Biomedical subjects

J E Hall

Publications and source records attributed to J E Hall.

At least 145 records · Page 8Linked to original sources

PubMed1997

Comparison of the water transporting properties of MIP and AQP1.

In this paper we compare the water-transport properties of Aquaporin (AQP1), a known water channel, and those of the 28 kD Major Intrinsic Protein of Lens (MIP), a protein with an undefined physiological role. To make the comparison as direct as possible we measured functional properties in Xenopus laevis oocytes injected with cRNAs coding for the appropriate protein. We measured the osmotic permeability, Pf, (using rate of swelling) and the surface density of plasma membrane proteins (using freeze-fracture electron microscopy) in the same oocytes. Knowing both Pf and the number of exogenously expressed proteins in the membrane, we estimated the single-molecule permeability to be 2.8 x 10(-16) cm3/sec for MIP and 1.2 x 10(-14) cm3/sec for AQP1. As a negative control, a mutant MIP, truncated at the carboxyl-terminal, was shown by western blotting to be expressed, but this protein resulted in no increase in either water permeability or particle density. (Interestingly, the truncated protein was glycosylated, while the complete MIP transcript was not.) Water transport by MIP had a higher activation energy (approximately 7 Kcal/ mole) than water transport by AQP1 (approximately 2.5 Kcal/Mole) but a substantially lower activation energy than water flux across bare oolemma (approximately 20 Kcal/mole). Though the water-transport properties of MIP and AQP1 differ quantitatively, they are qualitatively quite similar. We conclude that MIP, like AQP1, forms water channels when expressed in oocytes. Thus water transport in the lens seems a plausible physiological role for MIP.

Animals↗

PubMed1997

Functional analysis of nodulin 26, an aquaporin in soybean root nodule symbiosomes.

Upon infection of soybean roots, nitrogen-fixing bacteria become enclosed in a specific organelle known as the symbiosome. The symbiosome membrane (SM) is a selectively permeable barrier that controls metabolite flux between the plant cytosol and the symbiotic bacterium inside. Nodulin 26 (NOD 26), a member of the aquaporin (AQP) water channel family, is a major protein component of the SM. Expression of NOD 26 in Xenopus oocytes gave a mercury-sensitive increase in osmotic water permeability (Pf). To define the biophysical properties of NOD 26 water channels in their native membranes, symbiosomes were isolated from soybean root nodules and the SM separated as vesicles from the bacteria. Permeabilities were measured using stopped-flow fluorimetry in SM vesicles with entrapped carboxyfluorescein. Osmotic water permeability (Pf) of SM was high, with a value of 0.05 +/- 0.003 cm/s observed at 20 degrees C (mean +/- S.E.; n = 15). Water flow exhibited a low activation energy, was inhibited by HgCl2 (0.1 mM), and exhibited a unit conductance of 3.2 +/- 1.3 x 10(-15) cm3/s, a value 30-fold lower than that of AQP 1, the red blood cell water channel. Diffusive water permeability (Pd) was 0.0024 +/- 0.0002 cm/s, and the resulting Pf to Pd ratio was 18.3, indicating that water crosses the SM in single file fashion via the NOD 26 water channel. In addition to high water permeability, SM vesicles also show high mercury-sensitive permeability to glycerol and formamide, but not urea, suggesting that NOD 26 also fluxes these solutes. Overall, we conclude that NOD 26 acts as a water channel with a single channel conductance that is 30-fold lower than AQP 1. Because the solutes that permeate NOD 26 are far larger than water, and water appears to cross the channel via a single file pathway, solute flux across NOD 26 appears to occur by a pathway that is distinct from that for water.

Animals↗

PubMed1997

High-performance liquid chromatographic assay detects pentamidine metabolism by Fisher rat liver microsomes.

