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Biomedical subjects

N J Alexander

Publications and source records attributed to N J Alexander.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of unilateral injury to the vas deferens on the contralateral testis in immature and adult rats.

The relationship between alterations in testicular histology and antisperm antibodies in immature and mature Lewis rats subjected to unilateral vasectomy was studied. Forty percent of immature rats and 90% of mature rats (p < 0.01) demonstrated significant alterations in both the obstructed (vasectomy) testis and the contralateral testis. There were significant changes in antisperm antibodies (ELISA) in the animals which demonstrated histologic changes.

Age Factors↗
PubMed1994

Defective calcium influx and acrosome reaction (spontaneous and progesterone-induced) in spermatozoa of infertile men with severe teratozoospermia.

OBJECTIVE: To evaluate the acrosome reaction and its prerequisite, a calcium influx, in spermatozoa of infertile men with a high incidence of abnormal sperm forms. DESIGN: Prospective, controlled study. SETTING: Academic tertiary assisted reproduction center. PATIENTS: Patients (n = 14) were allocated in the study after semen evaluation showed teratozoospermia (< 14% normal sperm forms) as diagnosed by strict criteria. INTERVENTIONS: After swim-up separation of the motile fraction, acrosome reactions were evaluated using Pisum sativum agglutinin (both spontaneously and exogenously induced with P and the calcium ionophore A23187, both at 10 microM); the intracellular-free [Ca2+]i was assessed by the fluorescent fura-2 indicator (basal and after P). RESULTS: Patients did not show the typical P-induced wave of [Ca2+]i that was observed in controls but rather a blunted response, no response at all, or abnormal basal [Ca2+]i levels. The percent of basal acrosome reaction was significantly lower for patients versus controls postswim-up, and at 1 hour and 3 hours. Furthermore, there was a significant difference in the response of acrosome reaction to P both at 1 hour and 3 hours, with patients showing almost no response at all. However, patients' acrosome reaction response to the calcium ionophore was similar to those of fertile men. CONCLUSION: Infertile patients with a high incidence of abnormal sperm forms as diagnosed by strict criteria have a low incidence of spontaneous acrosome reaction and a diminished P-stimulated acrosome reaction, whereas the nonspecific response to a calcium ionophore is conserved. Parallel abnormalities of [Ca2+]i were observed in patients, suggesting that these sperm populations may have a defective nongenomic P sperm receptor and/or abnormalities of other membrane transduction systems.

Acrosome↗
PubMed1994

Contraceptive vaccine development.

Recent advances in antigen definition and production have made the development of a contraceptive vaccine more attainable. Such a vaccine must evoke an immune response that blocks an indispensable step in the reproductive process. Vaccine research involves many approaches to fertility prevention. Vaccines are being developed that could interrupt fertility by inhibition of gonadotrophin release, the function of follicle-stimulating hormone or the effects of human chorionic gonadotrophin (hCG); alternatively, they may prevent fertilization by interfering with the transport of spermatozoa or with sperm-zona pellucida binding. The most advanced prototype is a vaccine based on antibodies to beta hCG. Such vaccines are being studied for clinical efficacy. Many hurdles remain in contraceptive vaccine development. Since the antigens are peptides or small proteins, the resultant immune response is usually moderate, and better adjuvants and delivery systems must be developed to enhance and maintain the immune response. Improvement of the mucosal immune response may be necessary for vaccines incorporating sperm antigens. Research on vaccines that control fertility has resulted in a fascinating base of scientific knowledge that, it is hoped, can be converted into products that will allow another option for individuals who wish to control their fertility.

Animals↗
PubMed1994

A sequential analysis of the effect of progesterone on specific sperm functions crucial to fertilization in vitro in infertile patients.

