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Biomedical subjects

A F Haney

Publications and source records attributed to A F Haney.

At least 91 records · Page 5Linked to original sources
PubMed1985

Steroidogenesis in porcine atretic follicles: loss of aromatase activity in isolated granulosa and theca.

To evaluate the mechanisms involved in the reduction of estrogen concentrations in porcine follicular fluid during atresia, nonatretic and atretic follicles ranging from 4 to 7 mm in diameter were selected. Follicular fluid estrogen concentrations were 7-16-fold less in the atretic follicles. Isolated granulosa cells from atretic follicles demonstrated a significant reduction in aromatase activity and in follicle-stimulating hormone (FSH)-induced progesterone production in vitro compared to granulosa cells from nonatretic follicles. Isolated theca from atretic follicles also demonstrated a reduction in estrogen production. However, androgen concentrations were equivalent in the follicular fluid of atretic and nonatretic follicles, and theca from atretic follicles maintained testosterone and androstenedione production in vitro. The loss of thecal aromatase activity with atresia is not secondary to a reduction in FSH responsiveness, since FSH did not increase thecal progesterone production in vitro. Cell degeneration also does not account for the reduction in thecal estrogen production, since both androgen output in vitro and follicular fluid androgen concentrations were maintained. These data thus demonstrate that a mechanism other than reduced FSH responsiveness must account for the selective loss of thecal aromatase activity in this stage of atresia.

Androstenedione↗
PubMed1985

The pathologic spectrum of uterotubal junction obstruction.

Excised tubal segments from 42 women with uterotubal junction obstruction were studied histologically to evaluate the pathologic spectrum of disease and correlate this with clinical data. The most frequent lesion encountered was obliterative fibrosis (38.1%), confirmed by connective tissue stains, which was not associated with cornual nodularity. Other pathologic entities included salpingitis isthmica nodosa (23.8%), intramucosal endometriosis (14.3%), and chronic tubal inflammation (21.4%). Intramucosal endometriosis was distinguishable from salpingitis isthmica nodosa by virtue of its unique stroma confirmed by connective tissue staining. Women with previous pregnancies were included in all the groups. In all instances, the obstruction was present in the transmural portion of the tube and extended a variable distance into the isthmic segment. These observations on uterotubal junction obstruction demonstrate that: 1) There are multiple distinct histologic patterns, 2) Intraabdominal findings do not predict the histology of the uterotubal junction pathology, 3) Any histologic pattern can be associated with a previous intrauterine or ectopic pregnancy, and 4) The obstruction begins within the transmural portion of the oviduct, extends a variable distance into the isthmic segment, but does not obstruct the ampullary segment. These data suggest that the initiating process originates within the uterus and that fibrosis may represent a nonspecific response to chronic injury of the transmural and isthmic segments of the oviduct.

Chronic Disease↗
PubMed1985

Macrophages and infertility: enhancement of human macrophage-mediated sperm killing by antisperm antibodies.

The mechanism by which antisperm antibodies inhibit fertility is not completely understood. Macrophages may play a role in mediating infertility by interacting with sperm and destroying gametes. Experiments were conducted evaluating the effect of antisperm antibody on the phagocytosis and lysis of sperm by human peritoneal macrophages in vitro. Sperm from a fertile man treated with sera from normal men and women or medium alone had 5 to 280 molecules of IgG/sperm, as determined by a 125I-labeled anti-human IgG monoclonal antibody assay. By contrast, sperm treated with sera containing antisperm antibodies had 310 to 1240 molecules of IgG/sperm. Peritoneal macrophages harvested from infertile women with tubal/adhesive problems mediated phagocytosis and lysis of 111In-labeled sperm which was enhanced by treatment of the sperm with sera containing antisperm antibodies (39.0% +/- 1.5% versus 76.3% +/- 3.2% phagocytosis, and 3.3% +/- 0.3% versus 23.3% +/- 2.3% lysis of sperm [control versus antibody-treated]). The likelihood of fertilization in couples with antisperm antibody may be determined not only by the antibody but also by the presence of genital tract macrophages capable of destroying the antibody-coated sperm.

Agglutination Tests↗
PubMed1985

Unusual mullerian anomalies associated with distal extremity abnormalities.