Fisher rat liver microsomes metabolized the antimicrobial drug pentamidine to four new compounds detected by gradient elution reversed-phase high-performance liquid chromatography with variable wavelength detection. Coelution experiments with pentamidine metabolite standards determined the new peaks to be previously identified hydroxylated metabolites of pentamidine, with 1,5-bis(4'-amidinophenoxy)-3-pentanol and 1,5-di-(4'-amidinophenoxy)-2-pentanol formed in the greatest amount. The data contradict a previous report that Fisher rat liver homogenates do not metabolize pentamidine. Pentamidine and its known primary metabolites have almost identical absorption spectra; thus, pentamidine metabolism must be evaluated using gradient elution HPLC to resolve pentamidine from its metabolites. The current assay has now been used to demonstrate that Fisher and Sprague-Dawley rat, mouse, rabbit and human liver microsomes all metabolize pentamidine in vitro.

Animals↗

PubMed1997

Purification, visualization, and biophysical characterization of Kv1.3 tetramers.

The voltage-gated K+ channel of T-lymphocytes, Kv1.3, was heterologously expressed in African Green Monkey kidney cells (CV-1) using a vaccinia virus/T7 hybrid expression system; each infected cell exhibited 10(4) to 5 x 10(5) functional channels on the cell surface. The protein, solubilized with detergent (3-[cholamidopropyl)dimethylammonio]-1-propanesulfonic acid or cholate), was purified to near-homogeneity by a single nickel-chelate chromatography step. The Kv1.3 protein expressed in vaccinia virus-infected cells and its purified counterpart are both modified by a approximately 2-kDa core-sugar moiety, most likely at a conserved N-glycosylation site in the external S1-S2 loop; absence of the sugar does not alter the biophysical properties of the channel nor does it affect expression levels. Purified Kv1.3 has an estimated size of approximately 64 kDa in denaturing SDS-polyacrylamide electrophoresis gels, consistent with its predicted size based on the amino acid sequence. By sucrose gradient sedimentation, purified Kv1.3 is seen primarily as a single peak with an approximate mass of 270 kDa, compatible with its being a homotetrameric complex of the approximately 64-kDa subunits. When reconstituted in the presence of lipid and visualized by negative-staining electron microscopy, the purified Kv1.3 protein forms small crystalline domains consisting of tetramers with dimensions of approximately 65 x 65 A. The center of each tetramer contains a stained depression which may represent the ion conduction pathway. Functional reconstitution of the Kv1.3 protein into lipid bilayers produces voltage-dependent K+-selective currents that can be blocked by two high affinity peptide antagonists of Kv1.3, margatoxin and stichodactylatoxin.

Animals↗

PubMed1997

Theoretical analysis of the mechanisms of chronic hyperinsulinemia.

Steady-state insulin resistance results in a fasting hyperinsulinemia and is a common feature of type II diabetes mellitus and obesity. In this study, a systems analysis approach was used to study glucose homeostasis which is considered as the dynamic balance between glucose release by the liver and its uptake by the peripheral tissues as regulated by insulin and glucagon. A series of computer simulation studies were performed utilizing a mathematical model of glucose homeostasis. The purpose of the study was to better understand the factors which control glucose balance and to ascertain their relative importance in the development of steady state, fasting hyperinsulinemia. When peripheral cellular insulin receptors which regulate glucose uptake were reduced to 25% of normal, the steady state plasma insulin concentration showed little change from the basal level of 8 microU/ml. When insulin receptors in the liver were also reduced to 25% of normal, the steady state insulin concentration increased from the basal levels to 32 microU/ml. Reducing pancreatic alpha cell insulin receptors to 25% of normal further increased the hyperinsulinemia to 80 microU/ml. Hence, this study suggests that the liver and its release of glucose, as controlled by insulin and glucagon, plays a central role in the development of a steady-state insulin resistance and hyperinsulinemia.

Adult↗

PubMed1997

Exogenous gonadotropin stimulation is associated with increases in serum androgen levels in in-vitro fertilization-embryo transfer cycles.

