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Biomedical subjects

T J Collins

Publications and source records attributed to T J Collins.

At least 91 records · Page 5Linked to original sources

Laser angioplasty in coronary artery disease.

At the present time all laser coronary angioplasty systems in use are investigational devices awaiting FDA approval. Preliminary results in human trials of several coronary laser angioplasty systems have been reported and appear encouraging. The technological achievement of delivering laser energy to the coronary circulation and opening occluded arteries has been accomplished. The much more difficult question of determining which patients, if any, should be offered this very expensive technology remains to be answered.

Coronary Disease↗

Repeat balloon aortic valvuloplasty for aortic valve restenosis.

Effective balloon aortic valvuloplasty (BAV) is limited restenosis. After aortic valve restenosis six patients underwent repeat BAV. In spite of the use of larger balloons there was a trend toward a less satisfactory result after repeat BAV (0.98 +/- .26 cm2 vs. 1.2 +/- .26 cm2), which did not reach statistical significance, P = .14. Mortality of the patients at 6 months was 50%. Repeat BAV may be less efficacious than the original procedure.

Aged↗

Infertility in transgenic female mice with human growth hormone expression: evidence for luteal failure.

Introduction of the human growth hormone (hGH) gene fused with mouse metallothionein I promoter into domestic mice leads to ectopic synthesis of hGH, marked stimulation of somatic growth, and female sterility. Transgenic females (produced by mating transgenic males to normal females) mated but failed to become pregnant or pseudopregnant as evidenced by the recurrence of vaginal plugs every 5-7 days. Daily injections of 1 mg progesterone, starting on day 1 postcoitum (p.c.), maintained pregnancy, suggesting that the sterility of these animals is due to inadequate luteal function. In ovariectomized female transgenic mice, median eminence (ME) turnover of dopamine (DA) was increased, and plasma prolactin (PRL) levels were reduced, presumably because of the known lactogenic activity of hGH in rodents. From these observations we suspected that either 1) the corpora lutea of these animals are unresponsive to lactogenic hormones, or 2) hGH by stimulating tuberoinfundibular dopaminergic (TIDA) neurons interferes with the increase in PRL release that normally follows mating and this, in turn, leads to luteal failure. To distinguish between these possibilities, transgenic females were treated with PRL-secreting ectopic pituitary transplants from normal females of the same strain on day 1 p.c. Eight of ten treated females became pregnant and delivered litters. We conclude that infertility of transgenic female mice with hGH expression is due to activation of the TIDA system, suppression of endogenous PRL release, and luteal deficiency.

Animals↗

Lithium: evidence for reduction in circulating testosterone levels in mice following chronic administration.

Lithium, the widely-used antipsychotic drug, is known to exert adverse effects on a number of endocrine organs. In the present investigations, the effects of chronic lithium administration on circulating levels of testosterone and plasma and pituitary levels of luteinizing hormone (LH) were evaluated in order to examine whether or not the pituitary-gonadal axis is a probable target of lithium action. Adult male C57BL/6 mice, maintained on a fixed photoperiodism (LD 14:10), were administered lithium orally, by being fed on a specially prepared chow containing 0.4% lithium chloride for 15 or 30 days, while their matched controls were maintained on standard laboratory chow. At the termination of the respective experimental schedules, the animals were decapitated, their blood collected, and plasma was separated and stored frozen. Pituitaries were quickly removed, weighed, homogenized, centrifuged and their supernatants were stored frozen. Testosterone in plasma and LH in pituitary and plasma were quantitated by standard RIA methods. Plasma Li concentration was determined by using flame photometric methods. A significant suppression in testosterone levels was noted after both 15 (p less than .01) and 30 (p less than .05) days of lithium treatment, but both pituitary and plasma LH levels remained unchanged at both the periods. It is, therefore, suggested that lithium exerts its effect directly at the level of the Leydig cells rather than through the pituitary-gonadal axis. Since the noted lithium-induced reduction of testosterone was manifested when the plasma lithium levels were within (or around) the therapeutic range, these results may have important clinical implications.

Animals↗

Paternal age and its effects on reproduction in C57BL/6NNia mice.