A 13-year-old girl was evaluated with nonfamilial mullerian anomalies consisting of bilateral blind uterine horns, a separate cervical remnant, and total vaginal agenesis. The observed musculoskeletal abnormalities of the distal extremities differed from those usually associated with both nonfamilial mullerian agenesis (Rokitansky-Küster-Hauser syndrome) and the familial syndromes associated with mullerian anomalies. The pattern of mullerian dysgenesis is unusual in that the entire vagina is absent and a cervical remnant separate from the two blind uterine horns is present in the midline in the normal course of the paramesonephric ducts.

Abnormalities, Multiple↗
PubMed1984

Screening of potential reproductive toxicants by use of porcine granulosa cell cultures.

While approximately 60 000 chemicals are in widespread use with 1000 new chemicals introduced into the environment each year, the biologic effects of these agents are poorly understood. With the specific goal of testing for potential reproductive toxicity, we have established methodology for the screening of compounds in vitro by measuring effects on progesterone production by porcine granulosa cells in culture. Granulosa cells were harvested by mechanical agitation, cryopreserved, and cells with known progesterone production capacity utilized for culture. Agents to be tested were added to cultures of 10(5) cells and the media assayed for progesterone by radioimmunoassay. Estradiol suppression of progesterone production was easily demonstrated in this system and utilized as a verification of responsiveness. The pesticide o,p-DDT and its isomer p,p-DDT produced dramatic suppression of progesterone production apparently with equal potencies to estradiol. By contrast, the pesticides malathion, parathion and dieldrin and the fungicide hexachlorobenzene were without effect in this test system.

Animals↗
PubMed1984

Human peritoneal macrophages possess two populations of IgG Fc receptors.

To characterize the binding properties of the Fc receptors on human macrophages, the binding of radiolabeled human IgG1 to peritoneal macrophages was assessed. Cells were obtained at the time of diagnostic laparoscopy from women undergoing evaluation of infertility. Macrophages bound on the average more IgG1 monomer than monocytes but the avidity with which both types of cells bound IgG1 monomer was comparable. By contrast, macrophages bound much more IgG1 dimers than monocytes. Scatchard plots of the binding of dimer to monocytes were linear, but plots of binding to macrophages were markedly curvilinear. This curvilinearity was not an artifact of extensive ligand internalization or catabolism by cells, since 80% of binding was reversible and there was very little catabolism of ligand in the medium. Assuming that the observed curvilinearity was due to the presence of two independent subpopulations of receptors, an objective estimate for the number of receptors per cell and of the avidity with which each subpopulation bound IgG1 dimer was obtained using a previously described computer program (Scatfit). The analysis of the binding of dimer to macrophages from six donors suggested the presence of 42,000 +/- 33,000 high avidity receptors per cell which bind IgG1 dimer with a mean Ka of 2.7 X 10(9) M-1 and 218,000 +/- 127,000 low avidity receptors which bind the same ligand with a Ka of 1.1 X 10(7) M-1. ADCC of IgG antibody-coated sheep red blood cells mediated by macrophages was less readily inhibited by soluble IgG1 monomer than ADCC mediated by peripheral blood monocytes. This provides further evidence for the presence of low avidity receptors which bind monomeric IgG1 poorly and also suggests that these sites are functionally active in triggering antibody-dependent immune clearance.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

The efficacy of postoperative hydrotubation: a randomized prospective multicenter clinical trial.

Term pregnancies following surgery on patients with distal tubal obstruction have been disappointingly few. There has been continuing interest in whether postoperative hydrotubation increases the rate of pregnancy following salpingoneostomy and fimbrioplasty. This hypothesis was tested in a prospective, randomized, multicenter clinical trial. Patients with no infertility factors other than distal fimbrial disease were randomly assigned to either a control group (no hydrotubation, n = 86) or one of two treatment groups (hydrotubation with lactated Ringer's solution, n = 60, or lactated Ringer's solution containing hydrocortisone, n = 60). The statistical evaluation of differences among treatment groups was based on the Cox Proportional Hazards Model, which allows for covariable adjustment and for the inclusion of all patients regardless of the length of follow-up. A significant difference in the live birth rate could not be demonstrated among the groups studied (P = 0.36). The probability of a successful live birth among women treated by hydrotubation with hydrocortisone was about one-half that of the other groups (P = 0.12). Patients with moderate and severe disease had a substantially lower probability of pregnancy than those with mild disease (P = 0.013 and P = 0.0016, respectively). The probability of pregnancy increased somewhat as the number of previous pregnancies increased (P = 0.12). In this clinical trial, a beneficial effect following postoperative hydrotubation could not be demonstrated.