OBJECTIVE: To examine serum androgen profiles in women undergoing ovarian stimulation with exogenous gonadotropins in the setting of IVF-ET. DESIGN: Prospective study. SETTING: University hospital IVF-ET program. PATIENT(S): Seventeen ovulatory women undergoing IVF-ET for endometriosis, male factor infertility, or tubal disease. INTERVENTION(S): A standard long protocol of GnRH agonist (GnRH-a) pretreatment (1 mg of leuprolide acetate SC for 10 days) was administered before ovulation induction with a urinary gonadotropin preparation. MAIN OUTCOME MEASURE(S): After 10 days of GnRH-a treatment and on the day of hCG administration, serum concentrations of LH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS; the free androgen index (T/SHBG); and the number of follicles, oocytes, and embryos were assessed. RESULT(S): Serum samples after 10 days of GnRH-a treatment showed incomplete LH suppression. While continuing the agonist during ovarian stimulation, LH values were suppressed further. However, serum T and A concentrations and the free androgen index showed a significant increase (samples drawn just before hCG administration). Serum T levels after 10 days of GnRH-a (before the administration of exogenous gonadotropins) were correlated negatively with the subsequent number of embryos. CONCLUSION(S): Serum LH suppression with a conventional regimen of GnRH-a is incomplete in this heterogeneous group of ovulatory women. Exogenous gonadotropin stimulation results in a marked increase in ovarian androgen secretion.

Adult↗

PubMed1997

The origin of endothelin-1 in patients with severe preeclampsia.

OBJECTIVE: To determine the site of origin of increased concentrations of plasma endothelin-1 in patients with severe preeclampsia. METHODS: Twelve patients with severe preeclampsia undergoing an indicated abdominal delivery had endothelin-1 levels measured from plasma specimens drawn from right and left uterine and antecubital veins before delivery and after placenta removal with uterine curettage. Twelve uncomplicated control patients undergoing abdominal delivery had endothelin-1 concentrations drawn by an identical protocol. Clinical staff members were blinded to endothelin-1 results and laboratory staff were blinded to patient group assignment and sample source. Endothelin-1 plasma concentrations were determined by radioimmunoassay and data were analyzed by paired t test. RESULTS: No difference in endothelin-1 concentration was noted with respect to placental location, central versus peripheral, or predelivery versus postdelivery sampling procedures. Overall, patients with preeclampsia had higher plasma concentrations of endothelin-1 (mean 11.0 +/- 6.6 pg/mL) compared with normotensive patients (mean 8.4 +/- 6.7 pg/mL, P < .005). CONCLUSION: The decidual-placental interface does not appear to be the source of increased plasma endothelin-1 concentrations found in severe preeclampsia. The origin of this increase remains uncertain.

Adult↗

PubMed1997

Inhibition of thromboxane synthesis attenuates insulin hypertension in rats.

Chronic insulin infusion in rats increases mean arterial pressure (MAP) and reduces glomerular filtration rate (GFR), but the mechanisms for these actions are not known. This study tested whether thromboxane synthesis inhibition (TSI) would attenuate the renal and blood pressure responses to sustained hyperinsulinemia. Male Sprague-Dawley rats were instrumented with arterial and venous catheters, and MAP was measured 24 h/day. After 4 days of baseline measurements, endogenous synthesis of thromboxane was suppressed in 7 rats by infusing the thromboxane synthetase inhibitor, U63557A, intravenously (30 microg/kg/min) for the remainder of the experiment; 7 other rats received vehicle. Baseline MAP was not significantly different between vehicle and TSI rats (96 +/- 1 v 99 +/- 1 mm Hg). After 3 days of U63557A or vehicle, a 5-day control period was started, followed by a 7-day infusion of insulin (1.5 mU/kg/min, intravenously). Glucose (22 mg/kg/min, intravenously) was infused along with insulin to prevent hypoglycemia. In the control period, MAP was not different between vehicle and TSI rats (99 +/- 2 v 100 +/- 1 mm Hg), but MAP increased throughout the 7-day infusion period only in the vehicle rats with an average increase in blood pressure of 7 +/- 2 mm Hg. In the control period, GFR was lower in vehicle rats compared with TSI rats (2.5 +/- 0.1 v 3.1 +/- 0.2 mL/min, P = .06), and the decrease to 81% +/- 4% and 91% +/- 6% of control, respectively, during insulin was significant only in the vehicle rats. All variables returned toward control during a 6-day recovery period. These results suggest that full expression of hypertension and renal vasoconstriction during hyperinsulinemia in rats is dependent on a normal ability to synthesize thromboxane.