The objective of these studies was to evaluate the modulatory effect(s) of progesterone on sperm functions crucial to fertilization in infertile men with abnormal sperm parameters. A prospective, controlled study applying a sequential diagnostic analysis capable of identifying specific dysfunctions of the male gamete was performed. Patients (n = 14) were allocated to the study group if they had a history of infertility of > 1 year duration and after semen evaluation showed teratozoospermia (< 14% normal sperm forms as diagnosed by strict criteria) or terato-asthenozoospermia (< 50% progressive motility). After swim-up separation of the motile sperm fraction, the following functions were assessed with and without previous exposure to progesterone (1.0 micrograms/ml): acrosome reaction (using Pisum sativum agglutinin), hyperactivated motility (using a computerized semen analyser), sperm-zona pellucida binding (in the hemizona assay), sperm-zona pellucida penetration (in a sperm-zona penetration assay), and sperm-oocyte penetration (using the hamster zona-free oocyte/sperm penetration assay). Progesterone did not affect the percentage of acrosome-reacted spermatozoa after 1 or 3 h of incubation. Hyperactivated motility was significantly enhanced by progesterone after 1 h (12 +/- 4 versus 6 +/- 2% in controls; P < 0.02). Although progesterone did not affect sperm-zona binding, it significantly enhanced both sperm-zona pellucida penetration (27 versus 12% in controls; P = 0.03) and sperm-oocyte penetration (15 versus 8% in controls; P < 0.05). Because those sperm functions enhanced by progesterone are crucial to fertilization, the steroid may have value in the treatment of some male-factor patients undergoing assisted reproductive therapy.

Acrosome↗
PubMed1994

Intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia.

The simian immunodeficiency virus (SIV)-rhesus macaque model of heterosexual human immunodeficiency virus transmission consists of atraumatic application of cell-free SIVmac onto the intact vaginal mucosa of mature female rhesus macaques. This procedure results in systemic infection, and eventually infected animals develop the clinical signs and pathologic changes of simian AIDS. To achieve 100% transmission with the virus stocks used to date, multiple intravaginal inoculations are required. The current titration study utilized two stocks of SIVmac and demonstrated that a single intravaginal dose of cell-free SIV can reliably produce infection in rhesus macaques. This study also demonstrated that some animals intravaginally inoculated with cell-free SIVmac develop transient viremia characterized by a limited ability to isolate virus from peripheral blood mononuclear cells and lymph node mononuclear cells and no seroconversion to SIV antigen. SIV could be isolated from the peripheral lymph nodes of transiently viremic animals only during periods of viremia and not at times when SIV was not detected in circulating mononuclear cells. Thus, peripheral lymphoid tissues were not reservoirs of infection in the transiently viremic animals. Taken together, these results suggest either that the SIV infection was cleared in the transiently viremic animals or that SIV infection is limited to a compartment of the genital mucosal immune system that cannot be assessed by monitoring SIV infection in peripheral blood mononuclear cells and peripheral lymphoid tissue.

Animals↗
PubMed1994

Pathology and localization of simian immunodeficiency virus in the reproductive tract of chronically infected male rhesus macaques.

BACKGROUND: Despite the fact that human immunodeficiency virus (HIV) is transmitted by sexual contact, the biology of this mode of transmission remains largely undefined. HIV is present in semen in both cell-free and cell-associated forms and can be isolated from asymptomatic individuals and AIDS patients. The source of HIV in semen and the target cells for HIV transmission to men are unknown. Epidemiologic studies have shown that in men, the presence of an intact foreskin is associated with increased risk of HIV infection. EXPERIMENTAL DESIGN: The reproductive tracts from 13 chronically simian immunodeficiency virus (SIV)-infected adult male rhesus macaques were examined for this study. Routine histologic examination was undertaken to characterize the reproductive tract pathology. In situ hybridization and immunohistochemistry were used to localize SIV-infected cells and determine the immunophenotype of inflammatory infiltrates. RESULTS: SIV-infected cells (macrophages, T cells) were found at all levels of the reproductive tract and were commonly associated with inflammatory lesions. Infected cells were found most consistently in the epididymis. In one animal, SIV-infected cells (presumably Langerhans cells) were present in the stratified squamous epithelium of the foreskin. Testicular atrophy and degeneration were relatively common findings. The most common lesion in the accessory glands was mild lymphocytic inflammation. In addition, atrophy of the glandular elements and interstitial fibrosis in the prostate gland were found. One animal had a granulomatous epididymitis with multinucleate giant cells that may have been a primary SIV lesion. CONCLUSIONS: The reproductive tract pathology in chronically SIV-infected male rhesus macaques and AIDS patients is similar. SIV-infected cells can be found at all levels of the male rhesus macaque reproductive tract and SIV can infect cells in the mucosal epithelium of the foreskin. This latter finding indicates that target cells for HIV transmission may be present in the foreskin epithelium of uncircumcised men.

