too low to allow estimation of the terminal half-life. The systemic clearance of WR 6026 (43.5 ml/min/kg) greatly exceeded the nomina, plasma flow (ca. 22 ml/min/kg) and indicated considerable extra-hepatic and extra-renal elimination of WR 6026 in dogs. The mean systemic availability of WR 6026 after the oral doses was ca.4%. The mean volumes of distribution of WR 6026 in dogs were 3.3 litres/kg +/- 1.1 SD (V(ss)) and 7.7 litres/kg +/- 2.4 SD (V(area)). These data characterise WR 6026 as a drug of relatively high systemic clearance, large volume of distribution, relatively short half-life and low systemic availability, probably due to presystematic elimination in the liver.

Administration, Oral↗
PubMed1990

Isolation and characterization of the 32.5 kDa protein from the venom of an endoparasitic wasp.

The major venom proteins from the endoparasitic wasp were analyzed for distribution in the venom gland. A 32.5 kDa protein was purified from the venom gland of the Chelonus near curvimaculatus wasp. The protein accounts for about 25% of the total protein content of the venom and each gland contains 3-6 pmol of this component. The protein is acidic in nature and anion-exchange chromatography facilitated the purification of the protein to apparent homogeneity. On testing the purified protein by in vivo bioassay, it was found to elicit an effect comparable with the complete venom. The protein does not appear to have any disulfide bonds of major structural importance exposed under SDS-denaturing conditions. Products of chemical partial digest of the purified protein at the methionyl residues by cyanogen bromide were analyzed by SDS-PAGE. The 27.6 kDa fragment retained an epitope to an antibody raised against total Chelonus venom proteins, whereas no epitopes were detected for 4.9 and 0.6 kDa fragments.

Amino Acid Sequence↗
PubMed1990

Determination of benzydamine and its N-oxide in biological fluids by high-performance liquid chromatography.

A simple, sensitive and selective method for the determination of benzydamine in human plasma and urine, and for benzydamine N-oxide in urine, has been developed using high-performance liquid chromatography in the reversed-phase mode. The limit of reliable determination of benzydamine in plasma was 0.5 ng/ml and that in urine 1 ng/ml; the limit of reliable determination of benzydamine N-oxide in urine was 50 ng/ml. The method has been successfully applied to the analysis of these compounds in biological fluids after administration of intravenous and oral doses of benzydamine to human volunteers.

Benzydamine↗
PubMed1990

Effects of hysterectomy on bowel and bladder function.

A case control study compared the bowel habit of 91 post-hysterectomy women with paired controls from the same family doctor practice. More cases had an abnormal bowel frequency, a firmer stool consistency and assessed themselves as having abnormal bowel function, predominantly constipation after hysterectomy, than controls. Significantly more cases than controls had consulted a doctor because of constipation but there was no significant difference in laxative usage. There was a significant short-term association between decreased bowel frequency and increased urinary frequency after hysterectomy. This became highly significant in those patients who developed chronic symptoms. Oophorectomy, unilateral or bilateral, did not significantly affect bowel habit other than to intensify the change in stool consistency. The hypothesis is discussed that the post-hysterectomy effects on bowel and bladder function may have a common aetiology in a degree of autonomic denervation of both viscera.

Adult↗
PubMed1990

Genomic maps of some strains within the Mycoplasma mycoides cluster.

Genomic restriction maps for the small colony (SC) strains (PG1, KH3J, Gladysdale, and V5) of Mycoplasma mycoides subsp. mycoides (the agent of contagious bovine pleuropneumonia) and for Mycoplasma strain PG50 (classified as bovine serogroup 7), with respective sizes of 1,280, 1,280, 1,260, 1,230, and 1,040 kbp, were compared with the map (1,200 kbp) for a large colony strain (Y goat) of M. mycoides subsp. mycoides. The number and order of all mapped restriction sites were fully conserved in the SC genomes, as were the approximate positions of mapped loci. A number of these restriction sites in the Y genome and some, but fewer, in the PG50 genome appeared to be conserved. The SC and large colony strains shared conservation in the relative positions of the mapped loci, except for rpoC.

DNA Probes↗
PubMed1990

Thyroid hormone regulation of TRH mRNA levels in rat paraventricular nucleus of the hypothalamus changes during ontogeny.

