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G S Jones

Publications and source records attributed to G S Jones.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and binding to beta-adrenergic receptors of p-aminobenzyl analogues of practolol and atenolol.

The p-aminobenzyl analogues (8a and 8b, respectively) of the cardioselective beta-adrenergic receptor antagonists practolol and atenolol were prepared from the corresponding phenoxymethyloxiranes in 30 and 13% yields, respectively. The dissociation constants for the beta-adrenergic receptor were measured in membrane preparations of rat heart and lung. In membranes from the heart (which contain mostly beta 1-adrenergic receptors), the affinities of the derivatives and parent compounds were similar. By contrast, in membranes from the lung (which contain mostly beta 2-adrenergic receptors), the derivatives were more potent than the parent compounds. Thus, the cardioselectivities of the p-aminobenzyl analogues 8a and 8b were about one-sixth those of the respective parents.

Adrenergic beta-Antagonists↗
PubMed1992

Aromatic trivalent arsenicals: covalent yet reversible reagents for the agonist binding site of nicotinic receptors.

The agonist binding site of nicotinic acetylcholine receptors (AChRs) includes a disulfide bond that is easily reduced with dithiothreitol to a pair of thiols, and can be then either reoxidized with dithiobis(nitrobenzoic acid) (DTNB) or irreversibly alkylated with bromoacetylcholine (BAC). Aromatic trivalent arsenicals form stable complexes with pairs of appropriately-spaced thiols, but not single thiols. Furthermore, once complexed in proteins, trivalent arsenicals can be removed with dimercaptans, such as 2,3-dimercaptopropanesulfonic acid (DMPS). In an effort to develop reagents that will covalently, yet reversibly label AChRs, we investigated the effects of two model arsenicals, p-aminophenyldichloroarsine (APA) and 4-bromoacetyl-aminophenylarsenoxide (BAPA) on two types of nicotinic receptors: AChRs from Torpedo electroplax and neuronal receptors from chick retina. APA and BAPA significantly decrease the number of 125I-alpha-bungarotoxin binding sites in reduced Torpedo AChRs. Furthermore, arsenylation of neuronal and Torpedo receptors with APA or BAPA (1) prevents reoxidation with DTNB, (2) is reversible with DMPS, and (3) protects against irreversible alkylation by BAC. In Torpedo receptors, the EC50 of protection against BAC alkylation with APA or BAPA is approximately 30 nM. APA arsenylation of Torpedo receptors persists up to 20 h, but can be reversed at any time with DMPS. These results suggest that heterobifunctional arsenicals could anchor labeling groups in the agonist binding site in order to map the agonist binding site, quantitate receptors, or purify and reconstitute functional receptors.

Acetylcholinesterase↗
PubMed1992

Effects of oxidizing and reducing analogs of acetylcholine on neuronal nicotinic receptors.

The synthesis and pharmacological characterization of dithiobisacetylcholine and dithiobis-N,N-dimethyl-4-acetylpiperazinium (two oxidizing analogs of acetylcholine), as well as those of their reduced counterparts, are described. Both the oxidizing and reducing analogs stimulate nicotinic receptors in the chick retina and block the binding of 125I-labeled neuronal bungarotoxin to retinal homogenates (IC50 values of 2 x 10(-6) to 6 x 10(-5) M). Both oxidizing compounds reverse the physiological effects of reduction by dithiothreitol on nicotinic function in intact chick retina, when applied for 2 sec (EC50 values of about 10(-5) M). This effect is selective, insofar as neither agent alters the effects of dithiothreitol treatment on receptors for N-methyl-D-aspartate. Reoxidation takes place at the disulfide located near the nicotinic receptor agonist binding site, inasmuch as reoxidation by these agents prevents affinity alkylation by bromoacetylcholine, and occupation by the competitive antagonist d-tubocurarine prevents reoxidation. Unlike thiocholine, a weak agonist with a free sulfhydryl that, paradoxically, is reported to oxidize nicotinic receptors in electroplax, the reduced forms, mercaptoacetylcholine and N,N-dimethylamino-4-mercaptoacetylpiperazinium, have no direct redox effects on retinal receptors, but they do protect the receptors against reduction by dithiothreitol.

Acetylcholine↗
PubMed1991

Late-onset congenital adrenal hyperplasia in a group of hyperandrogenic women.

