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Biomedical subjects

G S Jones

Publications and source records attributed to G S Jones.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

The domain model for eukaryotic DNA organization. 2: A molecular basis for constraints on development and evolution.

A model for eukaryotic DNA organization has been proposed in which DNA regulatory processes depend on multiple site-specific DNA-nuclear matrix interactions throughout a DNA domain. In this model gene regulation depends on combinations of a few control factors in a cell to activate cell type-specific genes. This model suggests simple molecular mechanisms for organismal development which can account for sequential activation of appropriate groups of genes throughout development and for specific constraints on developmental pathways. Additionally, these suggested developmental pathways are consistent with mechanisms of evolution in which gradualism and punctuated equilibrium are not exclusive of one another and are interrelated mechanisms of evolution that are both induced by specific chromosomal mutations.

Animals↗
PubMed1989

High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low-responder patients for in vitro fertilization.

Follicle-stimulating hormone (FSH) was used in high doses (6 ampoules/day:6FSH) for ovarian hyperstimulation for in vitro fertilization in women with a previous poor response to stimulation with the equivalent of "4FSH." Luteinizing hormone levels did not differ between stimulations, but both FSH and estradiol levels were higher in the 6FSH compared to the 4FSH cycle. There were fewer cancellations in the 6FSH cycle, but similar numbers of preovulatory oocytes were retrieved, fertilized, and transferred. The pregnancy rates per attempt and retrieval were higher in the 6FSH cycle. We conclude that raising and maintaining FSH levels during stimulation in low responders reduced cancellations and may improve in vitro fertilization outcome.

Adult↗
PubMed1989

Impact of leuprolide acetate on the response to follicular stimulation for in vitro fertilization in patients with normal basal gonadotropin levels.

Fifteen women with normal basal gonadotropin levels and adequate responses to conventional gonadotropin stimulation for in vitro fertilization (IVF) were pretreated with leuprolide acetate (LA) beginning in the midluteal phase prior to a repeat IVF attempt. A significantly longer duration of stimulation requiring a significantly higher total dosage of gonadotropins was observed in LA cycles. The number of preovulatory oocytes retrieved and preembryos transferred was significantly higher in LA cycles. Six of 15 women (40%) had cryopreservation of supernumerary preembryos in LA cycles, versus none in non-LA cycles; 22% of preovulatory oocytes aspirated in LA cycles were available for cryopreservation for future transfer. Five pregnancies occurred in the 15 LA cycles. IVF patients with normal basal gonadotropin levels and normal responses to conventional gonadotropin stimulation benefit from LA pretreatment.

Adult↗
PubMed1989

Gonadotropin stimulation protocols in the Norfolk IVF program--1988.

A standard FSH/hMG stimulation protocol applied to all patients does not yield optimum results. In the Norfolk program it has been found that the determination of FSH/LH ratio on day 3 of the menstrual cycle provides a predictive signal of the likelihood of a good or bad response to a standard protocol. If the FSH is high in relation to LH, the patient will likely be a low responder and/or approaching the menopause. A regime of high-dose pure FSH seems to improve the number of eggs in this group and therefore the pregnancy rate. On the other hand, if the FSH/LH ratio is very low, that is, the patient has a high LH, the patient is generally a high responder and produces many eggs, but in some instances the quality of eggs is suspect, and the pregnancy rate is low in a particular subset of high responders. The use of GnRHa and/or minimal stimulation with FSH or hMG seems to improve the pregnancy rate.

Female↗
PubMed1989

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization.

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.

Estradiol↗
PubMed1989

In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist.

In this study, in-vitro fertilization (IVF) cycles were examined in patients with endometriosis who received gonadotrophin releasing hormone agonist (GnRHa) therapy in an effort to improve their response to stimulation. Twelve patients treated with an identical gonadotrophin stimulation protocol, with and without GnRHa, were evaluated using paired analysis. In the GnRHa cycles, the total number of oocytes retrieved and transferred per cycle was higher than in the control cycles. In addition, use of the agonist lowered the cancellation rate from 33 to 0%, while a trend towards better pregnancy results was observed. When analysed according to the stage of the disease, the patients with stage III or IV endometriosis had a more dramatic improvement with GnRHa. These data suggest that GnRHa therapy may be beneficial in some patients with endometriosis undergoing IVF.