The changing roles of the hypothalamus and pituitary in regulating thyroid hormone levels in the rat during ontogeny has not been fully elucidated. It has been reported that endogenous TRH begins to stimulate TSH secretion at 5-8 days after birth but that the pituitary responds to hypothyroidism during late gestation. To determine the onset and extent of TRH response to low thyroid hormone levels during ontogeny, normal and hypothyroid rats treated with methimazole for 7 days were sacrificed at 16 days gestation (E16), 20 days gestation (E20), 7, 21 and 56 days after birth (n = 5/study group). Plasma hormones were assayed from pregnant mothers, pups (pooled) and adults. Levels of TRH mRNA were measured in the paraventricular nuclei (PVN) by in situ hybridization histochemistry. A labeled 48-base cDNA oligonucleotide for TRH was hybridized with brain slices (n = 6/animal) in the region of the medial parvocellular division of the PVN of the hypothalamus and the signal was quantitated by digitized computer analysis. Plasma-free T4 levels decreased and plasma TSH levels increased in the animals treated with methimazole as compared to the euthyroid controls. TRH mRNA was detected in the PVN at E16 after brain slices were dipped in emulsion and granules observed by dark-field microscopy. In the euthyroid animals, TRH mRNA increased from E20 (150 +/- 9 OD units) to 7 days (222 +/- 5 OD units) and remained unchanged at 21 days (252 +/- 27 OD units) and 56 days (244 +/- 6 OD units).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The paraventricular nucleus of the hypothalamus has a major role in thyroid hormone feedback regulation of thyrotropin synthesis and secretion.

The role of the hypothalamic paraventricular nucleus (PVN) in thyroid hormone regulation of TSH synthesis during hypothyroidism was studied in adult male rats that were normal (n = 10), had primary hypothyroidism with sham lesions in the hypothalamus (n = 17), and had primary hypothyroidism with PVN lesions (n = 14). Two and 4 weeks after initiation of treatment, plasma levels of thyroid hormones (TSH, corticosterone and PRL) and pituitary content of TSH beta and alpha-subunit mRNA were measured. TRH mRNA levels in the PVN were determined by in situ hybridization histochemistry. At 2 weeks, despite a decrease in plasma free T4 in both hypothyroid groups, plasma TSH levels increased, but to a lesser degree, in the hypothyroid PVN lesioned compared to hypothyroid sham-lesioned group (7.8 +/- 1.3 vs. 20.5 +/- 1.1 ng/dl; P less than 0.05). Similarly, at 4 weeks, the hypothyroid PVN-lesioned group demonstrated a blunted TSH response compared to the hypothyroid sham-lesioned group (6.8 +/- 0.7 vs. 24.0 +/- 1.3 ng/dl; P less than 0.05). Plasma corticosterone and PRL did not significantly differ between sham-lesioned and PVN-lesioned groups. TSH beta mRNA levels markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls at 2 weeks (476 +/- 21% vs. 100 +/- 39%; P less than 0.05) and 4 weeks (1680 +/- 270% vs. 100 +/- 35%; P less than 0.05). In contrast, TSH beta mRNA levels did not increase with hypothyroidism in the PVN-lesioned group compared to those in euthyroid controls at 2 weeks (140 +/- 16%, P = NS) and only partially increased at 4 weeks (507 +/- 135; P less than 0.05). alpha mRNA levels at 4 weeks markedly increased in hypothyroid sham-lesioned rats compared to those in euthyroid controls (1121 +/- 226% vs. 100 +/- 48%; P less than 0.05), but did not increase in the hypothyroid PVN-lesioned rats (61 +/- 15%; P = NS). TRH mRNA in the PVN increased in the hypothyroid sham-lesioned rats compared to those in euthyroid controls (16.6 +/- 1.3 vs. 4.8 +/- 1.2 arbitrary densitometric units; P less than 0.05), and TRH mRNA was not detectable in the PVN of hypothyroid-lesioned rats at 2 weeks. In summary, lesions in rat PVN prevented the full increase in plasma TSH, pituitary TSH beta mRNA, and alpha mRNA levels in response to hypothyroidism. Thus, factors in the PVN are important in thyroid hormone feedback regulation of both TSH synthesis and secretion.

Animals↗
PubMed1990

Pre-translational and post-translational regulation of TSH: relationship to bioactivity.

