Search PubMed⌕ Search

Biomedical subjects

N J Alexander

Publications and source records attributed to N J Alexander.

At least 91 records · Page 5Linked to original sources
PubMed1986

Diet and vasectomy: effects on atherogenesis in cynomolgus macaques.

We report here the effect of a moderately atherogenic diet on the progression of atherosclerosis among cynomolgus macaques that were either vasectomized or sham vasectomized. Both groups were compared to sham vasectomized monkeys fed a control Monkey Chow diet. As expected, slight hyperlipoproteinemia induced by the moderately atherogenic diet increased endothelial cell replication rates and resulted in the development of intimal lesions among sham vasectomized monkeys. Unexpectedly, vasectomy resulted in reduced leukocyte adherence to arterial surfaces, reduced endothelial cell replication rates in response to the moderately atherogenic diet, and at most arterial sites, smaller intimal lesions were produced. These data suggest that with slight hyperlipoproteinemia vasectomy may result in a small protective effect against atherosclerosis, while other studies have shown that marked hyperlipoproteinemia in cynomolgus macaques along with vasectomy results in exacerbation of atherogenesis.

Animals↗
PubMed1986

In vitro cell-mediated and complement-mediated cytotoxicity to murine testicular cells.

Male BALB/c mice at 8 to 14 weeks of age were divided into three groups: group 1 was immunized with an emulsion of testicular cells (TCs) (10(7)/mouse), complete Freund's adjuvant (CFA), and extract of Bordetella pertussis (BP); group 2 was given CFA and BP injections; and group 3 was given sterile saline injections. Suspensions of TCs and spleen cells (SCs) from each mouse were prepared 4 weeks after the first immunization for a cytotoxic T lymphocyte (CTL) assay. For the antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent complement-mediated cytotoxicity (ACC) assays, TCs and SCs were prepared from normal male and female mice, respectively. Targets were labeled with Na251 Cr0(4). The interactions of targets (TCs) and effectors (SCs) were conducted at 32.5 degrees C (for CTL, ADCC, and ACC assays) or 37 degrees C (for ACC assay). In the CTL assay, SCs from group 1 and group 2 caused significantly more killing than those from group 3. Specific cytotoxicity in the ADCC assay was only detected in the serum (maximum specific lysis 47.65%) of one mouse. No other cytotoxicity was detectable in 61 serum samples from group 1 (n = 25), group 2 (n = 17), and group 3 (n = 19). In the ACC assay, no significant specific cytolysis was found at different incubation temperatures (32.5 and 37.0 degrees C) in 44 serum samples from the three groups. These results suggest that CTLs are important in the pathogenesis of experimental allergic orchitis (EAO). Adjuvant alone, probably because of breakdown of the blood-testis barrier, causes significant T lymphocyte cytotoxicity to TCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1986

Antisperm antibodies and circulating immune complexes of vasectomized men with and without coronary events.

We compared antisperm antibody and circulating immune complex (CIC) levels in serum samples from 101 vasectomized and 101 normal age-matched nonvasectomized men; 31 of each group had histories of coronary heart disease (CHD). Vasectomy and CHD status were treated as categorical independent variables in the two-way analysis of variance. Elevations of both systolic and diastolic blood pressures were significantly associated with age and body mass index but not vasectomy. Antisperm antibodies (immobilizing and agglutinating) were significantly associated with vasectomy (P less than or equal to .001); the incidences were similar in men with and without CHD. The CICs were significantly associated with vasectomy in a Staphylococcus aureus (FcSa) CIC assay (P less than or equal to .001) and a Raji cell CIC assay (P less than or equal to .05). A third CIC assay, the Clq binding assay, did not reveal a difference between any subgroups. Generally, CICs occurred more frequently in the CHD group by the FcSa assay and particularly the Raji cell assay (P less than or equal to .001). In summary, vasectomized men had a higher incidence and higher levels of circulating antisperm autoantibodies and CICs than did age-matched controls.

Antigen-Antibody Complex↗
PubMed1985

Reactivity of anti-human sperm monoclonal antibodies with normal placenta, hydatidiform mole, and gestational choriocarcinoma.