Adult↗
PubMed1984

Prenatal diethylstilbestrol exposure in the mouse: effects on ovarian histology and steroidogenesis in vitro.

The effect of prenatal diethylstilbestrol (DES) exposure on ovarian morphology and steroid production in vitro was evaluated in the mouse. Pregnant mice were injected with 100 micrograms DES per kg maternal body weight on Days 9 to 16 of gestation and the female offspring sacrificed from 3 to 14 months of age. Ovaries of DES-exposed animals weighed significantly less than controls at 3 months of age (9.4 +/- 0.79 mg vs. 17.54 +/- 0.69 mg, mean +/- SEM). Histologically, the DES animals had an apparent increase in the size of the interstitial compartment with cells showing uniform vacuolization and tubular architecture. In addition, the lipid content of the interstitial compartment, as assessed by oil-red-O staining, was markedly increased in the treated animals as compared to controls and corresponded to the vacuolization. Ovarian steroidogenesis in vitro was determined by excising ovaries of animals from 3 to 14 months of age, placing them in tissue culture for 24 h, and measuring media steroids by radioimmunoassay. Estrogen, progesterone and testosterone production per mg of tissue was increased in DES-exposed animals at all ages studied. To correct for changes in the relative sizes of the ovarian compartments secondary to DES exposure, steroid production was calculated on a "per ovary" basis. Only testosterone production remained elevated "per ovary" in the DES-exposed animals which is consistent with androgens being the primary secretory products of the enlarged interstitial compartment. These data indicate that in the mouse, prenatal DES exposure is associated with an enlargement of the ovarian interstitial compartment, increased lipid content of the individual interstitial cells, and increased interstitial compartment testosterone production in vitro throughout the reproductive life span of the animal.

Animals↗
PubMed1984

Galactorrhea-amenorrhea and hyperprolactinemia associated with pituitary tumors of growth-hormone- and adrenocorticotropic-hormone-secreting cells. A report of two cases.

In women with galactorrhea, amenorrhea/oligomenorrhea, hyperprolactinemia and radiographic evidence of a pituitary tumor, the presumed etiology is usually a primary prolactin-secreting tumor. We treated two patients whose presenting symptoms (galactorrhea and oligomenorrhea) and initial investigation (which showed radiographic enlargement of the sella and hyperprolactinemia) suggested a prolactin-secreting pituitary tumor. However, after further endocrinologic investigation, transsphenoidal exploration and ultrastructural-immunohistologic evaluation of the excised pituitary tumors, the tumors were found to be composed of cells characteristic of growth-hormone and adrenocorticotropic-hormone production. These data are consistent with the hypothesis that any factor or factors increasing intrasellar pressure, including pituitary tumors originating in cells other than galactotrophs, can elevate serum prolactin and present clinically as galactorrhea-amenorrhea. They suggest further that a diligent search be done for elevations of other pituitary trophic hormones when a pituitary tumor is suspected in order not to overlook other kinds of serious endocrinopathy.

Adenoma↗
PubMed1984

Peritoneal fluid prolactin in infertile women with endometriosis: lack of evidence of secretory activity by endometrial implants.

To evaluate the functional status of endometriotic implants, a luteal secretory product of endometrium, PRL, was measured in the PF of 27 infertile women with endometriosis, 13 infertile women without endometriosis, and 11 fertile women undergoing elective sterilization. PF PRL concentrations and PF/plasma PRL ratios were similar in all the groups and did not vary with the menstrual cycle or the stage of endometriosis. These data demonstrate that the ectopic endometrium in infertile women with endometriosis does not secrete PRL in amounts sufficient to elevate PF concentrations and suggest that the infertility observed in these women is probably not dependent upon the secretory activity of endometriotic implants.

Adult↗
PubMed1984

Diverse humoral and cell-mediated effects of antisperm antibodies on reproduction.