We are interested in the mechanisms by which endocrine and developmental factors regulate TSH synthesis at both pre-translational and post-translational levels. Thyroid hormone profoundly decreases transcription of the TSH beta gene, while TRH and agents modifying cyclic AMP increase transcription. To elucidate the molecular mechanisms underlying these effects, human embryonal kidney cells were transfected with constructs of the human TSH-beta gene fused to the chloramphenicol acetyl transferase gene. The first exon of human TSH-beta contains an element that increases basal expression and mediates T3-induced gene repression, probably through a direct interaction with c-erbA beta. In contrast, TRH and agents modifying cyclic AMP mediate increased transcription of TSH-beta through interacting with upstream regulatory elements. Thyroid hormone, TRH and developmental factors also regulate the branching pattern and relative sialylation of TSH carbohydrate chains, which may affect TSH action in vitro and in vivo.

Cell Line↗
PubMed1990

Psychological impact of osseointegrated dental implants.

This longitudinal study of 39 patients who underwent treatment involving osseointegrated implants examined problems in oral and psychosocial functioning, expectations and experiences of difficulties with surgery, satisfaction with surgery, body image, neuroticism, self-concept, and extroversion. Patients completed six questionnaires from before phase 1 surgery to the final recall appointment for the new prosthesis (12 to 18 months after phase 1 surgery). The most common problems reported before treatment were those associated with eating; esthetics was less of a concern. Significant improvements in all problem areas were observed immediately after phase 2 surgery. Expectations of surgery-related problems were generally consistent with experiences immediately after phase 1 surgery, but more negative than experiences following phase 2 surgery. Body image before treatment was most negative vis-à-vis teeth. Significant improvements were found not only regarding teeth, but also on facial, mouth, and even overall body image. Satisfaction scores were generally high, but showed continued improvements through the final assessment. The only group experiencing negative outcomes consisted of patients scoring high on neuroticism.

Adult↗
PubMed1989

M-VAC or MVC for the treatment of advanced transitional cell carcinoma: metastatic, induction, and adjuvant.

The cisplatin-based combination chemotherapy regimens of M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) or MVC (methotrexate, vincristine, cisplatin) were given to 25 patients with metastatic urothelial carcinoma, 13 with locally advanced bladder cancer, and 10 as adjuvant therapy after radical surgery. Toxicity was significant with two deaths. Forty-eight percent of the patients with metastatic disease had a complete (20%) or partial (28%) response. Survival was only improved if a CR was achieved. Nine of 13 patients given M-VAC/MVC as neoadjuvant therapy underwent cystectomy and six are free of disease (mean 31 months). Three of the four patients who did not have radical surgery are also free of disease. These regimens appear to be superior to cisplatin alone. In the overall response evaluation, however, toxicity is greater.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Serum erythropoietic activity in acute anemia--an animal model.

Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.

Acute Disease↗
PubMed1989

Ontogeny of thyrotropin-releasing hormone gene expression in the rat diencephalon.

The development of thyrotropin-releasing hormone (TRH) gene expression in the rat diencephalon was studied using in situ hybridization histochemistry. The first neurons expressing the TRH gene were found on gestational day 14 (E14) in the lateral hypothalamus, shortly after completion of their last cell division. On E15 and E16, additional labeled cells appeared medially in the developing dorsomedial and paraventricular nuclei, respectively, followed on E17 by cells in the preoptic area. The number of labeled cells in the hypothalamus continued to increase during the last part of gestation. At birth, TRH mRNA neurons were present in all the locations seen in the adult hypothalamus. During the first week of life, the labeling intensity and number of neurons containing TRH mRNA continued to increase at the locations described above. TRH mRNA was not detected in the reticular thalamic nucleus until the 7th postnatal day when some labeled cells appeared in its dorsocaudal portion. Over the next 10 days, the number of labeled cells and the intensity of labeling in the thalamic reticular nucleus progressively increased. During the same period of time, only small changes in the number and intensity of labeled cells in the hypothalamus were seen. On the 21st postnatal day, after a decrease in labeling in the lateral hypothalamus had been noted, final adult patterns of expression were present. With the very sensitive and anatomically specific method of in situ hybridization histochemistry, the ontogeny of TRH gene expression in the rat diencephalon has been elucidated.

Age Factors↗
PubMed1989

Pre-translational and post-translational regulation of TSH synthesis in normal and neoplastic thyrotrophs.

We are interested in the mechanisms by which endocrine and developmental factors regulate TSH synthesis at both pre-translational and post-translational levels. Thyroid hormone profoundly decreases transcription of the TSH-beta gene, while TRH and agents modifying cyclic AMP increase transcription. To elucidate the molecular mechanisms underlying these effects, human embryonal kidney cells were transfected with constructs of the human TSH-beta gene fused to the chloramphenicol acetyltransferase gene. The first exon of human TSH-beta, contains an element that increases basal expression and mediates T3-induced gene repression, probably through a direct interaction with c-erbA beta. This transcriptional repression by T3 appears aberrant in thyrotropic tumors. In contrast, TRH and agents modifying cyclic AMP mediate increased transcription of TSH-beta through interacting with upstream regulatory elements. Thyroid hormone, TRH and developmental factors also regulate the branching pattern and relative sialylation of TSH carbohydrate chains, which may affect TSH action in vitro and in vivo. Certain thyrotropic tumors produce TSH with more complex carbohydrate branching patterns, which may increase its biologic activity.

