Search PubMed⌕ Search

Biomedical subjects

N J Alexander

Publications and source records attributed to N J Alexander.

At least 109 records · Page 6Linked to original sources
PubMed1983

Pregnancy rates in patients treated for antisperm antibodies with prednisone.

Circulating antisperm antibodies are associated with decreased fertility in both men and women. Several recent reports suggest that corticosteroids suppress antibody levels and thus enhance fertility in such patients. Prednisone was given to 24 patients; 26 patients with antibodies were not so treated and served as controls. The treated group comprised five women and 19 men; the control group comprised one woman and 25 men who had equivalent levels of circulating antibodies. The drug, when given to men, did not cause changes in sperm count, motility, or normal forms, but it did cause significant reductions in levels of circulating immobilizing (P less than or equal to 0.039) and agglutinating (P less than or equal to 0.001) antisperm antibodies in both sexes. Fourteen pregnancies occurred during the 4-month posttreatment study period. Significantly more pregnancies occurred in the treated group than in the control group (11 treated patients [45%] and three controls [12%]; P less than or equal to 0.025). Of the five treated women, four conceived.

Antibodies↗
PubMed1983

Spontaneous tumors in long-term--vasectomized mice. Increased incidence and association with antisperm immunity.

In two independent studies the authors have observed a significantly higher incidence of spontaneous tumors in vasectomized BDF1 mice over the long term than in age-matched sham-vasectomized control mice. In the first study, necropsies were performed on the animals at 30 months of age (27 months after surgery), and 15 of 24 vasectomized versus 2 of 14 sham-vasectomized mice (P less than or equal to 0.025) had detectable tumors in various tissues. In a second study, necropsies were performed on the animals at a younger age (18 months, 15 months after surgery), and liver tumors predominated: 82 of 171 vasectomized versus 33 of 97 controls (48% versus 34%, P less than or equal to 0.037) had at least one hepatic tumor, and a significantly higher percentage of vasectomized animals had large (greater than or equal to 31 sq mm) hepatic tumor burdens (80% versus 49%; P less than or equal to 0.002) and multiple hepatic tumors (19% versus 5%; P less than or equal to 0.002). In combined data from both studies, the vasectomy group had a higher incidence of (1) at least one tumor (P less than or equal to 0.025), (2) multiple tumors (P less than or equal to 0.005), and (3) more than one type of tumor (P less than or equal to 0.05. Furthermore, in both studies tumor number and size were significantly associated with antisperm immunity detected by antibody or aspermatogenesis evaluation. It is speculated that sperm degradation products and/or the autoimmune response to sperm that commonly accompanies vasectomy may affect tumor induction or growth directly or indirectly by interfering with immunosurveillance mechanisms.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1983

Gender after artificial induction of ovulation and artificial insemination.

Several studies on artificial insemination by donor (AID) semen have suggested that the gender of infants can be influenced by treatment of the women with clomiphene citrate (CC) and by the type of semen used (fresh versus cryopreserved). We conducted a 3-year prospective clinical trial to test these hypotheses. Two groups of pregnant women were evaluated. Group I (n = 130) comprised women whose ovulation was induced by CC; group II (n = 190) comprised those who conceived during spontaneous ovulatory cycles. In a total of 320 pregnancies, 55 spontaneous abortions occurred, 23.1% in group I and 13.2% in group II (P less than or equal to 0.05). Two tubal ectopic pregnancies occurred in group I. Of the 100 and 165 pregnancies carried to term in the treated and control groups, respectively, 11% and 1.8% involved twins (P less than or equal to 0.005). When only single births were considered, group I had 46.1% males in 89 term pregnancies, and group II had 60.5% males in 162 term pregnancies. Significantly more female offspring occurred in the group treated with CC (P less than or equal to 0.05). Because it is possible that a portion of the effects observed in this study were a function of cryopreservation of the AID semen, we compared data on frozen sperm with data on fresh sperm in terms of abortion, gender, and incidence of multiple births; there were no significant differences. Fertil Steril 40:481, 1983.

Clomiphene↗
PubMed1983

Antisperm antibodies in mouse vasectomy sera react with embryonal teratocarcinoma.

