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R J Chang

Publications and source records attributed to R J Chang.

At least 55 records · Page 3Linked to original sources
PubMed1988

Regulation of the number of alpha-bungarotoxin binding sites in cultured chick myotubes by a 1,4 dihydropyridine calcium channel antagonist.

Calcium has been suggested as the second messenger link between skeletal muscle activity and AChR gene expression and synthesis. We have compared the concentrations of the Ca2+ channel antagonists D600 and nisoldipine needed both to block Ca2+ uptake into cultured myotubes and to increase AChR expression. The good correspondence between these two measurements and the use of the highly specific Ca2+ channel antagonist nisoldipine strengthens the hypothesis that AChR expression is regulated by levels of intracellular Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Identification of a approximately 170K subunit of the cardiac calcium channel using a monoclonal antibody to the skeletal muscle dihydropyridine receptor.

Our newly isolated monoclonal antibody (#78) specifically interacts with the 170Kd 1,4 dihydropyridine binding component of the skeletal muscle calcium channel. Dihydropyridine receptor (DHPR) from rabbit skeletal muscle and canine cardiac membranes were purified by monoclonal antibody #78 affinity chromatography. We show that DHPR from canine cardiac membranes like DHPR from rabbit skeletal membranes contain a approximately 170Kd polypeptide to which antibody #78 immunoblots under both reducing and non-reducing conditions.

Animals↗
PubMed1988

An assay using embryo aggregation chimeras for the detection of nonlethal changes in X-irradiated mouse preimplantation embryos.

We have developed a short-term in vitro assay for the detection of sublethal effects produced by very low levels of ionizing radiation. The assay utilizes mouse embryo aggregation chimeras consisting of one irradiated embryo paired with an unirradiated embryo whose blastomeres have been labeled with fluorescein isothiocyanate (FITC). X irradiation (from 0.05 to 2 Gy) and chimera construction were performed with four-cell stage embryos, and the chimeras were cultured for 40 h to the morula stage. The morulae were partially dissociated with calcium-free culture medium and viewed under phase contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution of irradiated (unlabeled) and control (FITC labeled) embryos per chimera. In chimeras where neither embryo was irradiated, the ratio of the unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.50 (17.8 +/- 5.6 cells per unlabeled embryo and 17.4 +/- 5.5 cells per FITC-labeled partner embryo). However, in chimeras formed after the unlabeled embryos were irradiated with as little as 0.05 Gy, the ratio of unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.43 (P less than 0.01). The apparent decreases in cell proliferation were not observed in irradiated embryos that were merely cocultured with control embryos, regardless of whether the embryos were zona enclosed or zona free. We conclude that very low levels of radiation induce sublethal changes in cleaving embryos that are expressed as a proliferative disadvantage within two cell cycles when irradiated embryos are in direct cell-to-cell contact with unirradiated embryos.

Animals↗
PubMed1987

Reproductive effects of chlorpromazine exposure to female mice: cell proliferation disadvantage revealed by the Chimera Embryo Assay.

Administration of chlorpromazine-HCl at 5 to 15 mg/kg bodyweight to pregnant CD-1 mice at 24 h after human chorionic gonadotropin (hCG) (20-23 h after mating) inhibited blastocyst formation and reduced the cell number of embryos recovered at 95 h after hCG. When embryos are recovered at the two- to four-cell stage (48-50 h after hCG) and cultured for an additional 47 h (to 95 h after hCG) or 72 h (to 120 h after hCG), blastocyst formation and embryo cell number were similarly reduced. When the dose range was reduced to 0.5 to 2 mg/kg bodyweight, no significant effect of the drug was observed on blastocyst formation or on embryo cell number. However, when aggregation chimeras were formed between embryos recovered from drug-exposed females and from untreated females, a decrease in cell proliferation rate of the embryo from the drug-exposed female was observed at a dose of 2 mg/kg bodyweight. This result indicates that exposing pregnant mice to chlorpromazine-HCl at doses as low as 2 mg/kg bodyweight can induce a potential for decreased cleavage rate in their pre-implantation embryos that can be revealed by challenging those embryos by direct contact with embryos from nonexposed females. Finally, when four-cell stage embryos recovered from untreated females cultured in the presence of chlorpromazine (0.1-25 mM), blastocyst formation and embryo cell number were significantly reduced in a dose-dependent manner. This last result suggests that in vivo the drug may act directly on the embryo from the pronuclear stage to the early morula stage of development.