No single test to detect the presence of antisperm antibodies has correlated precisely with subsequent fertility. The purpose of this study was to determine whether heterogeneous effects of antibodies could potentially explain this observation. The effects of serum on sperm motility, complement-mediated sperm lysis, mouse macrophage-mediated sperm phagocytosis, and sperm IgG opsonization were assessed in several patients with known antisperm antibodies. Each patient's serum produced its own unique profile. Motility ranged from normal (70% to 85%) to 10% using different subjects' serum. Antibody-dependent complement-mediated sperm lysis ranged from 35% to 65%. Normal sperm incubated with normal serum had approximately 200 molecules of IgG per sperm, whereas normal sperm incubated with patient sera had 546 to 900 molecules of IgG per sperm. In all cases where serum enhanced IgG sperm opsonization, there was enhanced mouse macrophage-mediated phagocytosis of the opsonized sperm (a three- to fourfold increase). These data suggest that antisperm antibodies may affect reproduction by different mechanisms, including direct humoral effects (immunoglobulin and/or complement) and indirect cell-mediated effects (macrophage-mediated sperm phagocytosis). However, the mechanism(s) involved are unique to each individual's antibody. The heterogeneity of these potential mechanisms may explain why the presence of antisperm antibodies as measured by a single assay correlate poorly with infertility.

Agglutination Tests↗
PubMed1983

The outcome of pregnancy in patients with treated and untreated prolactin-secreting pituitary tumors.

Few data document pregnancy risks in patients with prolactin-secreting pituitary tumors, particularly risks relating to the likelihood and severity of increased tumor size. This study presents three groups of women with such lesions. Group 1 consisted of 47 women with transsphenoidal resection who were euprolactinemic postoperatively. Of this group 20 of 22 previously infertile women conceived 25 pregnancies. Group 2 was composed of 17 women who were operated upon but in whom prolactin was still raised (greater than 50 ng/ml) postoperatively and bromocriptine was subsequently used. Seven of these 17 patients were previously infertile, and six of the seven have conceived. In group 3 22 infertile women with small pituitary tumors were not operated upon but received bromocriptine. Eighteen of these patients have achieved 24 pregnancies. Methods of diagnosis, surveillance during pregnancy, and medical and surgical management are presented. Only two patients, both in group 3, developed signs of expanding tumor size in pregnancy.

Female↗
PubMed1983

Developmentally arrested oviduct: a structural and functional defect in mice following prenatal exposure to diethylstilbestrol.

To determine the effects of exposure to diethylstilbestrol (DES) on the developing oviduct, timed pregnant CD-1 mice were treated with DES (10-100 micrograms/kg subcutaneous) on days 9-16 of gestation. Prenatal DES-exposed and age-matched control mice were sacrificed from day 16 of gestation to 15 weeks of age and oviductal development was compared. Following prenatal exposure to DES (100 micrograms/kg), the oviduct at all ages examined was uncoiled and shorter, closely adherent to and wrapped around the ovary in an anatomical configuration similar to the fetal mouse. In addition, the demarcation between the oviduct and uterus was not readily apparent. Histological changes in the DES (100 micrograms/kg) oviduct as compared with control at 10-15 weeks of age included a proliferation of columnar epithelium lining the lumen with gland formation extending into the underlying stroma, absence of or a reduced amount of fimbrial tissue, increased thickness of the muscular wall, and inflammatory cell infiltration. Also, as a functional test of uterotubal junction integrity, Coomassie Blue dye was injected into the uterus. The control uterotubal junction confined the fluid to the uterus. In 80% and 100% of the animals exposed prenatally to DES (10 and 100 micrograms/kg, respectively), independent of the extent of the gross abnormality, the dye readily flowed into the oviduct and filled the ovarian bursa. We conclude that prenatal DES exposure can alter fetal development of the mouse oviduct, resulting in an apparent developmental arrest and functional disruption of the integrity of the uterotubal junction. The fetal like configuration of the ovary, oviduct, and uterus suggests the term developmentally arrested oviduct (DAO).

Abnormalities, Drug-Induced↗
PubMed1983

Macrophages and infertility: oviductal macrophages as potential mediators of infertility.

Human peritoneal macrophages have previously been shown to phagocytize normal sperm. We had hypothesized that if macrophages were present in the distal oviducts, they could interfere with fertilization by phagocytizing sperm in vivo. The present study was designed to determine whether functional macrophages are present in the human oviducts, and to determine the relationship between oviductal and peritoneal macrophages. Forty patients undergoing laparotomy for sterilization or evaluation of infertility or other gynecologic factors were studied. Infertile patients with endometriosis had more peritoneal macrophages than did fertile normal women or infertile women with distal or proximal tubal obstruction. Oviductal macrophages were observed in all patients. The oviductal macrophages were indistinguishable from the peritoneal macrophages, as judged by similar morphologic features, adherence to plastic, phagocytosis of polystyrene spheres and IgG-coated erythrocytes, and presence of peroxidase and alpha-naphthylbutyrate esterase. Patients with endometriosis had the highest numbers of oviductal macrophages, while those patients with distal tubal obstruction had extremely few oviductal macrophages. The results suggest that oviductal macrophages may arise from peritoneal macrophages that migrate into the oviducts.