Sera from vasectomized BDF1 mice were tested by immunofluorescence and radioimmunoassay for antibodies reacting with sperm and the mouse teratocarcinoma cell lines F9 and PYS. Antibody titers to both sperm and F9 cells increased with time after vasectomy and were highest in long-term (15 to 30 mo) vasectomized animals. By immunofluorescence assay, 35% of long-term vs 10% of age-matched control mice had antisperm antibodies (p less than or equal to 0.01), 54% of vasectomized vs 21% of controls had antibodies reacting with F9 teratocarcinoma (p less than or equal to 0.01), and 5% of vasectomized vs no controls reacted to the PYS teratocarcinoma cell line. No sera from either group reacted with thymocytes or cultured fibroblasts from male 129/Sv mice (negative somatic cell controls). Kendall's rank order statistical correlation test showed a significant association (p less than or equal to 0.01) between individual responses to sperm and F9 cells. Absorption of positive sera with sperm removed both sperm and F9 reactivity, indicating that the F9 cell-reactive antibodies in vasectomy sera are directed against identical or immunologically cross-reactive antigens present on the surface of sperm and F9 embryonal teratocarcinoma. A combination of electrophoresis and nitrocellulose blotting techniques (Western blot analysis) revealed that sera from some vasectomized mice contain IgG antibodies that react with 50,000 and 150,000 dalton (approximately) antigen bands present in sperm and F9 extracts, but not in PYS or thymocyte extracts. It remains to be determined whether the teratocarcinoma antigens detected in this study are true embryonic antigens or germinal antigens (the F9 cell line may have originated from primordial germ cells in transplanted embryonic tissue). In either case, teratocarcinoma cell lines provide an abundant source of material for the further characterization of these autoantigenic molecules.

Absorption↗
PubMed1982

Possible mechanisms of vasectomy-exacerbated atherosclerosis.

Our laboratory as well as those of others have demonstrated that in experimental animals vasectomy results in immune-complex deposition not only in the reproductive tract but also in the renal glomerulus. We have shown that in two species of monkeys vasectomy results in a significant increase in atherosclerosis and have postulated that this may be due to circulating immune complexes. We have shown a mild change in arteriolar vessels in a small study of vasectomized men and have found a mild but insignificant increase in systolic blood pressure in vasectomized men over time compared to an age-matched group. One cannot ignore the fact that persistent autoimmune responses to spermatozoal antigens are generated in both vasectomized men and animals. The paucity of direct information about whether vasectomy exacerbates atherosclerosis in human subjects has made reliance on animal studies unavoidable. But to date there is no evidence that vasectomy causes a similar effect in human beings.

Animals↗
PubMed1982

Immunity to tumor-associated antigens in vasectomized men.

Leukocytes from 49 vasectomized and 57 age-matched nonvasectomized men were tested in the leukocyte adherence inhibition (LAI) assay for reactivity to sperm and various 3-M KCl human tumor extracts. Forty-four percent of the vasectomized men and 15% of the control group were reactive to the sperm antigen preparation (P less than or equal to 0.03). Similarly, a significantly higher percentage of vasectomized men responded to 3 of 5 tumor extracts tested: melanoma I (34.7 vs. 15.8%, P less than or equal to 0.04), squamous cell carcinoma (48.8 vs. 26.0%, P less than or equal to 0.04), and breast carcinoma (19.5 vs. 4%, P less than or equal to 0.04). Thirty percent of vasectomized versus 4% of the control group responded to more than two tumor antigens (P less than or equal to 0.03). The degree of LAI reactivity to each tumor extract was highly correlated with degree of antisperm LAI reactivity, and the degree of LAI responsiveness to one of the melanoma extracts was significantly correlated with antisperm antibody titer as measured by the sperm-immobilization assay. Furthermore, nonresponsive leukocytes from the control population converted to tumor antigen-responsive when incubated with sera from vasectomized LaI-positive men. Data from this study indicated that a large percentage of vasectomized men with sperm immunity were responsive to tumor-associated antigens in the LAI test and that antisperm antibodies or other serum factors played a role in this response. These results and the evidence that most tumor antigen-responsive cancer patients also have serum antibodies that reacted with sperm suggested that vasectomized men and cancer patients frequently responded to immunologically cross-reactive antigenic determinants present on both sperm and tumor cells.

Antibodies↗
PubMed1982

Effects on the efferent ducts in Macaca mulatta.

Immunopathologic findings in efferent ducts of 36 rhesus macaques vasectomized as many as 12 years earlier and of 11 age-matched control animals were compared. Electron-microscopic observation of these ducts revealed changes after vasectomy. The epithelium shortened from a prevasectomy height of 25 mu to 14 mu as the ducts stretched after vasectomy. The number of sperm and macrophages in the lumen increased. The basement membrane was 300-700 A wide in nonvasectomized animals but several times that in animals vasectomized 6 or more years before; the mean width significantly increased with time after vasectomy. Numerous electron-dense immune complexes were found within the thickened lamina in 33% of vasectomized animals and in none of the controls. The mean size of the electron-dense areas varied from 0.01 sq mu in a monkey vasectomized 3 years earlier to 0.18 sq mu in an animal vasectomized 7 years earlier; the mean area significantly increased with time after vasectomy. Frozen sections of testis and epididymis were evaluated through the use of fluorescein-conjugated antibodies. Of the nonvasectomized controls, 18% showed immune deposits. Of the vasectomized animals, 53% revealed C3 deposition in the basement membrane surrounding the efferent ducts. The presence of electron-dense deposits plus the finding of putative immune complexes as revealed by immunofluorescence suggested that vasectomy enhances leakage of sperm antigens, particularly in the region of the efferent duct.

Animals↗
PubMed1981

Regulatory interactions between mitochondrial genes: interactions between two mosaic genes.