The reproductive capabilities of 6- and 24-month-old C57BL/6NNia male mice were compared after being paired for one month with a 4-month-old proven-fertile female. All of the younger males mated, with 96% yielding a litter; only 42% of aged males mated, with 65% siring young. There were no statistical differences in the litter sizes, nor any congenital defects noted in offspring from either age group. There was no evidence of aneuploidy in 10-day-old embryos sired from males of either age group. Aged males that failed to mate had lower body weight, a lower hematocrit, hypertrophied adrenal glands and seminal vesicles, decreased fructose levels in seminal vesicle fluid, atrophied testes with fewer sperm that were less motile, lower testosterone levels, and a greater percentage of degenerating epithelium lining seminiferous tubules. The latter group of aged mice, while appearing and acting as vigorous as aged mice that had mated, may have been experiencing disease processes associated with aging which subsequently impaired reproduction.

Adolescent↗

Somatostatin inhibits VIP-stimulated amylase release from perifused guinea pig pancreatic acini.

We have examined the direct effect of somatostatin (SRIF) on basal and stimulated amylase release from guinea pig pancreatic acini using the in vitro method of continuous perifusion. The optimal conditions of flow rate, chamber size, acinar cell volume per chamber, and period of secretagogue infusion were defined for the perifusion system. The kinetic profile of amylase release in response to cholecystokinin-octapeptide (CCK-8), vasoactive intestinal peptide (VIP), and SRIF was studied. Under optimal conditions, the acini were found to remain equally responsive to an ED50 dose of CCK-8 (0.5-0.8 nM) for 12 h of perifusion. The duration of amylase response to any given dose of CCK-8, given for the optimal period of 5 min, was 80-100 min. The total amylase released minus the basal release divided by 90 min (delta response) in response to the maximum effective (Maxeff) dose of CCK-8 (100 nM) was 14,667 +/- 1,433 U/l (amounting to a 10-fold increase compared with basal values). When compared with the amount of total delta amylase released in response to the Maxeff dose of CCK, the total amylase released in response to the Maxeff doses of SRIF (1 microM) and VIP (10 nM) was 10-21% and 51-59%, respectively. SRIF (100 nM) significantly decreased VIP- (0.1-1.0 nM) stimulated amylase release by 45-70% in the perifusion method of study but had no significant effect on the CCK-stimulated amylase release. This suggests that the perifusion method can be used for investigating the mechanism of SRIF-mediated inhibition of VIP effects on amylase release in an in vitro system.

Amylases↗

Directional instability of rear caster wheelchairs.

Although less common than conventional front caster wheelchairs, rear caster wheelchairs are still in use for several reasons. Many people find manual rear caster wheelchairs easier to maneuver indoors at slow speeds. This is especially true when the user attempts to maneuver the wheelchair very close to an object, such as a table. Electric wheelchairs often have rear casters to accommodate for front wheel drive. If the larger drive wheels are located at the front of the wheelchair, obstacles such as a curb can be negotiated much more easily. However, a major disadvantage of rear caster wheelchairs is that they are generally known to be directionally unstable, especially at high forward speeds. This paper presents the results of a study to determine specific measures that can be employed to improve the stability of this type of wheelchair. The instability of rear caster wheelchairs is due primarily to road forces that act on the tires when the wheelchair is displaced from its line of motion by a bump or other irregularity in the road surface. The paper discusses the experimental investigation of these road forces as well as a dynamic model used to study the instability problem. The results of a computer simulation program used to perform a parametric study of different design variables are discussed. Center of gravity position, caster trail distance, and caster pin friction are found to have a dominant influence on rear caster wheelchair directional control. Several simple but significant design recommendations are presented.

Acceleration↗

Effects of lithium on the pituitary-gonadal axis in the rat: evidence for dose-dependent changes in plasma gonadotropin and testosterone levels.

