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Biomedical subjects

D W Warren

Publications and source records attributed to D W Warren.

At least 145 records · Page 8Linked to original sources
PubMed1984

Effects of 1,2-dibromo-3-chloropropane on male reproductive function in the rat.

The pesticide 1,2-dibromo-3-chloropropane (DBCP) is a known male reproductive toxin. Previous studies employed production-grade DBCP containing allyl chloride and epichlorohydrin, both capable of producing effects similar to DBCP. The purpose of this study was to determine if purified DBCP caused the same effects as DBCP containing allyl chloride. Rats were injected for 6 mo with varying doses of pure or production-grade DBCP. Very few differences were observed in the parameters measured between pure and production-grade DBCP-treated animals at any one dose level. Treatment with 25 mg/kg DBCP, pure or production grade, reduced body weight as well as the weight of the testes, prostate glands and seminal vesicles, and elevated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This dose of pure DBCP reduced serum testosterone. Treatment with 5 mg/kg of either grade DBCP caused decreases only in body and testis weights. Animals treated with 1 mg/kg did not show any major differences from controls. These results indicate that DBCP, and probably not a contaminant, is responsible for the effects observed on male reproduction. Furthermore, DBCP appears to affect either androgen action or production since multiple androgenic indices are affected by DBCP administration.

Animals↗
PubMed1984

Ontogeny of gonadotropin receptors in the fetal and neonatal rat testis.

To evaluate the extent to which LH receptors may participate in the regulation of testosterone production by the fetal and neonatal rat testis, the gonadal content of LH receptors was determined and correlated with the gonadal content of testosterone and other steroids at daily intervals throughout the period of sexual differentiation and early neonatal life. Also, to determine if FSH has a potential role during fetal life, FSH receptors were measured from 14.5 until 21.5 days of gestation, just before birth. LH receptors were first detected in the fetal rat testis at 15.5 days of gestation, at a concentration of 0.072 +/- 0.016 fmol/gonad. This is the time at which previous studies have shown a biological response to LH stimulation with increases in cAMP and testosterone production. LH receptor content remained constant from 15.5-17.5 days of gestation and then increased sharply at 18.5 days of gestation to 0.706 +/- 0.046 fmol/gonad, coincident with a surge in the testosterone content of the fetal testis. LH receptor content continued to rise until birth, reaching a maximum level of 2.00 +/- 0.24 fmol/gonad at 21.5 days of gestation, and did not significantly differ from this value through 5 days after birth, whereas intratesticular testosterone content decreased after birth. FSH receptors could be measured from 17.5 days of gestation, but remained very low through 19.5 days of fetal life. At 20.5 days, FSH receptor levels began to rise sharply and continued to increase through 21.5 days of gestation, just before birth. These data show that LH receptors are measurable at the time when the fetal testis becomes responsive to LH stimulation. It is possible that the increase in LH receptors may act as a mechanism for amplification of the stimulatory effect of low circulating LH levels on the fetal testis being concomitant with the intratesticular testosterone increase at the same stage. The decrease in testosterone production after birth cannot be attributed to a decrease in LH receptors in the neonatal gonad. Since 5 alpha-reduced androgens increase after birth, other possibilities, such as alternative steroid pathways, are a more likely explanation for the decrease in testosterone content. The presence of FSH receptors in the fetal testis imply that this hormone may have a function in the developing gonad, particularly in the last 2 days of fetal life.

Aging↗
PubMed1983

Delay in the age of balano-preputial skinfold cleavage and alterations in serum profiles of testosterone, 5 alpha-androstane-3 alpha,17 beta-diol, and gonadotropins in adult rats treated during puberty with luteinizing hormone releasing hormone.

Previous work has shown that chronic treatment of intact, immature male rats with luteinizing hormone releasing hormone (LHRH) decreases sex accessory gland weights and results in retardation of the normal developmental increase in the ratio of serum testosterone (T)/5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Diol) via an apparent enhancement of testicular 5 alpha-reductase or 3 alpha-hydroxysteroid oxidoreductase activities. In the present work, androgen dependent balano-preputial skinfold cleavage was significantly delayed by approximately one week in intact, immature male rats which were treated daily for two weeks with either 1.0 micrograms, 2.5 micrograms or 5.0 micrograms of LHRH during a discrete phase of pubertal development (28-41 days of age). In intact, adult (62 day old) animals which received LHRH treatments during pubertal development, serum T concentrations and sex accessory gland weights were reduced compared to control animal values. Serum 3 alpha-Diol content in the adult rats was either unaltered or increased significantly depending on the LHRH dosage employed during sexual development. Serum luteinizing hormone concentrations were not different between control and LHRH-pretreated adult rats whereas the highest dosage of LHRH employed (5.0 micrograms) during puberty resulted in a significant elevation of adult serum follicle stimulating hormone levels. It is suggested that chronic LHRH treatment of the male rat during puberty results in a perturbation in testicular androgen biosynthetic activities and an impairment of pituitary-testicular hormone feedback mechanisms which persist at least through early adulthood.