Animals↗
PubMed1993

Vasectomy, serum assays, and coronary heart disease symptoms and risk factors.

We compared three serum assays (two antisperm antibody assays and one assay for circulating immune complexes) and a number of CHD-related variables in 69 vasectomized (V) and 126 non-vasectomized (NV) participants in the Portland Center for the Multiple Risk Factor Intervention Trial. Significant differences between the V and NV men were found in sperm agglutination (SA) and sperm immobilization (SI) titers, as well as in several CHD risk factors, symptoms, and treatments; men in the V group had higher titers for SA and SI, smoked more, and had lower diastolic and systolic blood pressure than men in the NV group. Differences between V and NV in SA and SI activity remained even after we controlled for any effects that CHD risk factors, symptoms, and treatments may have had on the serum assays. Antibody development tended to decrease with age-at-vasectomy and increase with time-post-vasectomy. In the case of SA the antibodies clearly increased with time-post-vasectomy.

Adult↗
PubMed1993

Effect of progesterone on human zona pellucida sperm binding and oocyte penetrating capacity.

OBJECTIVE: To determine if sperm exposure to P produces an enhancement in its fertilizing capacity. DESIGN: Sperm from fertile donors were exposed to P at 0.1 and 1.0 microgram/mL for 1 or 24 hours. The effects on hyperactivated (HA) motility at 1 and 4 hours, acrosome reaction (as determined by Pisum sativum agglutinin or T6/antibody techniques), on human zona pellucida binding (by using the hemizona assay), and on the penetrating ability (by using the zona-free hamster ova assay) were evaluated. RESULTS: Exposure to P at 1.0 microgram/mL enhanced HA motility after 1 and 4 hours of P exposure, the acrosome reaction after 24 hours' incubation, the number of sperm bound/hemizona after 1-hour incubation, and the penetration rates in the hamster ova assay at both incubation intervals. CONCLUSION: Sperm exposure to P enhances its fertilizing capacity in fertile men, and further investigation is warranted as a possible treatment for male factor patients.

Acrosome↗
PubMed1993

Prevention of sexually transmitted infections. Physical and chemical barrier methods.

Barrier contraceptives, including mechanical methods, chemical methods, and combinations thereof, have the potential to decrease the spread of STDs, are inexpensive, and do not have any systemic effects. Currently, the concerns that the efficacy of latex condoms is limited because they are not consistently used, they can break, may cause allergies, and have a limited shelf-life has led to the development of condoms made of other materials such as polyurethane. Spermicides using nonoxynol-9 as their active ingredient have been shown to be effective in preventing the transmission of some STDs such as gonorrhea and chlamydia. In the absence of well-controlled studies of nonoxynol-9 efficacy against HIV, questions have been raised that some formulations, high doses, or frequent use may be associated with genital tract irritation, and possibly, enhancement of HIV transmission. Because heterosexual transmission will continue to be the major route of HIV transmission worldwide, the development and consistent use of a chemical or mechanical barrier during intercourse may be the best way to decrease the spread of HIV.

Condoms↗
PubMed1993

Adenocarcinoma of renal pelvis.