The purpose of the present study was to examine the effects of lithium, a drug which is now used rather widely in the treatment of acute mania and the prophylaxis of manic-depressive bipolar disorders, on the pituitary-gonadal function in the laboratory rat. Sexually adult male rats, maintained under standardized laboratory conditions (LD 14: 10; lights on at 06:00 h, CST), were injected (ip) with lithium chloride both acutely for 1 day and chronically for 5 days, and by utilizing a low and high dose. For the low dose, lithium was injected twice daily (at 10:00 and 15:00 h) at 2.5 meg/Kg for 1 and 5 days, whereas in the high dose groups, also receiving lithium twice daily and at the same hours, the dosages were 5 meq/Kg for 1 day and 3.5 meq/Kg for 5 days. Animals were sacrificed 4 hours after the last lithium (or saline) injections. Plasma and pituitary levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and plasma levels of testosterone (T) were measured by radioimmunoassay (RIA). The administration of the low dose led to a significantly higher (P less than 0.001) plasma FSH, but unaltered plasma LH, levels after 5 days. In contrast, the high dose lithium led to significant suppressions of plasma LH (P less than 0.02; on day 5) and FSH (P less than 0.001; on both day 1 and 5) levels. The levels of plasma T also showed a significant reduction following the low dose (P less than 0.02; on day 5), as well as the high dose lithium treatment, as evident after both 1 (P less than 0.02) and 5 (P less than 0.02) days. Regardless of the dosage, or the duration of treatment, pituitary gonadotropin levels remained unaltered following lithium. The results of our present experiments suggest that lithium administration, either acutely or on a chronic basis, might be associated with significant adverse effects on the pituitary-testicular axis. Furthermore, since some of the hormonal changes were evident when plasma lithium concentration was within the therapeutic range, our data may have potential clinical implications.

Aggression↗

Neuroendocrine studies in hyperprolactinaemic male mice.

In several species, including man and the rat, hyperprolactinaemia is associated with suppression of gonadotrophin release and male sexual behaviour. However, in the hyperprolactinaemic male mouse, plasma LH and FSH levels and copulatory behaviour are increased rather than suppressed. In an attempt to identify mechanism(s) which may be responsible for these effects of hyperprolactinaemia in the mouse, we have examined the effects of two ectopic pituitary isografts on several indices of hypothalamic and pituitary function in adult DBA/2J males. Animals with pituitary grafts had markedly increased plasma concentrations of prolactin, LH and FSH and enlarged seminal vesicles, whereas testicular and pituitary weights were not affected. Content of LHRH receptors and activity of aromatase in the pituitary, as well as dopamine-beta-hydroxylase activity in the hypothalamus were nearly identical in pituitary-grafted and sham-operated males. Biosynthesis of dopamine and turnover of noradrenaline in the median eminence were significantly increased in grafted males. We suggest that the increase in the activity of hypothalamic noradrenergic neurones may mediate stimulatory action of hyperprolactinaemia on LH and FSH release in the mouse. Comparison of these results with those obtained previously in the rat suggests that species differences in the effects of prolactin on gonadotrophin release may be related to its divergent effects on noradrenaline turnover.

Animals↗

Acute lithium treatment suppresses the proestrous LH surge in mice: chronic lithium leads to constant diestrus.

Although the therapeutic usefulness of lithium in manic-depressive psychosis is now well-established, a number of basic and clinical studies in recent years have shown that the administration of this anti-manic drug produces a wide range of adverse endocrine and metabolic effects. The present study was undertaken in order to examine (a) what effects acute lithium administration might have on the preovulatory surge of luteinizing hormone (LH) during proestrus, and (b) whether chronic lithium administration has any adverse effect on the estrous cycle in C57BL/6 mice. Acute injections of lithium on the day of proestrus (at 10.00, 16.00 and 18.00 h; LD 14:10; lights on at 05.00 h CST) at a dosage of 5 mEq/kg b. wt. led to a significant (P less than 0.01) suppression of the LH surge that normally occurs in the evening of proestrus at 21.00 h. Chronic administration of lithium, on the other hand, resulted in a complete disruption in the regularity of the estrous cycle. This was characterized by an increasing number of mice showing a continuous diestrous vaginal smear during the first week of exposure to lithium, after which all of the lithium-treated mice completely stopped cycling and entered into constant diestrus. These results represent for the first time that lithium has significant adverse effects on the reproductive function in the female, especially in regard to the proestrous LH surge and estrous cyclicity in mice. Since these adverse effects were manifested under conditions when plasma lithium concentrations were within or around the therapeutic range, our results provide important conceptual information concerning possible adverse effects of lithium on the reproductive function in the human female.