We have studied the mitochondrial DNA and the phenotypes of strains of Saccharomyces cerevisiae with specific intervening sequences in two mosaic genes: cob (the gene for apocytochrome b) and oxi3 (the gene for subunit I of cytochrome oxidase). The results suggest the following. (i) The presence of an intervening sequence downstream encompassing the intron box7 is sufficient for the regulation of oxi3 by cob (BOX phenotype); two sequences (containing intron loci box3 and box10) upstream in cob and two in oxi3 are dispensable. (ii) Strains without the two sequences upstream still contain the downstream sequence and the competence to specify a functional trans-acting element. Mutational lesions in this segment are phenotypically indistinguishable from box7 mutants, including the accumulation of polypeptides with homologous amino acid sequences. (iii) A catabolite-sensitive BOX phenotype, characteristic of mutants in the first exon, requires the simultaneous presence of an adjacent intervening sequence. A model is presented in which a hypothetical product specified by an intron (locus box7) of the cob gene controls the expression of a second mosaic gene (oxi3).

DNA Restriction Enzymes↗
PubMed1981

Evaluation of blood pressure in vasectomized and nonvasectomized men.

We assessed the effect of vasectomy on blood pressure by collecting cross-sectional data on the systolic and diastolic blood pressure of 946 male volunteer blood donors; of these, 30% were vasectomized. We used analysis of multiple covariance to correct both pressures for variation in age, weight, and height. Vasectomized and nonvasectomized men did not differ significantly in mean systolic or diastolic blood pressures. However, many of these men had been vasectomized for only a short period of time. We analysed the vasectomy subsample by multiple regression to determine whether blood pressures adjusted for age, body mass index, and height changed with time since vasectomy and found a slight, but non-significant, rise in the systolic pressure with square of time since vasectomy. The data are sufficiently strong to raise concern that data from a sample of men who have been vasectomized for longer periods of time would have shown a more dramatic increase.

Adult↗
PubMed1981

Evaluation of male infertility with an in vitro cervical mucus penetration test.

The use of an in vitro bovine cervical mucus penetration test (CMPT) provides unique data for fertility assessment. Flat capillary tubes were filled, kept frozen until use, exposed to a subsample of semen for 90 minutes, and microscopically evaluated. Adequate penetration was based on results of semen specimens from donors used for artificial insemination. of 161 patients being evaluated for infertility, 37% had semen that penetrated the CMPT inadequately. Of the patients with inadequate penetration, 70% had sperm densities of greater than 21 x 10(6)/ml, and 62% had over 50% motility. Thus neither evaluation of count nor motility provided the same information as the CMPT. Human spermatozoa had a similar swimming pattern in human and bovine mucus. Spermatozoa that exhibited poor in vitro penetration of human mucus also failed to penetrate bovine mucus. Comparison of the CMPT with postcoital tests of 42 couples revealed a good correlation. When the incidence of pregnancy for individuals with adequate and inadequate penetration was compared, more individuals with a good CMPT caused a pregnancy. It appears that the CMPT, an easy office test, allows greater discrimination of sperm function than semen analysis alone and is a useful tool for the diagnosis and management of infertility.

Animals↗
PubMed1981

Cervical mucus penetration test for in vitro assay of vaginal contraceptive agents.

An in vitro penetration test employing bovine cervical mucosa to evaluate vaginal contraceptives is presented. Its usefulness for the evaluation of the potency of a formulation in preventing sperm penetration was assessed by comparison of five commercially available preparations, with the use of both human and primate spermatozoa. The results were compared with those obtained with a spermicidal test (Sander-Cramer method) and in vivo with the use of the primate Macaca arctoides. Analysis of the two in vitro tests and the one in vivo test showed a significant degree of concurrence. The cervical mucus test much more closely reflected in vivo results than the Sander-Cramer test. A recommendation is made regarding the type and order of in vitro and in vivo methods to be used for the development and/or testing of new formulations.

Animals↗
PubMed1980

Mosaic organization of a mitochondrial gene: evidence from double mutants in the cytochrome b region of Saccharomyces cerevisiae.

The region coding for apocytochrome b in the mitochondrial genome of Saccharomyces cerevisiae is believed to exhibit a mosaic organization, consisting in certain strains of five exons and four introns. This model can be tested by the use of double mutants, each containing two physically, genetically and phenotypically defined mit- lesions in cis, (that is, in the same mitochondrial chromosome). Such mutants have been constructed, and the phenotypes of several examples of each of the four possible classes--exon-exon, exon-intron (downstream), intron (upstream)-exon and intron-intron--have been examined. Our results have shown that upstream mutations are always epistatic to downstream ones for polypeptide products, and that regulation of expression of cytochrome oxidase subunit I by introns is epistatic regardless of position. These findings have provided an independent verification of the mosaic model, and also suggest that at least the majority of novel polypeptides accumulating in intron mutants are hybrid products that contain sequences of the wild-type polypeptide.

Apoproteins↗