Adenocarcinoma accounts for a small percentage of neoplasms arising within the renal pelvis. We describe a mucinous adenocarcinoma of the renal pelvis that occurred in a 57-year-old woman. Investigation of the recent literature reveals an additional 12 cases of adenocarcinoma of the renal pelvis reported since 1980. These 13 cases are summarized in detail, for a total of 59 cases of adenocarcinoma of the renal pelvis documented in the English-language literature. These tumors can be subdivided into three major histologic types: tubulovillous, mucinous, and papillary non-intestinal. The tubulovillous and mucinous tumors are morphologically similar to intestinal tumors accounting for 71.5% and 21.5% of cases, respectively. They are believed to arise in foci of intestinal metaplasia. Only three cases (7%) were of the nonintestinal, nonmucinous, papillary subtype. These rare tumors are notable for their morphologic similarity to Bellini or collecting duct carcinoma, but a specific morphologic precursor has not been identified. Of the three subtypes, tumors of tubulovillous morphology confer the worst prognosis with 70% of patients dying within 5 years. Thirty-three percent of mucinous tumors and none of the papillary nonintestinal tumors were fatal.

Adenocarcinoma↗
PubMed1993

Effects of sperm-immobilizing antibodies on sperm-zona pellucida tight binding.

OBJECTIVE: To evaluate the in vitro effects of sperm-immobilizing antibodies on sperm-zona pellucida (ZP) tight binding. DESIGN: The hemizona assay (HZA) was used to study the inhibitory effects of infertile women's sera with and without sperm-immobilizing antibodies on sperm ZP tight binding. These results were compared with those of monoclonal sperm-immobilizing antibodies. SETTING: The patients were collected from a university hospital infertility clinic. PATIENTS: Sera from 40 infertile women (24 with and 16 without sperm-immobilizing antibodies) and 2 postpartum women as control were used. RESULTS: Of 24 patients' sera with sperm-immobilizing antibodies, 23 (96%) showed significant inhibitory effect, whereas none of 16 patient's sera without sperm-immobilizing antibodies exhibited any inhibitory effect. However, there was no correlation between the antibody titers of sperm-immobilizing antibody and the hemizona index. Among four monoclonal sperm-immobilizing antibodies tested, only one showed a significant inhibitory effect on the sperm-zona tight binding. A human monoclonal antibody derived from an infertile woman with sperm-immobilizing antibodies, whose serum showed an inhibitory effect on HZA, did not inhibit the HZA. CONCLUSIONS: There are at least two kinds of sperm-immobilizing antibodies, one with both activities of sperm immobilization and blocking of sperm-zona tight binding and another with the former activity alone. The vast majority of sperm-immobilizing antibodies reduce zona binding even without the presence of complement.

Animals↗
PubMed1992

The effect of contraceptives containing nonoxynol-9 on the genital transmission of simian immunodeficiency virus in rhesus macaques.

The ability of two nonoxynol-9 spermicide preparations to prevent the genital transmission of SIV in rhesus macaques was compared. Administration of one mL of contraceptive foam before the intravaginal inoculation of cell-free SIV prevented the genital transmission of SIV to three of six animals, and using one mL of contraceptive gel prevented the genital transmission of SIV to two of six animals. Thus, both contraceptive foams and gels containing nonoxynol-9 provided protection against the genital transmission of SIV.

Animals↗
PubMed1992

Localization of SIV in the genital tract of chronically infected female rhesus macaques.

Despite the fact that human immunodeficiency virus (HIV) is transmitted primarily by sexual contact, the biology of the sexual transmission of HIV is poorly understood. Simian immunodeficiency virus (SIV) can be transmitted to female rhesus macaques by placing cell-free virus into the vaginal canal, and SIV can be isolated from the vaginal secretions of infected rhesus macaques. The authors examined the genital tracts from 16 chronically infected female rhesus macaques and localized SIV-infected cells using in situ hybridization and immunohistochemistry. SIV-infected cells were found in the genital tract of 13 of the 16 animals examined, and in most cases the SIV-infected cells were located in the submucosa of the cervix and vagina. However, SIV-infected cells were also found in the vaginal epithelium. SIV-infected cells were more common in sites of inflammation than in normal areas. These findings suggest that SIV gains access to genital tract secretions from the cervix and vaginal epithelium.