The current study was undertaken to examine reactivity patterns of well-characterized anti-human sperm monoclonal antibodies with normal placenta, complete hydatidiform mole (HM), and gestational choriocarcinoma (CCA). Two anti-human sperm monoclonal antibodies (MA2 and MA7) out of a panel of 14 reacted with human CCA cell lines but did not react with the trophoblast of 4 HM or 4 normal placentas from 13 weeks to term gestation in immunofluorescence and absorption tests. Therefore, in terms of expressing these sperm-embryonic antigens, the trophoblast of HM is more like normal placental trophoblast than CCA. The relationships among normal placenta, HM, and CCA may be better understood by continued studies on the pattern of expression of additional embryonic antigens in these three gestational tissues.

Antibodies, Monoclonal↗
PubMed1985

Circulating immune complexes in cynomolgus macaques.

Nonhuman primates can be used as models for the study of immune-complex-associated diseases. Recognizing that very little is known about the levels of circulating immune complexes (CICs) in normal monkeys, we have used three assays to measure the levels in serum collected from 313 adult and 106 juvenile cynomolgus macaques (Macaca fascicularis). The prevalence was higher than expected. There was a strong statistical association between CIC levels and country of origin. Monkeys from Indonesia were more likely to have elevated CICs than those from Malaya or the Philippines. This relationship was observed with all three assays. Furthermore, juvenile macaques tended to have lower levels than did adults. This study indicates that it may be important to consider genetic factors, the country of origin, or both when selecting cynomolgus macaques for research on immune-complex-associated diseases.

Age Factors↗
PubMed1984

Monoclonal antibody to a human germ cell membrane glycoprotein that inhibits fertilization.

A monoclonal antibody to an antigen in the human germ cell membrane did not agglutinate or immobilize sperm but inhibited binding and penetration of zona-free hamster ova by human sperm and blocked murine fertilization in vitro. The antibody, of the 2a subclass of immunoglobulin G, was germ cell-specific but not species-specific. It recognized a single antigen of 23 kilodaltons that has been isolated from human germ cells. This fertilization antigen, located on the postacrosome , midpiece, and tail of human sperm, is a glycoprotein of testicular origin associated with some types of human involuntary immunoinfertility .

Animals↗
PubMed1984

Isolation of a sperm autoantigen from the kidneys of vasectomized rabbits.

The rabbit sperm membrane autoantigen, RSA-1, has been isolated from the kidneys of bilaterally vasectomized rabbits. Using detergent extraction the IgG-RSA-1 complex in the kidney was isolated first on an anti-IgG immunocolumn. The eluted IgG-RSA-1 complex was then applied to an anti-sperm autoantibody column which bound the RSA-1, displacing the kidney anti-RSA-1 IgG. RSA-1 was subsequently eluted from the anti-sperm autoantibody column. This is the first identification of a known sperm antigen in the kidneys of vasectomized animals. Furthermore, this methodology should be applicable to the isolation of antigens from a variety of other tissues and immune complexes.

Animals↗
PubMed1984

Genetic control of humoral immunity to sperm acrosomal and cell surface antigens.

We have defined the nature of genetic control of humoral immunity to sperm cell surface (TSDA) and acrosome (Ac) antigens. A sperm immunization dose that distinguishes between high-responder (BALB/c) and low-responder (B10) strains of mice was identified. B10 mice were unresponsive, whereas BALB/c and F1 hybrid mice responded to sperm of both parental strains. The ratio of nonresponder to responder mice in the B10 X F1 backcross and F1 X F1 inbred generations indicates anti-TSDA or anti-Ac antibody responsiveness is controlled through more than a single gene. The significant correlation found between the anti-TSDA and anti-Ac responses is consistent with the possibility that one or more genes controls antibody responsiveness against determinants common to both the Ac and sperm cell surface. Neither anti-TSDA nor anti-Ac antibody responses were linked to the I-A subregion of the responder H-2d MHC haplotype. In addition to a genetic difference in the control of humoral immunity to sperm, a difference in sperm immunogenicity among strains was observed. Antigens of the Ac of B10 sperm are more immunogenic than those of BALB/c sperm, and this trait is linked to the B10 Y chromosome.