Adult↗
PubMed1983

Spontaneous tumor cell killing by human blood monocytes and human peritoneal macrophages: lack of alteration by endotoxin or quenchers of reactive oxygen species.

Human mononuclear phagocytes (monocytes and macrophages) act as effectors in the destruction of tumor cells. Peritoneal macrophages from normal or infertile women killed a variety of tumor cells in vitro more efficiently than did blood monocytes from the same subjects. Lysis depended on the effector-to-target cell ratio and was neither reproduced by supernatants from nor lysates of the mononuclear phagocytes. Normal fibroblasts were not lysed. Lipopolysaccharide (10(1)-10(4) ng/ml) did not alter the monocyte- or macrophage-mediated tumor cell killing. The monocytes and macrophages had equivalent basal and phorbol 12,13-myristate acetate-stimulated H2O2 and O-2 production, and the reactive oxygen species scavengers or quenchers catalase, superoxide dismutase, mannitol, and L-histidine did not diminish the killing. These observations suggest that the spontaneous tumor cell killing by human mononuclear phagocytes was not mediated by reactive oxygen species.

Adult↗
PubMed1983

Infertility in women exposed to diethylstilbestrol in utero.

To evaluate the reproductive consequences of prenatal diethylstilbestrol (DES) exposure, 33 infertile couples were studied in whom the female had been exposed to DES in utero. Infertility was attributed to uterotubal junction obstruction in 3 couples, anovulation in 7, endometriosis in 11, cervical obstruction in 2, adnexal adhesions in 2, oligospermia in 1 and luteal insufficiency in 3; in 4 couples no cause of infertility could be identified. No unique intraabdominal abnormalities attributable to DES exposure were observed. Four tubal pregnancies occurred in women with grossly normal oviducts. Nine of 11 women who had previously undergone surgical manipulation of the cervix (cryosurgery, cautery or conization) developed cervical stenosis, and 8 of them were found to have endometriosis. Despite our not having an appropriate referral infertility population for comparison, these findings are consistent with the following hypotheses regarding women prenatally exposed to DES: (1) surgical manipulation of the cervix more frequently leads to cervical stenosis and ultimately pelvic endometriosis, (2) tubal pregnancies may occur by a mechanism unrelated to salpingitis, and (3) the spectrum of problems causing infertility is similar to that in the non-DES-exposed population.

Adult↗
PubMed1982

Sperm phagocytosis by human peritoneal macrophages: a possible cause of infertility in endometriosis.

The mechanism of infertility in women with endometriosis is unknown, but it is independent of mechanical factors that affect fallopian tube function. Increased numbers of peritoneal macrophages are present in women with endometriosis and have access to the female reproductive tract via the oviducts. To determine whether peritoneal macrophages might phagocytize sperm and thereby contribute to infertility in women with endometriosis, we examined peritoneal macrophages from 32 fertile and infertile women; the infertile group was separated into those with and those without visible endometriosis. Peritoneal macrophages from infertile patients with endometriosis phagocytized more normal sperm in vitro (84% +/- 4%) than did those from fertile women (43% +/- 4%) or infertile women without endometriosis (46% +/- 8%) (p less than 0.002). The sperm phagocytosis occurred rapidly and reached a peak by approximately 6 hours. Incubation at 0 degrees C, lysing the macrophages by freezing and thawing, or fixing the macrophages with glutaraldehyde inhibited the sperm uptake by macrophages. The process occurred in cultures with or without serum, thereby indicating that the sperm phagocytosis was not dependent on sperm opsonization with a serum factor. Electron microscopy showed internalization of the spermatozoa into phagosomes with subsequent intravacuolar degradation. These data demonstrate that: (1) peritoneal macrophages phagocytize and degrade sperm in vitro and (2) peritoneal macrophages isolated from women with endometriosis exhibit greater phagocytosis in vitro than do macrophages from fertile women or infertile women without endometriosis. These results suggest that, if peritoneal macrophages from women with endometriosis enter the reproductive tract via the oviducts, they might adversely influence fertilization by phagocytizing sperm.

Adult↗