Androstane-3,17-diol↗
PubMed1983

Development of heterologous down-regulation of lactogen receptors in the rat testis.

Gonadotropin-induced loss (down-regulation) of testicular lactogen receptors was studied in 5-60-day-old rats. An i.m. injection of 600 IU/kg of hCG elicited in 5-day-old animals a 38-56% increase in testicular lactogen binding, measurable between 6 and 72 h after the hormone injection. In contrast, at the age of 60 days the same hCG dose decreased lactogen receptors by 75% at 24 h, which loss recovered in 2-3 days. When the amount of lactogen receptors was measured 24 h after the hCG injection (600 IU/kg) at different ages, the binding increased on average by 50% between ages 5 and 20 days, no effect on binding was seen at day 30, and a loss of binding by 50% was evident in animals of 40 days of age and older. The present results indicate that the plasma-membrane events elicited by gonadotropin binding to neonatal Leydig cells are clearly different from those occurring in the adult, and that down-regulation and functional coupling of LH and lactogen receptors are accompaniments of functional differentiation of the Leydig cell during pubertal maturation.

Age Factors↗
PubMed1983

Absence of gonadotropin-induced desensitization of testosterone production in the neonatal rat testis.

The formation of testosterone and some of its precursors (pregnenolone, progesterone, 17-hydroxyprogesterone and androstenedione) was studied in response to hCG stimulation in neonatal (5-day-old) and adult (60-day-old) male rats. Evidence for a biphasic testosterone response was observed at both ages, with a sharp increase within the first hours, and a secondary peak at 2-3 days after the hormone injection, when monitored by intratesticular and serum steroid measurements. The decreased testosterone production between the two peaks coincided in the adult animals with a marked increase of progesterone and 17-hydroxyprogesterone production, in keeping with the known gonadotropin-induced lesions of testicular androgen production. In contrast, no increase in C21-form testosterone precursors could be observed in the neonatal rat. When in vitro testicular production of cAMP, testosterone and progesterone was studied at the two ages 24 h after the hCG injection, a decrease in extracellular cAMP and testosterone but an increase in progesterone was observed in the adult testis. In the neonate, cAMP production was decreased, but testosterone production stayed high, and progesterone production increased only marginally. The present results indicate that the adult-type steroidogenic lesions following in vivo hCG stimulation, resulting in decreased testosterone production and accumulation of C21 steroid precursors, are not operative during the fetal-neonatal growth phase of rat testis Leydig cells.

17-alpha-Hydroxyprogesterone↗
PubMed1982

Hormonal regulation of gonadotropin receptors and steroidogenesis in cultured fetal rat tests.

Gonadotropic activation of the adult rat testis in vitro and in vivo is followed by down-regulation of luteinizing hormone receptors and decreased androgen responses to subsequent hormonal stimulation. In contrast, treatment of cultured fetal testes with gonadotropins and dibutyryl adenosine 3',5'-monophosphate enhanced steroidogenic responsiveness and did not cause the luteinizing hormone-receptor loss and desensitization that is characteristic of the adult gonad. The analysis of gonadotropin receptors and action in cultured fetal testis cells facilitates developmental studies of gonadal function, and has revealed significant differences in the responses of fetal and adult Leydig cells to gonadotropic regulation.

Animals↗
PubMed1982

Urinary immunoprecipitation method for estimation of thyroxine to triiodothyronine conversion in altered thyroid states.