Animals↗
PubMed1987

Detection of antisperm antibodies: their localization to human sperm antigens that are transferred to the surface of zona-free hamster oocytes during the sperm penetration assay.

The authors have developed an extension of the sperm penetration assay for detecting serum immunoglobulins to sperm antigens that are transferred to the plasma membrane of a sperm-penetrated hamster oocyte. After the hamster oocytes have been scored for sperm penetration by observing for the presence of swollen sperm heads, they are incubated in serum followed by either a 20-minute treatment with rhodamine-conjugated protein A (which binds to most subclasses of IgA, IgG, and IgM) or a 2-hour incubation in guinea pig serum (complement). Positive fluorescence indicates that the serum contains antibodies to sperm antigens that were transferred to the surface of an oocyte during gamete fusion. Complement-mediated lysis indicates that the immunoglobulin that is bound can also fix complement. The advantages of this assay for detection of serum antisperm antibodies are that it is an extension of a widely used assay, is rapid and requires readily available reagents and equipment, can detect most subclasses of IgA, IgG, and IgM, detects antibodies to those sperm antigens that may be transferred to the oocyte during fertilization, and indicates whether the detected antisperm antibodies can mediate complement-dependent lysis of the fertilized oocyte.

Animals↗
PubMed1987

Are we exploiting the infertile couple?

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

Advertising↗
PubMed1987

Antisperm antibodies bind with different patterns to sperm of different men.

Immunologic infertility is an important area of current clinical research. The immunobead test is a laboratory method that identifies the classes of antisperm antibodies and their binding sites on the sperm surface. In this study we have investigated the variability in the pattern of antibody binding to spermatozoa after passive transfer from blood serum. Serum from a single donor containing antisperm antibodies of the IgG class was used in all experiments. The spermatozoa from 27 semen donors were found to differ significantly in the degree and location of immunobead binding after exposure to this serum. There was substantial day-to-day variability in the results for individual semen donors and the overall variability in test results was significantly greater when a number of semen donors was used rather than a single donor. These data suggest that details of antisperm antibody binding after passive transfer from body fluids may depend on the sperm donor. The design of research studies involving antibody transfer must take this source of variability into account.

Adult↗
PubMed1987

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.

Androgens↗
PubMed1987

The effect of the ergoline derivative, CU 32-085, on prolactin secretion in hyperprolactinemic women.

Twelve hyperprolactinemic women were administered the alpha aminoergoline derivative, CU 32-085 (Sandoz, Inc., East Hanover, NJ), in order to determine its effect on prolactin (PRL) secretion. The mean pretreatment serum PRL level was 145.0 +/- 11.5 ng/ml. Significant declines of serum PRL occurred with total daily doses of CU 32-085 of 0.1 to 0.5 mg (P less than 0.001). The magnitude of response to therapy was dose-related. In six patients, PRL levels were reduced to less than 25 ng/ml; this effect lasted at least 24 hours after intake of a single dose. In the other six patients, the response was less dramatic. No subjects developed adverse cardiovascular side effects. The results of this study demonstrate that CU 32-085 exhibits a clinically significant dopaminomimetic action on PRL secretion in hyperprolactinemic women.

Adenoma↗
PubMed1986

Effects of interferon-gamma and tumor necrosis factor-alpha on the expression of an Ia antigen on a murine macrophage cell line.