Acrosome↗
PubMed1984

An immunosorption assay for antibodies to spermatozoa: comparison with agglutination and immobilization tests.

We have developed an enzyme-linked immunosorption assay (ELISA) with an antigen extract made by treatment of freeze-thawed sperm pools with 0.3 M lithium 3,5-diiodosalicylate (LIS). This procedure is quick, safe, and simple to perform in a clinical laboratory. When the LIS antigen preparation was compared by ELISA with whole sperm and several other antigen extracts, it was found to be superior in detecting human antisperm antibodies related to infertility; it gave less variability, better precision, and fewer false-positive reactions than whole sperm fixed to the wells as antigen. The antigen was stable when stored at -20 degrees C. In one experimental series, serum samples from 18 normal control subjects and 159 infertility patients with positive sperm-immobilizing titers, positive sperm-agglutinating titers, or both, were tested by ELISA with LIS antigen; the correlation yielded a P less than or equal to 0.0001. Based on another series of 156 samples from patients with positive antibody titers by the sperm agglutination test and 30 sera from normal humans, the predictive value of the test was 96%. In a third series of 162 serum samples obtained from 82 women and 80 men, we found no difference in the test results based on sex. The assay is specific for the antibody binding portion of the immunoglobulin. Absorption of positive sera with sperm but not red blood cells markedly reduces the response. In addition to being more efficient and precise than standard methods, the ELISA eliminates the need for fresh sperm and provides data that can be objectively interpreted.

Antibodies↗
PubMed1984

Interspecies cross-reactivity of monoclonal antibodies directed against human sperm antigens.

Monoclonal antihuman sperm antibodies were used to study the surface antigens of sperm from man, monkey (Macaca mulatta), dog, rabbit, bull and mouse. Quantitative absorption results indicate some of the antibodies cross-react with sperm of all the species tested while three recognized determinants were unique to the human sperm. These reactions were sperm-specific since no cross-reactivity was observed with somatic tissue from human and mouse. In the indirect immunofluorescence test, monoclonal antibodies MA1 and MA4 recognize antigenic determinants which appear within the mouse testis during spermatogenesis and are present on the acrosome and mid-piece sperm regions, respectively, of the species tested. MA2 reacted diffusely with the acrosome of human and monkey sperm only. In contrast, MA3 had a speckled acrosomal staining pattern reacting only with human sperm. Antibodies MA5 and MA6 were also specific for human sperm, binding to the equatorial and tail regions. Live human and monkey sperm were agglutinated and immobilized by MA1 but only immobilized by MA2 . With the Western blot technique, human sperm antigens of approximately 84,000, 240,000, 30,000 and 71,000 daltons were identified by antibodies MA1 , MA3 , MA4 and MA5 , respectively. An acrosomal antigen of approximately 82,000 daltons present on both bull and mouse sperm was identified by MA1 . Antibody MA4 , in turn, identified at 28,000-dalton mouse sperm antigen and a 35,000- to 37,000-dalton antigen present on the midpiece of bull sperm.

Animals↗
PubMed1984

Antibodies to human spermatozoa impede sperm penetration of cervical mucus or hamster eggs.

Antisperm antibodies from infertile patients and men with vasectomies can impede human sperm penetration of hamster eggs. When human spermatozoa were exposed to antisperm antibodies, six samples totally blocked and another ten significantly reduced sperm penetration, and only two samples yielded results comparable with those obtained with normal serum. The penetration rate was 59% for the control sera; the test serum rate was 15%. Ninety percent caused a reduction in egg penetration. The IgG fraction caused a reduction similar to that of whole serum. Antisperm antibodies can also reduce sperm penetration of cervical mucus. We found that 21% of the serum samples reduced mucus penetration. No specific antisperm antibody type (agglutination, immobilization, or antibodies as revealed by immunofluorescence) always prevented cervical mucus penetration or sperm penetration of hamster eggs. Furthermore, exposure to even high titers of antibodies in some serum samples did not result in total prevention of sperm penetration either of hamster eggs or cervical mucus, an indication that only certain antibody types prevent chances of fertility. The use of sperm penetration assays may be valuable tools with which to determine (1) the fertilizability of semen from men who exhibit seminal antisperm antibodies and (2) the importance of various antibodies in the prevention of fertilization.