Animals↗

PubMed1997

Blood loss during first trimester termination of pregnancy: comparison of two anaesthetic techniques.

We have compared the effects of two anaesthetic techniques on blood loss during suction termination of pregnancy. Forty-eight ASA grade I-II patients were allocated randomly to one of two groups: group 1 received propofol induction followed by a standard propofol infusion; group 2 received propofol induction followed by maintenance with 1% isoflurane. Both groups received bolus doses of either propofol (group 1) or isoflurane (group 2) if anaesthesia was too light. All patients were given fentanyl 1 micrograms kg-1 on induction. The products of conception were evacuated into a closed suction bottle. The products were diluted with 500 ml of heparinized saline, filtered and left for 20 min. Estimation of blood loss was performed by atomic absorption spectrometry. Mean blood losses were 40.4 ml for the isoflurane group and 18.8 ml for the propofol group. This difference was statistically significant (P = 0.0011), although actual volumes of blood loss were small and not clinically significant.

Abortion, Induced↗

PubMed1997

Comparison between halothane and sevoflurane for adult vital capacity induction.

We have examined the differences in ventilatory characteristics between halothane and sevoflurane when used for adult vital capacity induction of anaesthesia. The study was conducted in a randomized, double-blind manner. After 13 patients had been enrolled, the study was curtailed because the blinded observer thought that there was an unacceptably high incidence of adverse events. After the randomization code was revealed, the adverse events were found to be in the halothane group. Although the sample size was small, minute volumes appeared to be maintained in the sevoflurane group. Ventilatory frequencies were similar in the two groups after insertion of the laryngeal mask airway, but tidal volumes were significantly greater in the sevoflurane group (P = 0.0013).

Adolescent↗

PubMed1997

Environmental monitoring during gaseous induction with sevoflurane.

Recent research has shown that gaseous induction in adults with sevoflurane is an acceptable technique. This study was undertaken to assess if gaseous induction using sevoflurane carried in both oxygen alone, and in nitrous oxide and oxygen combined, would provide acceptable pollution levels. As an occupational exposure standard has not been set for sevoflurane, we used the target level of 20 ppm set by the manufacturer. Environmental monitoring was carried out in the anaesthetic room during eight lists where consecutive triple vital capacity sevoflurane inductions were performed. Time-weighted averages for both gases over the duration of the lists were well below the occupational exposure standards (mean 1.1 (range 0.6-1.7) for sevoflurane and 17.3 (12-23) for nitrous oxide). There were high peak concentrations during the induction process (8.3 (4.1-17) for sevoflurane and 172.4 (65-310) for nitrous oxide) although these decreased to low concentrations between anaesthetic inductions. Personal sampling was carried out from the anaesthetist's breathing zone and concentrations were also low (1.2 (0.8-2.1) for sevoflurane and 45.9 (10.1-261.6) for nitrous oxide.

Adult↗

PubMed1997

Hypertension-related morbidity and mortality in the southeastern United States.