The aim of this study was to determine the prevalence of late-onset congenital adrenal hyperplasia (LOCAH) in a group of hyperandrogenic women presenting with menstrual disturbances and/or infertility. Thirty-five women were evaluated by basal hormonal profiles and underwent ACTH stimulation testing. In this study, 17.1% of women showed evidence of partial 21-OH deficiency (21-OHD), and 5.7% 3 beta-HSD deficiency. Neither basal hormonal levels nor clinical characteristics distinguished women with LOCAH from other hyperandrogenic women. And although the mean basal 17-OH progesterone (17-OHP) level in women with 21-OHD (152 +/- 66 ng/dl) was significantly higher than levels in other hirsute women, 4 of 6 (67%) women with 21-OHD had normal 17-OHP levels. Thus, to identify all affected individuals with partial 21-OHD, our data suggest that hyperandrogenic women with basal unsuppressed 17-OHP levels greater than 100 ng/dl should undergo dynamic testing. With regard to partial 3 beta-HSD deficiency, basal DHEA-S levels greater than the 95th percentile of other hirsute women may be used to screen for this deficiency. In conclusion, LOCAH due to partial steroid enzyme deficiencies are a frequent occurrence in women who present with symptoms of hyperandrogenism and ACTH stimulation remains an important tool in making the diagnosis of enzyme deficiencies.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Alterations in luteal phase progesterone and estradiol production after leuprolide acetate therapy before ovarian stimulation for in vitro fertilization.

The impact of pituitary suppression with a gonadotropin-releasing hormone agonist (GnRH-a) on the luteal phase of in vitro fertilization (IVF) cycles was examined in 21 women who underwent identical stimulation regimens with and without leuprolide acetate pretreatment. The areas under the serum progesterone curves, measured over the 1st 10 days of the luteal phase, were significantly greater in the GnRH-a cycles compared with the non-GnRHa cycles, but when calculated per oocyte retrieved were similar in GnRH-a and non-GnRH-a cycles. In contrast, the areas under the luteal phase serum estradiol curves were significantly less in the GnRH-a cycles. These data suggest that GnRH-a treatment is accompanied by potentially beneficial alterations in the systemic steroidal milieu of the luteal phase of IVF cycles.

Adult↗
PubMed1991

Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age.

A study of 1,478 consecutive in vitro fertilization (IVF) cycles was made to determine if basal follicle-stimulating hormone (FSH) levels and age were independent predictors of IVF performance. Regression analyses indicated independent contributions of both basal FSH and age in predicting cancellation rate, peak estradiol, number of oocytes retrieved, fertilized, and transferred, and total and ongoing pregnancy rates. Miscarriage rate was unrelated to both age and basal FSH. Follicle-stimulating hormone level was a better predictor than age for all outcome variables examined and remained a significant predictor after accounting for age, etiology of infertility, and semen quality. The combined use of age and basal FSH in counseling patients improves the accuracy of prognosis, and may provide an index of functional ovarian reserve ("ovarian age").

Abortion, Spontaneous↗
PubMed1991

Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycles.

We have reported a 36% pregnancy rate (eight of 22 transfers) with the transfer of cryopreserved-thawed embryos in patients with anovulatory or irregular cycles following a protocol using pituitary suppression with leuprolide acetate after preparation of the endometrium with transdermal E2 and i.m. P. This protocol is simple, easy to follow, and safe and could be used in future for all patients with cryopreserved pre-embryos.

Adult↗
PubMed1991

Luteal phase defect: a review of pathophysiology.

Corpus luteum function depends on normal granulosa and theca cell components, which in turn are stimulated by an adequate luteinizing hormone (LH) surge in both duration and amplitude of pulses with LH residual pulses of adequate amplitude during the 14-day luteal span. The granulosa component must be competent to 1) synergize with thecal androgen production for increased estrogen production, 2) develop LH receptors for progesterone production, and 3) mature the egg cytoplasmically. The theca component must be capable of inducing angiogenesis factor to increase follicular blood supply and must be responsive to an LH pulse and human chorionic gonadotropin for corpus luteum rescue. The corpus luteum defect with a normal 14-day span is related either to an inadequate granulosa cell or to an inadequate LH surge, but a fairly normal LH pulse and theca cell response. The short luteal phase defect is related to a poor LH surge and an absent or extremely poor LH pulse. Diagnostic studies have indicated that the endometrial biopsy is the most efficient diagnostic method. Severe luteal defects can be diagnosed by a progesterone assay if the entire cycle is assayed, but single or even multiple progesterone assays are unreliable. The etiology is multifactorial and usually is related to the hypothalamic-pituitary factors influencing the LH surge, rather than to ovarian factors. Factors may vary from cycle to cycle, making it important to determine that the defect is repetitive. The specific etiology is often difficult to determine; substitution progesterone therapy is the most satisfactory treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗
PubMed1990

Ovarian stimulation for in vitro fertilization in low-responder patients using pulsatile intravenous follicle stimulating hormone.