Animals↗
PubMed1984

Sex selection by sperm separation and insemination.

The Ericsson albumin filtration technique was used to collect a fraction rich in Y sperm for selective insemination in couples desiring a male infant. Of 35 conceptions in which sex was known at delivery or spontaneous abortion, there were 28 males (80%). Twelve pregnancies were achieved after separation of sperm in a Sephadex gel filtration system designed to allow for collection of a fraction enriched in X sperm. Seven pregnancies have resulted in females, two in males, and one in twins of each sex. One patient aborted, and one is still pregnant. While selection for either sex can be done electively, on the basis of sociologic preference, female selection has, as an additional indication, avoidance of male offspring to carriers of sex-linked diseases.

Adult↗
PubMed1984

Hamster egg penetration: comparison of preincubation periods.

Seven-hour and 20-hour incubation periods were tested with donor specimens to be used in the hamster egg sperm penetration assay (SPA). Aliquots of the washed sperm were incubated in air and in 5% CO2 and 95% air at 37 degrees C for comparison of sperm survival rates. The mean penetration for the donors ranged from 0% to 64%, with group means of 21% and 36% for the 7- and 20-hour incubations, respectively. All donors had penetration rates in the fertile range after 20 hours of incubation, but 33% (3 of 9) had penetration rates less than 10% after 7 hours of incubation. Incubation of sperm in air reduced the motility by 9% after 20 hours. The results suggest that the 20-hour incubation in 5% CO2 is better because it reduces the possibility of false-negative results in the SPA. We conclude that penetration in the questionable range of 10% may require further SPA testing with different incubation periods and technique modifications, such as a sperm rise step to increase sperm motility and reduce the number of leukocytes.

Animals↗
PubMed1984

Circulating immune complexes and sperm antibodies following vasectomy in Austrian men.

The incidence of circulating immune complexes (CICs) following vasectomy in men and the timing of their appearance and disappearance remain unsettled. A prospective study was initiated to measure CICs and sperm antibody formation in 44 Austrian men undergoing a vasectomy. Using the Raji cell assay, the incidence of CICs was 11% (5 of 44) prior to surgery, 24% (10 of 42) at 2-3 months, 10% (1 of 10) at 4-6 months and 0% (0 of 23) at 15-26 months following surgery. The incidence of sperm antibodies, employing a sperm agglutination assay and an enzyme-linked immunosorbent assay, was 7% (3 of 44), 17% (9 of 52), 25% (3 of 12) and 27% (3 of 11), at 0, 2-6, 15-20 and 21-26 months following vasectomy, respectively. CICs and sperm antibody levels were not correlated at any time point. These results support previous studies indicating a transient increase in the incidence of CICs, detectable by the Raji cell assay, only at early times following vasectomy.

Antigen-Antibody Complex↗
PubMed1983

Immunologic considerations before and after vasovasostomy.

A prospective study has been completed to determine the incidence and significance of antisperm antibodies in 160 men undergoing vasovasostomy to relieve obstruction of the vas deferens due to vasectomy. Preoperatively, serum sperm-agglutinating antibody (SSAA), serum sperm-immobilizing antibody (SSIA), and seminal plasma sperm-agglutinating antibody (SPSAA) were found in 63%, 37%, and 3%, respectively. When they were postoperatively studied, 92 of the same men demonstrated no significant change in the incidence or the absolute level of SSAA or SSIA. The SPSAA was found in 7% of 120 men preoperatively; however, 16% of 51 men studied postoperatively exhibited SPSAA. Significant differences in pregnancy rates have been documented between the spouses of men with detectable levels of agglutinating and immobilizing antibody and the spouses of men with no evidence of antibody formation.

Autoantibodies↗