Stroke mortality is higher in the Southeast compared with other regions of the United States. The prevalence of hypertension is also higher (black men = 35%, black women = 37.7%, white men = 26.5%, white women = 21.5%), and the proportion of patients whose hypertension is being controlled is poor, especially in white and black men. The prevalence of hypertension-related complications other than stroke is also higher in the Southeast. The five states with the highest death rates for congestive heart failure are all in the southern region. Of the 15 states with the highest rates of end-stage renal disease, 10 are in the Southeast. Obesity is very prevalent (24% to 28%) in the Southeast. Although Michigan tops the ranking for all states, 6 of the top 15 states are in the Southeast, as are 7 of the 10 states with the highest reported prevalence regarding no leisure-time physical activity. Similar to other areas of the United States, dietary sodium and saturated fat intake are high in the Southeast; dietary potassium intake appears to be relatively low. Other factors that may be associated with the high prevalence, poor control, and excess morbidity and mortality of hypertension-related complications in the Southeast include misperceptions of the seriousness of the problem, the severity of the hypertension, lack of adequate follow-up, reduced access to health care, the cost of treatment, and possibly, low birth weights. The Consortium of Southeastern Hypertension Control (COSEHC) is a nonprofit organization created in 1992 in response to a compelling need to improve the disproportionate hypertension-related morbidity and mortality throughout this region. The purpose of this position paper is to summarize the data that document the problem, the consequences, and possible causative factors.

Adult↗

PubMed1997

Single-breath inhalation induction of sevoflurane anaesthesia with and without nitrous oxide: a feasibility study in adults and comparison with an intravenous bolus of propofol.

The induction characteristics of sevoflurane in nitrous oxide and oxygen were compared with sevoflurane in oxygen alone and a propofol infusion. A vital capacity technique was used for the gaseous induction groups using a Mapleson A system and a 4-litre reservoir bag. Four end-points of anaesthesia were recorded: time to cessation of finger tapping, time to loss of eyelash reflex, time to jaw relaxation and time to regular settled breathing after laryngeal mask airway insertion. We also recorded sequential blood pressure and pulse rate, the incidence of adverse airway events and the acceptability of the induction technique. Propofol had a faster time to cessation of finger tapping (p < 0.05) and jaw relaxation (p < 0.01). These differences disappeared with the final induction stage and sevoflurane in nitrous oxide and oxygen had the faster time to regular settled breathing, though this did not reach statistical significance. Cardiovascular stability was good and comparable in all groups. There were few adverse airway events in any group and none caused oxygen saturation to fall below 96%. There was more excitation in the gaseous induction groups, though this did not interfere with induction. Patient satisfaction with induction was high.

Adolescent↗

PubMed1997

Thromboxane is required for full expression of angiotensin hypertension in rats.

Recent studies suggest that thromboxane (TX) mediates a significant component of angiotensin II (ANG II)-induced hypertension. However, there is little information to support the hypothesis that this relationship is important during chronic, physiological increases in ANG II, particularly while controlling for variation in endogenous ANG II levels induced by TX inhibition. This study tested that hypothesis in 27 chronically instrumented rats. After baseline measurements, suppression of endogenous TX was induced and maintained throughout the study in 13 rats by i.v. infusion of the TX synthesis inhibitor (TSI) U63557A: the other 14 rats received vehicle. Baseline mean arterial pressure (MAP) was not different between groups and was unchanged by TSI or vehicle. Continuous inhibition of ANG II production was then initiated in both groups of rats by i.v. infusion of the angiotensin-converting enzyme inhibitor (ACEI) benazepril. ACEI reduced blood pressure similarly in vehicle and TSI rats, from 105 +/- 2 to 91 +/- 2 mm Hg and 103 +/- 1 to 89 +/- 1 mm Hg, respectively. ANG II was then infused at 5 ng.kg-1.min-1 i.v. for 7 days in six rats from each group to restore ANG II activity to baseline levels. This dose increased MAP to 103 +/- 2 and 101 +/- 1 mm Hg in vehicle and TSI rats, respectively, values not different from pre-ACEI levels. Seven TSI rats and eight vehicle rats received a higher dose of ANG II (20 ng.kg-1.min-1 i.v.). After 7 days, MAP was higher in vehicle than in TSI rats (143 +/- 5 versus 120 +/- 4 mm Hg). These results suggest that endogenous TX is an important determinant of MAP in ANG II hypertension but may have a diminished role in blood pressure regulation when ANG II is at normal and subnormal levels.

Angiotensin II↗

PubMed1997

Insulin-induced hypertension in rats depends on an intact renin-angiotensin system.