Embryo Transfer↗
PubMed1988

Monitoring gonadotropin-stimulated cycles for in vitro fertilization and embryo transfer.

One hundred fifty-one cycles stimulated with human menopausal gonadotropin (hMG) and/or follicle-stimulating hormone (FSH) were analyzed retrospectively to determine the relationship of the monitoring parameters used: serum estradiol (E2), transvaginal sonographic follicular size, and peripheral biologic estrogen response, with harvests and pregnancies resulting from in vitro fertilization and embryo transfer. Mean +/- SE serum E2 levels were higher on the day of human chorionic gonadotropin (hCG) administration in the miscarriage group (689.4 +/- 27.5 pg/ml) than in the nonpregnant group (527.7 +/- 25.8 pg/ml) (P = 0.018) and highest in the ongoing pregnancy group (734.6 +/- 66.5 pg/ml) (P = 0.003). When two or more preovulatory oocytes (preovs) were retrieved, the mean E2 levels were higher (622.3 +/- 27.3 pg/ml) than if zero or one preov was retrieved (378.4 +/- 43.5 pg/ml) (P = 0.001). The mean diameter of the two largest follicles at the time of hCG administration was significantly greater (14.7 mm) in the group with two or more preovs retrieved than in the group with zero or one preov (13.3 mm) (P = 0.001). The relative probability of achieving a pregnancy was best predicted by the presence of two follicles greater than or equal to 16 mm in diameter on transvaginal ultrasound examination and was 1.63 times greater than that of all patients in this series.

Embryo Transfer↗
PubMed1988

Mechanisms and factors of early pregnancy wastage in in vitro fertilization-embryo transfer patients.

Although the pregnancy rate per transfer of the Norfolk In Vitro Fertilization-Embryo Transfer (IVF-ET) program has been reported as between 25% and 35%, the viable pregnancy rate per transfer is only 15% to 20%. An understanding of the mechanism(s) and etiologic factors of miscarriage among IVF patients might suggest changes that could prevent some early pregnancy wastage. Forty-seven consecutive single pregnancies and 26 miscarriages (October 1985 to November 1986) were included in this study. Factors such as implantation time, date of corpus luteum rescue (CLR), embryo quality, and corpus luteum activity after rescue were studied and compared between term pregnancy and miscarriage groups. Results are discussed in detail in this paper.

Abortion, Spontaneous↗
PubMed1988

The value of basal and/or stimulated serum gonadotropin levels in prediction of stimulation response and in vitro fertilization outcome.

The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.

Abortion, Spontaneous↗
PubMed1988

Timing of oocyte retrieval in cycles with a spontaneous luteinizing hormone surge in a large in vitro fertilization program.

Forty-four cycles with a spontaneous luteinizing hormone (LH) surge among 377 in vitro fertilization (IVF) patients were studied for outcome with different timing of oocyte retrieval. Mean number of preovulatory oocytes per retrieval and per transfer was significantly less in these cycles than in controls. Mean number of preovulatory oocytes per retrieval and per transfer was significantly higher when the human chorionic gonadotropin (hCG)-retrieval interval was greater than 35 hours, compared with less than 24 hours. In cycles with an hCG-retrieval interval of less than 24 hours, percentage of preovulatory oocytes was higher when serum estradiol (E2) decreased by greater than 15% on the morning after hCG administration compared with a plateau or an increase in serum E2. Timing oocyte retrieval after spontaneous LH surge should consider the hCG-retrieval interval and changes in E2 levels after hCG administration; this may avoid cancellation for many patients.

Adult↗
PubMed1988

Follicular atresia associated with concurrent initiation of gonadotropin-releasing hormone agonist and follicle-stimulating hormone for oocyte recruitment.

The ability of gonadotropin-releasing hormone agonist (GnRHa) to cause an initial stimulation of serum gonadotropins was used for follicular recruitment for in vitro fertilization (IVF) in 12 patients with a history of low estradiol (E2) response to conventional gonadotropin stimulation. Stimulation was initiated on cycle day 3 with concurrent administration of leuprolide (1 mg/day subcutaneously) and follicle stimulating hormone (FSH, 4 ampules/day intramuscularly). An 8-fold increase in basal serum luteinizing hormone (LH) and a 4-fold increase in basal serum FSH was seen on cycle day 4. Serum progesterone levels rose significantly by day 6. When compared to prior IVF attempts in these patients, the mean day of human chorionic gonadotropin administration and corresponding E2 levels were not significantly different. More atretic oocytes and fewer preovulatory oocytes were retrieved using GnRHa, and no increase was seen in total oocytes retrieved. One patient was canceled for poor E2 response, and one patient conceived, with a current viable pregnancy. It is concluded that concurrent initiation of leuprolide and FSH stimulation on cycle day 3 in patients with prior low response does not improve oocyte recruitment, and the high LH environment generated from initial stimulation of the agonist may be detrimental to normal oocyte development.