Animals↗

Hormonal regulation of testicular human chorionic gonadotropin binding and steroidogenesis in adult mice with different forms of hereditary diabetes and obesity.

The regulation of testicular hCG binding and steroidogenesis in adult mutant mice with hereditary diabetes and obesity was studied. Low doses of hCG caused no change in hCG binding in obese (ob/ob) mice, whereas, in diabetic (db/db) mice, the increase in binding measured 24 h after hCG administration was not as great as in normal males. Intermediate doses of hCG caused a decrease in hCG binding in obese and normal mice, but not in diabetic animals. However, 72 h after injection of intermediate doses of hCG, a decrease in hCG binding also was observed in diabetic mice. Plasma testosterone was elevated 24 h after hCG injection in all types of mice studied, but the increase in diabetic mice was smaller than in normal animals. However, 72 h after treatment with hCG, plasma testosterone was still elevated in diabetic mice, but not in normal males. In vitro, hCG stimulated testicular testosterone synthesis in all groups of mice, but the observed increase was smaller in diabetic and obese than in normal animals. Plasma LH levels were higher in diabetic than in normal mice, whereas plasma FSH and prolactin levels were lower in obese mice than in normal animals. All parameters (i.e., LH receptors and circulating hormone levels) measured in yellow (Ay/a) mice were similar to those in normal (a/a) mice. The present study indicates that in these models for noninsulin-dependent diabetes, the testicular metabolism of LH receptors and capacity to secrete steroids is altered.

Animals↗

Testicular LH receptors and circulating hormone levels in three mouse models for inherited diseases (Tfm/y, lit/lit and hyt/hyt).

In mice with testicular feminization (Tfm/y), the concentration of LH receptors (LH-R) in the testes was greatly elevated, when compared to their normal controls (Ta/y). The administration of hCG caused, 24 hours later, a much greater decrease in the number of testicular LH-R in Tfm/y than in Ta/y mice. However, whereas in Ta/y mice, the decrease in LH-R was accompanied by a greater than 20 fold increase in plasma testosterone (T) levels, the same dose of hCG failed to alter plasma T levels in Tfm/y mice. Tfm/y mice were also characterized by significantly elevated circulating LH, FSH and PRL levels. Administration of hCG decreased testicular LH-R concentration in little (lit/lit) mice, whereas it had no effect in hypothyroid (hyt/hyt) and normal mice. Treatment with hCG elevated plasma T levels in all animals, but this increase was smaller in lit/lit than in Lit/- mice, while being greater in hyt/hyt than in Hyt/- mice. The present results suggest that the Tfm locus in the mouse is involved in the regulation of testicular LH-R. The only effect of GH deficiency on the parameters studied is on hCG-stimulated testicular steroidogenesis. The lack of negative autoregulation of LH-R by hCG in hyt/hyt mice may indicate a more active testicular LH-R metabolism, perhaps as a consequence of the chronic elevation of plasma TSH levels.

Androgen-Insensitivity Syndrome↗

Water deprivation-sodium chloride intoxication in a group of feeder lambs.

Six of a group of 100 feeder lambs that had been deprived of sodium chloride, then more recently deprived of water, developed water deprivation-sodium chloride intoxication soon after water and a mineral supplement containing sodium chloride were reintroduced. The clinical signs included somnolence, intense thirst, and generalized muscle fasciculations. Serum chemical analyses revealed profound hypernatremia and hyperchloremia. Two mildly affected lambs recovered with partial water restriction and 2 severely affected lambs died despite medication to reduce cerebral edema. Postmortem examination of the 2 treated lambs and the 2 lambs found dead revealed microscopic evidence of cerebral edema and cerebrocorticonecrosis.

Animals↗

Orthotopic ovarian transplantations in young and aged C57BL/6J mice.