This study tested the dependence of insulin-induced hypertension in rats on a functional renin-angiotensin system. Rats were instrumented with chronic artery and vein catheters and housed in metabolic cages. After acclimation, 10 rats began receiving the angiotensin-converting enzyme inhibitor (ACEI) benazepril at 1.8 mg.kg-1.d-1 via a continuous intravenous infusion that was maintained throughout the study; 8 control rats received vehicle. Four days after starting ACEI or vehicle, all rats entered a 5-day control period that was followed by a 7-day insulin infusion at 1.5 mU.kg-1.min-1. Glucose was coinfused at 22 mg.kg-1.min-1 to prevent hypoglycemia. Insulin infusion in control rats increased mean arterial pressure (MAP; measured 24 h/d) from an average of 101 +/- 1 to 113 +/- 2 mm Hg on day 1; MAP averaged 110 +/- 1 mm Hg for the 7-day infusion period. Glomerular filtration rate decreased, although not significantly, from 2.7 +/- 0.1 to 2.1 +/- 0.2 mL/min on day 3. Chronic ACEI decreased baseline MAP from an average of 97 +/- 1 to 79 +/- 1 mm Hg and markedly attenuated the increase in MAP during insulin. MAP averaged 81 +/- 1 mm Hg for the 7-day period and increased significantly, to 85 +/- 2 mm Hg, only on day 3. Likewise, the tendency for glomerular filtration rate to decrease was blunted. These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis.

Angiotensin II↗

PubMed1997

Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome.

UNLABELLED: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder of reproductive age women characterized in its broadest definition by the presence of oligoamenorrhea and hyperandrogenism and the absence of other disorders. Defects of gonadotropin secretion, including an elevated LH level, elevated LH to FSH ratio, and an increased frequency and amplitude of LH pulsations have been described, but the prevalence of these defects in a large, unbiased population of PCOS patients has not been determined. Sixty-one women with PCOS defined by oligomenorrhea and hyperandrogenism and 24 normal women in the early follicular phase had LH samples obtained every 10 min for 8-12 h. Pool LH levels from the frequent sampling studies were within the normal range in the 9 PCOS patients (14.8%) who were studied within 21 days after a documented spontaneous ovulation. Excluding these post-ovulatory patients, 75.0% of the PCOS patients had an elevated pool LH level (above the 95th percentile of the normal controls), and 94% had an elevated LH to FSH ratio. In the anovulatory PCOS patients, pool LH correlated positively with 17-OH progesterone (R = 0.30, P = 0.03), but not with estradiol, estrone, testosterone, androstenedione, or DHEA-S. Pool LH and LH to FSH ratio correlated positively with LH pulse frequency (R = 0.40, P = 0.004 for pool LH, and R = 0.39; P = 0.005 for LH/FSH). There was also a strong negative correlation between pool LH and body mass index (BMI) (R = -0.59, P < 10(-5)). The relationship between BMI and LH secretion in the PCOS patients appeared to be strongest with body fatness, as pool LH was correlated inversely with percent body fat, whether measured by skinfolds (R = -0.61, P < 10(-5)), bioimpedance (R = -0.55, P < 10(-4)), or dual energy x-ray absorptiometry (DEXA) (R = -0.70, P = 0.001; n = 18 for DEXA only). By DEXA, the only body region that was highly correlated with pool LH was the trunk (R = -0.71, P = 0.001). The relationship between body fatness and LH secretion occurred via a decrease in LH pulse amplitude (R = -0.63, P < 10(-5) for BMI; R = -0.58, P < 10(-4) for bioimpedance; and R = -0.64, P = 0.004 for whole body DEXA), with no significant change in pulse frequency with increasing obesity (R = -0.17, P = 0.23 for BMI). IN CONCLUSION: 1) the prevalence of gonadotropin abnormalities is very high in women with PCOS selected on purely clinical grounds, but is modified by recent spontaneous ovulation; 2) the positive relationship between LH pulse frequency and both pool LH and LH to FSH ratio supports the hypothesis that a rapid frequency of GnRH secretion may play a key etiologic role in the gonadotropin defect in PCOS patients; 3) pool LH and LH pulse amplitude are inversely related to body mass index and percent body fat in a continuous fashion; and 4) the occurrence of a continuous spectrum of gonadotropin abnormalities varying with body fat suggests that nonobese and obese patients with PCOS do not represent distinct pathophysiologic subsets of this disorder.