There is a subset of patients who fail to respond adequately to exogenous gonadotropin stimulation for in vitro fertilization (IVF). In this study, six such low-responder patients who had inadequate stimulations with high-dose intramuscular (im) follicle stimulating hormone (FSH) were treated in a subsequent cycle with pulsatile intravenous (iv) FSH. A paired analysis was performed to compare the cycles using high-dose im FSH with those using pulsatile iv FSH. Trough serum FSH levels were significantly higher with pulsatile iv FSH. No significant difference was noted in the stimulation characteristics or the number or quality of oocytes retrieved and embryos transferred. No pregnancies occurred in either group. While pulsatile iv administration of gonadotropin increases serum FSH levels, it does not appear to have a major impact on follicular stimulation or outcome in low-responder patients undergoing IVF.

Female↗
PubMed1990

Ovarian stimulation for in vitro fertilization using pure follicle-stimulating hormone with and without gonadotropin-releasing hormone agonist in high-responder patients.

There is a distinct pattern of response to gonadotropin stimulation in some patients marked by high peak estradiol (E2) levels, multifollicular ovarian response, and elevated basal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios. We reviewed the stimulation profiles of five such high-responder patients who failed to conceive during in vitro fertilization with ovarian stimulation using pure FSH. All patients had baseline LH/FSH greater than 1.5 and peak E2 greater than 800 pg/ml. One cycle was canceled prior to hCG administration because of marked ovarian response (E2 greater than 2500 pg/ml, multiple small follicles). In a subsequent cycle, all patients were pretreated with the gonadotropin releasing-hormone agonist (GnRHa) leuprolide acetate for 10-14 days prior to initiation of FSH for ovarian stimulation. Leuprolide was continued until the day of hCG administration. During cycles using GnRHa, there was a statistically significant decrease (P less than 0.05) in serum FSH on day 3 (less than 5 vs 8.3 mIU/ml), serum E2 on day 3 (14.6 vs 34.6 pg/ml), and peak serum E2 (1197.6 vs 1923.0 pg/ml). Patients during cycles with GnRHa had a greater number of preovulatory (8.6 vs 3.0) and total (12.4 vs 6.0) oocytes retrieved (P less than 0.05). The fertilization rate of preovulatory oocytes was also higher during cycles using GnRHa (83 vs 64%). Two pregnancies occurred in the cycles pretreated with GnRHa. These preliminary data indicate that in high-responder patients, a combination of GnRHa and pure FSH results in lower E2 levels during the stimulation cycle and a greater number of total and mature oocytes retrieved and fertilized.

Adult↗
PubMed1990

Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression.

This study compares the use of human menopausal gonadotropin (hMG) versus follicle-stimulating hormone (FSH), after gonadotropin-releasing hormone agonist (GnRH-a) suppression for in vitro fertilization. Thirty-seven patients were randomized to ovarian stimulation with either hMG or pure FSH. The GnRH-a leuprolide acetate was administered to all patients beginning in the midluteal phase of the prior cycle and continuing until the day of human chorionic gonadotropin (hCG) administration. There were no significant differences between hMG and FSH cycles with regard to the day of hCG administration, mean peak estradiol levels, number of ampules of medication used, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that there is no significant difference between hMG and FSH stimulation when used in conjunction with GnRH-a.

Adult↗
PubMed1990

High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients.