Orthotopic ovarian transplantations were done between young (6-wk-old) and aged (17-mo-old) C57BL/6J mice. The percentages of mice mating following surgery from the four possible ovarian transfer combinations were as follows: young into young, 83%; young into aged, 46%; aged into young, 83%; and aged into aged, 36%. The percentages of these mice that were pregnant 10 days following the presence of a vaginal sperm plug were as follows: young into young, 58%; young into aged, 9%; aged into young, 50%; and aged into aged, 0%. Some of the fetuses derived from matings of the above mice were dissociated and their cells prepared for chromosomal smears. No evidence of aneuploidy or mosaicism was found in fetuses derived from ovaries of young or aged mice. Aged ovaries, transferred to either young or aged recipients, were found to have fewer developing follicles and lower weight, which was most apparent in recipients that failed to mate or to get pregnant. Concentrations of luteinizing hormone, follicle-stimulating hormone (FSH), and prolactin in plasma from each of the pregnant recipients were analyzed by radioimmunoassay. The only statistical differences found between the transfer groups occurred in FSH concentrations. Plasma FSH was markedly elevated (P less than 0.005) in young recipients with ovaries transplanted from aged donors, in comparison to young recipients with ovaries from young donors. These data indicate that the aging ovary and uterus play a secondary role in reproductive failure and that the aging hypothalamic-hypophyseal complex is primarily responsible for the loss of fecundity in older female C57BL/6J mice.

Aging↗

Bronchiolar adenocarcinoma in a cow.

An aged beef cow had a primary lung tumor that was diagnosed postmortem. Clinical signs included inappetence, weight loss, coughing, dyspnea, and reduced lung sounds. Antibiotic treatment was ineffective. The cow was euthanatized. Postmortem examination revealed numerous, firm nodules throughout both lungs. Microscopically, the pulmonary nodules contained neoplastic cells and the diagnosis was bronchiolar adenocarcinoma. A diagnosis of pulmonary neoplasia, although rare, should be considered in an aged cow with similar historical and clinical findings.

Adenocarcinoma, Bronchiolo-Alveolar↗

Autoregulation of testicular luteinizing hormone receptors in hypogonadal (hpg/hpg) mice.

The autoregulation of testicular luteinizing hormone (LH) receptors was studied in hypogonadal (hpg/hpg) and normal mice. The basal concentration of LH receptors was more than three-fold higher in hpg/hpg than in normal mice. After injection of hCG, hpg/hpg mice showed a decrease in LH receptor levels which was not observed in normal mice. Plasma testosterone was undetectable in hpg/hpg mice, even after treatment with a single dose of hCG. Plasma prolactin levels were higher in hpg/hpg than in normal mice. The increase in basal LH receptor levels is thought to be due to a compensatory mechanism in which elevated prolactin could play a role. The differences between hpg/hpg and normal mice in the autoregulation of LH receptors observed could be due to the "hypersensitivity" of the physiologically immature testis in hpg/hpg mice to the action of hCG, to gonadotropin deficiency, particularly during the earlier stages of development, or to a direct effect of the hpg locus on the metabolism of LH receptors.

Animals↗

Orthotopic ovarian transplantation in young and aged CBA mice.

Reproductive and hormonal changes associated with CBA mice which were orthotopically transplanted with ovaries from young or aged CBA mice were studied. Reproductive decline was defined by the number of mice mating and the number of implantation sites and resorptions in pregnant mice. A high percentage of resorptions was observed in aged mice receiving ovaries from young mice. An increase in the number of resorptions and a decrease in the number of implantation sites was observed in young mice transplanted with aged ovaries. Concentrations of LH, FSH and Prl were analyzed by radioimmunoassay from plasma of pregnant and nonpregnant transplanted mice, ovariectomized and sham-operated controls. Young ovariectomized mice had elevated concentrations of LH and FSH when compared to sham-operated controls. No differences were noted between the aged ovariectomized mice although the gonadotrophin levels in these animals were higher than those in comparable young groups. The highest LH and lowest FSH concentrations were found in young to young transplanted mice. The Prl concentrations in transplanted mice did not vary between groups. These data suggest that the hypothalamic-hypophyseal complex is functioning adequately in all transplanted groups and age-related changes in the ovary and uterus are responsible for embryonic mortality.

Aging↗