Embryo Transfer↗
PubMed1988

Synthesis and biologic evaluation of 1-[11C]-3,3-dimethylheptadecanoic acid.

1-[11C]-3,3-dimethylheptadecanoic acid [( 11C]DMHDA) has been prepared for evaluation as a potential myocardial metabolism indicator based on an expected intrinsic stability toward beta-oxidative metabolic processes. Synthesis of this novel branched-chain fatty acid was accomplished by copper-catalyzed addition of tetradecylmagnesium bromide to diethylisopropylidenemalonate. Subsequent saponification and decarboxylation afforded 3,3-dimethylheptadecanoic acid (DMHDA) that was converted to the corresponding alkyl bromide by means of a modified Hunsdiecker reaction. Carboxylation of 2,2-dimethylhexadecylmagnesium bromide with 11CO2 gave [11C]DMHDA. Carbon-11 DMHDA showed moderate myocardial uptake in fasted rats, albeit lower than that reported for the 3-monomethyl analog. Considerable washout of radioactivity from the heart was also observed over the first 30 min postinjection. Imaging in dogs likewise showed disappointing heart uptake with much higher localization in the lung. These data suggest that gem-dimethyl substitution of the beta-position in long chain fatty acids is not only insufficient for enhanced myocardial uptake and retention, but also, may be deleterious when compared with beta-monomethylation.

Animals↗
PubMed1987

Results of in vitro fertilization attempts in women 40 years of age and older: the Norfolk experience.

Twenty-nine patients 40 years of age or older were stimulated with gonadotropins, starting on day 3 of the cycle, in a total of 64 cycles (January 1983 to June 1985) for multiple follicular development for in vitro fertilization. Most patients' infertility was due to tubal disease (n = 8) or pelvic endometriosis (n = 14). The mean number of preovulatory and immature oocytes recovered per laparoscopy was 2.53 +/- 1.73 and 1.57 +/- 1.58, respectively. There were no statistically significant differences between the number of preovulatory and immature oocytes harvested, fertilized, or transferred in this group and the number in patients younger than 40 years of age. No statistically significant differences were observed between peripheral estradiol and progesterone levels in patients 40 years of age or older and levels in patients 39 years of age or younger. There were 15 pregnancies in this group of patients, for a pregnancy rate of 23.4% per stimulated cycle, 27.7% per laparoscopy, and 29.4% per transfer. The ongoing pregnancy rate (12%) was lower, and the total abortion rate (60%) was higher, in patients 40 years of age or older in comparison with patients 39 years of age or younger. Patients 40 years of age or older should be counseled regarding the high abortion rate in this group.

Adult↗
PubMed1987

Familial hypersecretion of adrenal androgens transmitted as a dominant, non-HLA linked trait.

Clinical evidence of adrenal androgen hyperfunction (premature pubarche, hirsutism, amenorrhea) occurred in the studied proband, her mother, maternal aunt (twin sisters), and maternal great-grandmother. The basal levels of androgen in the first three were variably elevated. In all the members of this family who were tested, the response of 17-hydroxyprogesterone and progesterone to adrenocorticotropic hormone stimulation was either normal or of the type seen in heterozygotes for congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Of particular importance is the fact that neither the proband nor her mother or maternal aunt had the type of response seen in homozygotes presenting the attenuated form of congenital adrenal hyperplasia. The disorder appears to be a familial condition resulting in excessive levels of adrenal androgens beginning during childhood years, causing hirsutism and amenorrhea and interfering with normal pubertal and adult ovarian function. Glucocorticoid therapy suppresses adrenal androgen levels; in two individuals, conception occurred twice in each during such treatment in otherwise amenorrheic individuals. The pattern of transmission of the disorder appears to be either autosomal or X-linked dominant, and not linked to the homologous leucocytic antibodies (HLA) region of the sixth chromosome.

Adolescent↗