Adolescent↗

PubMed1997

Frequency modulation of follicle-stimulating hormone (FSH) during the luteal-follicular transition: evidence for FSH control of inhibin B in normal women.

To isolate the impact of GnRH pulse frequency on FSH secretion and to examine the effect of differing levels of FSH on inhibin B secretion during the luteal-follicular transition, exogenous GnRH was administered to GnRH-deficient women using one of two regimens, and the results were compared to those in normal women. In the GnRH-deficient women, the GnRH pulse frequency was increased from every 4 h in the late luteal phase to every 90 min on the day of menses to mimic normal cycling women (physiological frequency transition; n = 8 studies) or the GnRH pulse frequency was kept constant at a late luteal phase frequency of every 4 h through the first 6 days of the subsequent early follicular phase of cycle 2 (slow frequency transition; n = 6 studies). The differential rise in FSH secretion induced in these studies allowed us to examine the subsequent contribution of varying levels of FSH to inhibin B secretion. A physiological regimen of GnRH during the luteal-follicular transition resulted in a rise in FSH and inhibin B levels that did not differ from that in normal cycling women and a normal follicular phase length. On the other hand, maintaining a luteal frequency of GnRH for 6 days into the subsequent early follicular phase produced FSH levels significantly lower than those in the physiological transition (P < 0.05), with the greatest difference seen on the day after menses (9.1 +/- 1.0 vs. 16.4 +/- 1.4 IU/L for the slow and physiological transition groups, respectively; P < 0.005), but no difference in LH. This slower rise of FSH secretion in the slow frequency group was associated with significantly lower inhibin B levels (43.3 +/- 21.5 vs. 140.0 +/- 24.4 pg/mL, mean days 1, 3, and 5; P < 0.02), a later doubling of estradiol from baseline (day 9.6 +/- 0.9 vs. day 5.6 +/- 0.1; P < 0.02), and a longer follicular phase length (16.0 +/- 1.4 vs. 11.6 +/- 0.9 days; P < 0.05) compared with those in the physiological transition group. In conclusion, during the luteal-follicular transition, the GnRH pulse frequency contributes to but is not solely responsible for the FSH rise that initiates folliculogenesis. Alteration of FSH dynamics induced by changes in GnRH pulse frequency in GnRH-deficient women provides evidence that FSH stimulates inhibin B production in the human. Timely follicular development indicated by both estradiol and inhibin B secretion appears to be dependent on the pattern of increase in FSH during the luteal-follicular transition.

Adolescent↗

PubMed1997

Mechanisms of abnormal renal sodium handling in obesity hypertension.

Obesity-induced hypertension, like all forms of experimental and human hypertension studied thus far, is associated with renal dysfunction characterized by the resetting of pressure natriuresis. In obese subjects, this resetting is primarily a result of increased renal tubular reabsorption as glomerular filtration rate and renal blood flow are markedly elevated. Obesity activates the sympathetic nervous and renin-angiotensin systems, and causes insulin resistance and hyperinsulinemia, all of which have been postulated to increase tubular reabsorption and raise blood pressure. In humans and dogs, chronic hyperinsulinemia, comparable to that found in obesity, does not cause hypertension even in the presence of insulin resistance. Activation of the sympathetic nervous system appears to be important in obesity, as chronic adrenergic blockade or renal denervation greatly ameliorates the hypertension associated with weight gain. Resetting of pressure natriuresis in obesity may also be attributable to altered intrarenal forces caused by histologic changes in the renal medulla that may compress the loops of Henle and vasa recta, increase tubular sodium reabsorption, and activate the renin-angiotensin system. The quantitative importance of these intrarenal changes and their interrelationship with neurohumoral activation in obesity is an important area for further investigation.

Animals↗