Cultures of the murine myelomonocytic cell line, WEHI-3, can be induced to express the Class II MHC antigen, I-A, by incubation with rMuIFN-gamma and/or rHuTNF-alpha. A 24-hr incubation with the combination of rMuIFN-gamma (5.6 ng/ml) and rHuTNF-alpha (13 ng/ml) induced the highest level of expression in the cell population (more than 90%), followed by rMuIFN-gamma (75%) and rHuTNF-alpha (33%). Comparison of the level of mRNA for the heavy chain subunit of the I-A molecule, A alpha, indicates that the combination is 10 and 40 times as stimulatory as rMuIFN-gamma and rHuTNF-alpha alone, respectively. Each cytokine treatment induced a time-dependent increase in the level of A alpha mRNA over the 72 hr of incubation examined, although the combination continued to elevate the level of A alpha mRNA above that induced by either cytokine alone. The findings reported here demonstrate that the monokine rHuTNF-alpha can induce I-A antigen expression and A alpha mRNA. Furthermore, stimulation by the combination of rHuTNF-alpha and rMuIFN-gamma is more than additive, relative to the effects of each cytokine as individual agents.

Animals↗
PubMed1986

Treatment of severe androgen excess due to ovarian hyperthecosis with a long-acting gonadotropin-releasing hormone agonist.

A 31-year-old nulligravid patient presented with irregular menses, severe hirsutism, and infertility. Evaluation revealed marked increases of serum androstenedione and testosterone levels and a possible ovarian mass. At operation a cystic teratoma was removed from the left ovary and bilateral wedge resection revealed severe ovarian hyperthecosis. After operation only a transient decrease of androstenedione and testosterone was noted and the patient failed to ovulate or improve clinically. Subsequently a long-acting gonadotropin-releasing hormone agonist was administered daily for 6 months, which reduced circulating delta 4-steroids and estrogens to levels approximating those of castrated women. Immediately after discontinuation of treatment, ovulation induction was successfully achieved with human menopausal gonadotropin. This report introduces a new therapeutic approach to the problem of severe ovarian hyperthecosis and may provide an opportunity for childbearing in these patients.

Adult↗
PubMed1986

The effect of bromocriptine on gonadotropin and steroid secretion in polycystic ovarian disease.

Use of bromocriptine in some women with polycystic ovarian disease (PCO) has resulted in ovulation induction, although a mechanism has not been established. The purpose of this study was to determine the effect of bromocriptine on gonadotropin and steroid secretion in this disorder. Two groups of seven patients were given bromocriptine at a dose of either 5 mg/day for 2 months or 10 mg/day for 1 month. Ten normal ovulatory women served as controls. In PCO patients, mean serum levels of LH, bioactive LH, androstenedione, testosterone, unbound testosterone, dehydroepiandrosterone sulfate (DHEA-S), and estrone were significantly greater (P less than 0.05) than those of normal women, whereas FSH, PRL, dihydrotestosterone, 3 alpha-androstanediol, and estradiol were not different. Assessment of gonadotropin secretion before and during treatment revealed that basal levels, episodic secretion, and responses to GnRH (25 micrograms, iv) were unaltered by either dose of bromocriptine. Of the remaining hormones, PRL and DHEA-S significantly decreased in response to both doses. There were no changes in the clinical status of patients during treatment. These findings indicate that in PCO patients with normal PRL levels, gonadotropin secretion is unaltered by bromocriptine therapy. The concomitant declines of PRL and DHEA-S confirm previous data reported for this syndrome and suggest a role for PRL in the production of adrenal androgens.

Androstenedione↗
PubMed1986

Pituitary tumors secreting growth hormone and prolactin.

The pathophysiology of functional adenomas of the anterior pituitary gland can be understood in the context of the central neural control of anterior pituitary secretion and by the fact that the cell types of the anterior pituitary gland generally express a single polypeptide hormone. Functional pituitary adenomas arise de novo from one or more of these cell types, but a defect in hypothalamic regulation can contribute to tumorigenesis and sometimes result in persistent tumor recurrence despite local surgical cure. The recent advances in molecular biology, radioimmunoassay, neuroradiology, and transsphenoidal microneurosurgery techniques have greatly improved our understanding of the pathophysiology of these tumors, enhanced diagnostic accuracy, and led to newer medical and surgical therapeutic approaches. This conference reviews the molecular and cellular pathophysiology, causes, diagnosis, clinical features, and medical and surgical management of the two common functional pituitary adenomas, prolactinoma and somatotropinoma.