In an attempt to improve their outcome with in vitro fertilization (IVF), 34 low-responder patients were stimulated with six ampules of follicle-stimulating hormone (FSH) daily starting on day 1 (n = 17) or day 2 (n = 17) of their menstrual cycles. The stimulated cycles showed a mean peak estradiol of 443 +/- 173 pg/mL, mean days of human chorionic gonadotropin of 7.6 +/- 1.4, 2.67 +/- 1.5 preovulatory oocytes per retrieval, and 2.56 +/- 1.3 oocytes per transfer. Three clinical pregnancies resulted after 25 embryo transfer cycles (12%). With paired analysis, we compared 8 patient cycles with prior six ampules of FSH stimulation starting on day 3; all parameters examined showed no significant differences. In a comparison of 22 patient cycles with prior 4 ampules of FSH stimulation on cycle day 3, no significant differences in any parameters were observed except in the higher number of ampules used in the present study. We conclude that high-dose FSH stimulation at the onset of the menstrual cycle does not improve the IVF outcome in low-responder patients.

Adult↗
PubMed1990

Killing of Mycobacterium tuberculosis by neutrophils: a nonoxidative process.

To determine the role of oxygen radicals in the killing of Mycobacterium tuberculosis by neutrophils, the effects of free-radical inhibitors and enzymes, catalase, superoxide dismutase, taurine, deferoxamine, and histidine were evaluated. Changes in the viability of M. tuberculosis were determined by agar plate colony counts and a radiometric assay. No impairment in killing was seen with any of the inhibitors or enzymes. Patients with chronic granulomatous disease (CGD) have a defect in the NADPH oxidase pathway, causing their neutrophils to be unable to generate oxygen radicals. If these radicals are involved in killing, then CGD neutrophils should be less effective killers of M. tuberculosis than normal neutrophils. There was no evidence by either measure of M. tuberculosis viability that CGD neutrophils were less bactericidal than normal neutrophils. Killing by normal neutrophils was also effective in the absence of serum. These results lead to the conclusion that the mechanism by which M. tuberculosis is killed by neutrophils is independent of the oxygen metabolic burst.

Catalase↗
PubMed1990

Non-functional ovarian cysts do not affect ipsilateral or contralateral ovarian performance during in-vitro fertilization.

Reports on the significance of ovarian cystic structures during in-vitro fertilization (IVF) have been conflicting. This study examined the effect of such structures on ovarian performance during IVF. Twenty-one patients with one or more cystic structures of 20-50 mm in diameter, detected on day 6 of the menstrual cycle, were compared to 35 non-cystic controls. Differences (cyst versus non-cyst) included basal oestradiol (E2) levels (40 +/- 4.8 versus 29 +/- 2.0 pg/ml; P less than 0.01), ampoules of gonadotrophins administered (24 +/- 2 versus 16 +/- 1; P less than 0.001) and peak E2 concentrations (415 +/- 45 versus 744 +/- 88 pg/ml; P less than 0.05). There were no differences in the number of follicles aspirated or oocytes retrieved. In 19 patients with unilateral structures, the ipsilateral ovary produced fewer follicles (2.5 +/- 0.5 versus 3.9 +/- 0.6; P less than 0.05); however, there were no differences in the number or maturity of oocytes recovered. Since the numbers of oocytes recovered were equivalent in the presence or absence of ovarian cystic structures, their presence is not an indication to cancel an IVF cycle.

Adult↗
PubMed1990

[The GnRH precursor is present in the anterior pituitary gland and an important increase of its content precedes serum LH surge induced by estradiol-17 beta in female primates].

Estradiol-17 beta (E2 17 beta) is well known to evoke a preovulatory-like LH surge in ovariectomized monkeys even in the absence of the integrity of the hypothalamo-pituitary connections. LH release from the anterior pituitary (AP) is reliant on stimulation by hypothalamic GnRH which is derived from proteolytic cleavage of a precursor (designated Pro-GnRH-GAP) which also results in the production of an associated peptide (GAP). The present study examined the effects of E2 17 beta on the hypothalamic content of Pro-GnRH-GAP, GnRH and GAP while incidental observations revealed the presence of Pro-GnRH-GAP and its products in the AP. Changes in GnRH and GAP were closely related at all times after E2 17 beta treatment. However, the pattern of change in the hypothalamus and AP was inversely related. Pro-GnRH-GAP levels remained unchanged in the hypothalamus whereas in the AP the peptide increased markedly (48 hrs. post E2 17 beta) prior to the LH surge and declined to low levels (72 hrs. post E2 17 beta) at the time of the LH surge. The increase in Pro-GnRH-GAP in the AP that precedes the rise in GnRH and accompanying LH surge by 24 hrs. strongly indicates that AP GnRH is more important than hypothalamic GnRH for the mediation of the E2 17 beta-induced LH surge in female primate.

Animals↗