Humans↗
PubMed1989

Prolonged converting enzyme inhibition in non-modulating hypertension.

Patients with normal- or high-renin non-modulating essential hypertension fail to shift their adrenal sensitivity on a low sodium diet in response to an infusion of angiotensin II (Ang II). In a prior study, 72 hours of converting enzyme inhibition (CEI) partially corrected this subnormal aldosterone response to Ang II in patients with non-modulating hypertension. Since it was uncertain whether the failure to restore normal adrenal responsiveness reflected a continued abnormality or an insufficient duration of CEI, the present study was performed wherein subjects were studied before CEI and then 72 hours and 6 weeks after CEI. Adrenal and renovascular responses were assessed in 13 subjects with normal- or high-renin hypertension in response to an infusion of Ang II (0.3, 1.0, and 3.0 ng/kg/min) in balance on a 10 meq Na+/100 meq K+ diet. Eight of 13 had a normal plasma aldosterone increment above control levels (greater than or equal to 15 ng/dl) and were classified as modulators; the remaining subjects (five of 13) were classified as non-modulators. Enalapril was then administered for 72 hours and 6 weeks, and the assessment of the Ang II dose-response relations was repeated. In the modulators, there was no change compared with levels before CEI in the aldosterone dose-response curve or threshold sensitivity to infused Ang II at either 3 days or 6 weeks after CEI administration. In the non-modulators, CEI for 72 hours partially restored aldosterone responsiveness, but more prolonged CEI for 6 weeks completely corrected the defect, restoring aldosterone responsiveness on a sodium-restricted diet to that seen in modulators and in normotensive control subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗
PubMed1989

Altered thyrotropin (TSH) carbohydrate structures in hypothalamic hypothyroidism created by paraventricular nuclear lesions are corrected by in vivo TSH-releasing hormone administration.

TSH is a glycoprotein hormone composed of two subunits with attached carbohydrate chains that have varying structural characteristics. To determine the role of TRH in vivo in regulating structural characteristics of TSH carbohydrate chains, adult rats received paraventricular nuclear (PVN) lesions (n = 6) or sham lesions (n = 6). The PVN contain large amounts of TRH, and rats with lesions in these hypothalamic nuclei have been shown to have decreased plasma thyroid hormone levels. At 10 days after surgery, sc osmotic pumps infusing saline or 1 mg/kg/day TRH were placed. At 14 days after surgery, pituitaries were removed and incubated with [3H]glucosamine for 24 h. Glycopeptides prepared from secreted TSH were sequentially eluted from Concanavalin-A chromatography columns selecting unbound, weakly bound, and strongly bound forms. Plasma free T4 was lower in the PVN lesioned rats treated with saline than sham lesioned rats treated with saline (1.6 +/- 0.4 vs. 5.2 +/- 0.1 ng/dl, P less than 0.001). In vivo TRH administration in the PVN lesioned group normalized plasma free T4 but had no effect on free T4 in the sham group. Secreted TSH glycopeptides in the PVN lesioned rats treated with saline as compared to sham lesioned rats treated with saline had fewer unbound forms reflecting multiantennary structures (43 +/- 4 vs. 57 +/- 1%; P less than 0.05) and more weakly bound forms reflecting biantennary structures (50 +/- 4 vs. 35 +/- 2%; P less than 0.05). TRH administration in vivo normalized the Concanavalin-A binding pattern of secreted TSH glycopeptides in the PVN lesioned group but had no significant effect in the sham lesioned group. TSH alpha-subunit demonstrated both multi- and biantennary forms but TSH-beta subunit showed a predominance of multiantennary forms in both the PVN and sham lesioned groups treated with saline. In vivo changes in TRH levels altered TSH carbohydrate characteristics as described above for both subunits. In summary, hypothalamic hypothyroidism altered TSH carbohydrate structures, and in vivo TRH administration normalized these structures in parallel with the correction of serum free T4. In addition to reported quantitative changes in TSH in response to TRH, these qualitative changes may have an important effect on TSH action.

Animals↗