Animals↗
PubMed1991

Transforming growth factor-alpha augments meiotic maturation of cumulus cell-enclosed mouse oocytes.

Growth factors have been shown to play an important role in the regulation of ovarian function. In this study, we examined the effects of transforming growth factor-alpha (TGF-alpha) on the meiotic maturation of immature mouse oocytes in vitro. Cumulus cell-enclosed oocytes were exposed to TGF-alpha with or without the meiotic inhibitor hypoxanthine (HX), and oocyte maturation was assessed by germinal vesicle breakdown (GVBD). Likewise, mechanically denuded oocytes were examined for GVBD following exposure to HX and TGF-alpha. When cumulus cell-enclosed oocytes were exposed to TGF-alpha (1 microgram/ml) in the presence of HX (4 mM), an increase in GVBD was observed first after 5 hours of culture. Maximal stimulation was reached at 24 hours when 70% of the oocytes underwent maturation in the presence of TGF-alpha and HX as compared to 33% with HX only. Concentrations of TGF-alpha as low as 0.1 ng/ml produced a similar stimulatory response after 24 hours of culture. Spontaneous maturation in the presence of TGF-alpha, but without HX, was also enhanced. The stimulation of GVBD by TGF-alpha showed an increase over time both with and without HX. When denuded oocytes were exposed to TGF-alpha in the presence of HX, no effect was observed. Our results suggest that TGF-alpha is a potent stimulator of mouse oocyte maturation in vitro and that its effect is mediated by the surrounding cumulus cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antisperm antibodies to sperm surface antigens in women with genital tract infection.

Antisperm antibodies to sperm surface antigens in nulligravid women with primary upper genital tract infections were measured by the sperm mixed agglutination reaction assay. As many as 56% of women with a primary episode of pelvic inflammatory disease had antisperm antibodies. In addition, 69% of those women with no history of genital tract infection but with laparoscopic evidence of past pelvic infection had significant levels of circulating antisperm antibodies. Electroimmunoblots of sperm preparations probed with the sera of women who had either known or presumed upper genital tract infection revealed a uniformly recognized 69 kd antigen. In contrast, women with circulating antisperm antibodies before primary upper genital tract infection recognized up to five distinct sperm antigen determinants of 27, 54, 131, 146, and 174 kd. It is a distinct possibility that genital tract infections may lead to immunopotentiation of antisperm antibodies that could affect fertility.

Adolescent↗
PubMed1991

Evaluation of human sperm-zona pellucida tight binding by presence of monoclonal antibodies to sperm antigens.

Characterized WHO monoclonal antibodies (MAbs) to human sperm antigens were evaluated as to whether they inhibited sperm-zona pellucida tight binding as assessed by the hemizona assay (HZA). Of the 26 MAbs tested, only one inhibited zona binding. The whole sperm-specific MAb inhibited zona binding by 70%. The MAb also caused strong agglutination. Two procedures, Sephadex column chromatography and papain digestion, were used to determine whether agglutination or steric hindrance was a factor in the capability of MAb to inhibit zona binding. However, inhibition remained comparable to previous results. The MAb did not prevent capacitation, nor calcium influx and the resulting increase in hyperactivated motility and acrosome reaction. Since its inhibitory influence is not due to agglutination factors, steric hindrance or prevention of normal pre-fertilization maturation, the MAb may be blocking a portion of the zona binding receptor and may be useful in elucidating sperm antigens important to sperm-egg interaction. The approach used in this study allows definition of sperm surface antigens involved in zona pellucida binding.

Antibodies, Monoclonal↗