A new method is described for the estimation of T4 to T3 conversion in man and is applied to the study of hyperthyroid and hypothyroid clinical states. The method employs simultaneous iv injection of [125I]T4 and [131I]T3 with isolation of the labeled T3 tracers in 4- to 8-day pooled urine samples by a combination of solvent extraction, desalting, and immunoprecipitation procedures. Using [131I]T3 as a recovery standard, the T4 to T3 conversion ratio was found to be 0.470 +/- 0.011 in euthyroid subjects. This confirmed our earlier findings of 0.482 +/- 0.014 using a paper chromatographic method and nonsimultaneous isotope administration. The conversion ratio was increased in hypothyroidism to 0.535 +/- 0.011 (P less than 0.02) and decreased in hyperthyroidism to 0.415 +/- 0.009 (P less than 0.01). These changes parallel the fraction of the radioiodine collected in the urine for both T4 and T3; normal values are 77 +/- 4% for T4 and 76 +/- 4% for T3, values in hypothyroidism are 79 +/- 1% for T4 and 79 +/- 3% for T3, and values in hyperthyroidism are 58 +/- 3% for T4 and 58 +/- 5% for T3 (P less than 0.01). These findings indicate that 1) urinary T4 to T3 conversion values are highly reproducible in euthyroid as well as hyperthyroid and hypothyroid states; 2) the reduction in T4 to T3 conversion in hyperthyroidism probably reflects increased T4 disposal by nondeiodinative pathways and possibly the reverse in hypothyroid states; and 3) since urinary T4 to T3 conversion values in euthyroid subjects exceeded all reported conversion values in blood, there may be an alternate pathway of T3 production and disposal which is not reflected in the blood T3 production rate.

Adult↗
PubMed1981

Quantitative evaluation of nasal airflow in relation to facial morphology.

This study examines the relationship between facial morphology and nasal respiration. Nasal resistance to expiratory airflow, average volume flow rate, and temporal characteristics of the respiratory cycle were measured for twenty-eight adults. Subjects were categorized as having (1) normal facial proportions with competent lips (n = 10), (2) normal facial proportions with incompetent lips (n = 9), and (3) long vertical face height (n = 9). Results indicate that the three groups do not differ significantly in terms of nasal airflow. Lip incompetence is not synonymous with mouth breathing. Although long-faced subjects as a group had a higher mean value of nasal resistance, the range of variation was so great as to preclude the diagnosis of nasal obstruction from an assessment of facial morphology.

Adolescent↗
PubMed1981

A new method for measurement of the conversion ratio of thyroxine to triiodothyronine in euthyroid man.

A new method for the measurement of the conversion ratio (CR) of T4 to T3 in euthyroid man is described. In contrast to previously described studies, this investigation relied on sampling of urine rather than plasma after isotopic labeling of the study subject. The CR value determined in six euthyroid men was 0.482 +/- 0.014. Thus, approximately half of the daily T4 production is converted to T3 as determined by this method. A major advantage of this technique is its reproducibility, as demonstrated by the low coefficient of variation of 6.8% in the study group, which is not significantly different from the 6.7% coefficient of variation for replicate determinations on the same sample. Thus, this method may be useful tool in comparing the CR of T4 to T3 in man under varying conditions even if only small differences in conversion efficiencies exist between groups. One apparent discrepancy observed in the present study is that the calculated T3 produced from the conversion of T4 exceeded the simultaneously calculated daily T3 production rate measured in blood. The cause of this discrepancy is presently unknown, but may represent T3 produced from T4 by renal or extrarenal sources which is excreted without contributing to the T3 blood production rate. However, the reproducibility of the method and the smaller amounts of labeled isotope required show promise that this technique may be useful in assessing T4 to T3 conversion in a variety of altered metabolic states.

Adult↗
PubMed1980

Adenoid involution and developing hypernasality in cleft palate.

Information about the adenoid mass is reviewed, and the phenomenon of gradual development of hypernasality as a result of adenoidal involution is described in two patients selected from a sample of 122 with repaired cleft palate. Three types of radiographically determined closure patterns of the velum against the adenoid pad are presented. Our clinical experience suggests that the results of aerodynamic studies, completed on a longitudinal basis, may identify patients who are at risk in maintaining normal resonance balance one year or more in advance of perceptual or radiographic evidence of velopharyngeal incompetency.

Adenoidectomy↗
PubMed1980

Effects of increased vertical dimension on size of constriction port and fricative sound intelligibility.

The effect of increased vertical bite dimension on fricative sound productions was studied in five adults who wore dentures. Oral port size and sound intelligibility were evaluated at different degrees of artificially induced open bite. The data demonstrate that rapid compensatory adjustments occurred and oral port size changed minimally at all degrees of opening tested. However, in three of the subjects, sound intelligibility declined at the 6-mm opening, and in all subjects, a four-fold increase in sound distortions occurred in the edentulous state. This finding suggests the possibility that either physiological parameters are controlled more successfully than acoustical parameters or that compensatory efforts to maintain constrictor size may, under certain circumstances, adversely affect sound intelligibility.

Adult↗
PubMed1980

Speech considerations with maxillary advancement procedures.

Advancement of the maxilla has the potential to cause hypernasal speech, especially in patients with repaired cleft palates. Findings in three patients whose speech was at risk with maxillary advancement procedures are discussed, as well as their management. Diagnostic guidelines for identifying patients whose speech may be adversely affected by maxillary advancement are also presented.

Adolescent↗