Adenoma↗
PubMed1986

Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion.

Six nonobese women with polycystic ovarian disease (PCOD) showed significant hyperinsulinemia, compared with controls after oral glucose (P less than 0.05). As an indicator of insulin sensitivity, in vitro proliferation of erythrocyte progenitor cells of PCOD subjects exposed to physiologic concentrations of insulin was significantly blunted (P less than 0.001). Monocyte insulin receptor binding was not impaired in the PCOD subjects. Three of the PCOD patients were treated with a long-acting gonadotropin-releasing hormone agonist for 6 months, which resulted in marked suppression of ovarian androgen secretion but no demonstrable changes in in vivo or in vitro indicators of insulin resistance. Thus insulin resistance in PCOD subjects appears to be unrelated to ovarian hyperandrogenism (or acanthosis or obesity). Although certain tissues are insulin-resistant in PCOD patients, the ovary may remain sensitive and overproduce androgens in response to high circulating insulin levels.

Adult↗
PubMed1985

Evolution of antibody structure and effector functions: comparative hemolytic activities of monomeric and tetrameric IgM from rainbow trout, Salmo gairdnerii.

Monomeric and tetrameric IgM anti-haptin antibodies isolated from the sera of rainbow trout (S. gairdnerii) by immunoaffinity chromatography were compared both immunochemically and with regard to their functional abilities to lyse haptenated trout erythrocytes in the presence of trout complement. The two populations had similar binding affinities for hapten and apparently identical L chains, but differed in H chain peptide maps and immunoreactivity with rabbit anti-trout H chain serum. These differences could not be attributed to J-chain. The abilities of the two antibody subpopulations to activate C to lyse haptenated trout erythrocytes also differed dramatically. Such functional differences are not simply explained by the greater avidity of the tetrameric form since preliminary studies show that the monomeric form of trout IgM activates C via an alternative pathway mechanism while the tetrameric form activates both classical and alternative pathway mechanisms. Results suggest divergent evolution of antibody structures involved in the familiar effector functions (C activation, transport, etc.).

Animals↗
PubMed1985

Acute ovarian responses to a long-acting agonist of gonadotropin-releasing hormone in ovulatory women and women with polycystic ovarian disease.

A long-acting agonist of gonadotropin-releasing hormone (GnRH-a, 100 micrograms/day) was administered daily for 14 days in four patients with polycystic ovarian disease (PCOD) and eight ovulatory women (OW) to determine acute hormone responses. Initiation of GnRH-a treatment in OW on day 5 of their menstrual cycles (OW-day 5) stimulated a greater acute rise of serum follicle-stimulating hormone (FSH) than that seen in OW beginning treatment on day 2 (OW-day 2) or PCOD patients. FSH levels fell to baseline values with repeated injections, whereas luteinizing hormone levels remained elevated in all patients. An acute rise and progressive fall of estradiol (E2) was found in all groups. The OW-day 5 group demonstrated a secondary increase, which by day 14 was clearly greater than that found in the other groups. This secondary increase of E2 in the OW-day 5 group was associated with lower abdominal pain, whereas OW-day 2 and PCOD patients were asymptomatic. For comparison, human menopausal gonadotropin (150 IU/day for 3 days) stimulated a significantly greater increase of E2 in OW-day 5 than in PCOD patients. These studies indicate that daily GnRH-a administration induced variable effects on ovarian function, which depended on when it was begun during the menstrual cycle and whether it was given to ovulatory or PCOD subjects. In addition, abdominal discomfort associated with GnRH-a use in regularly OW can be avoided by commencing agonist administration earlier in their menstrual cycles.

Abdomen↗