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Biomedical subjects

N J Alexander

Publications and source records attributed to N J Alexander.

At least 127 records · Page 7Linked to original sources
PubMed1980

Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.

We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations made in this study, we suggest that the antisperm antibodies that form after vasectomy may result in circulating immune complexes that exacerbate atherosclerosis.

Animals↗
PubMed1980

Monocytic orchitis and aspermatogenesis in normal and vasectomized rhesus macaques (Macaca mulatta).

The immunopathologic findings in the testes and kidneys of 25 long-term vasectomized monkeys and of 13 age-matched control animals were compared. Antisperm antibody was found in serum samples from 60% of vasectomized monkeys and in no samples from control animals. Orchitis, aspermatogenesis, or both, resembling allergic orchitis, was noted in 92% of vasectomized animals and in 23% of controls. Epididymitis and epididymal granuloma occurred exclusively in the vasectomized animals (52%). By immunofluorescence, granular deposits of IgA, IgG, and/or C3 in the basal lamina of the ductuli efferentes and the caput epididymidis were detected in 45% of the control monkeys. In vasectomized animals, the incidence of immune deposits increased to 91%, and the deposits became more widespread. Although both vasectomized and control animals had IgM, IgG, or both, in the glomerular mesangial region, C3 was found in vasectomized monkeys only (29%). The results of this study indicate that monocytic infiltrations with aspermatogenesis in association with immune deposits along the excurrent duct normally occur in subhuman primates, and that these changes increase in incidence after vasectomy. Although the testicular disease highly resembles allergic orchitis, an immunologic basis remains to be established.

Animals↗
PubMed1979

Regulatory interactions between mitochondrial genes. I. Genetic and biochemical characterization of some mutant types affecting apocytochrome b and cytochrome oxidase.

The region of the mtDNA containing the structural gene for apocytochrome b is called the cob or box region. There is evidence that the same region is also involved in the regulation of cytochrome oxidase. We have isolated eight mit- mutants in this region and have ordered them using petite deletion mapping. Four of these mutants appear to map outside the boxII region on the oli2-proximal end. Analysis of restriction endonuclease fragments of the mtDNA from peptides used in the deletion mapping suggests a minimum size of 3.1 x 10(3) base pairs for the whole cob region. Although none of our mutants contained any cytochrome b or cytochrome b-linked activities, polypeptides apparently related to apocytochrome b were present in some but not all mutants. Additional regulatory effects (both positive and negative) on cytochrome oxidase by virtue of control of its subunit I were also observed. In addition to these phenotypic traits, some of the mutants accumulated novel, mitochondrially translated polypeptides not seen in wild type.

Apoproteins↗
PubMed1979

Regulatory interaction between mitochondrial genes. II. Detailed characterization of novel mutants mapping within one cluster in the cob2 region.

These studies describe the properties of three mit- mutants designated EM17, EM25, and PZ1, all mapping at two closely linked sites near one of the boundaries of the region of the mitochondrial genome concerned with the specification of cytochrome b. They all exhibit complex phenotypes affecting cytochrome b, cytochrome aa3, and additional polypeptides not found in the wild type. In the case of EM 17 this complexity can be ascribed to the presence of two mutations induced in the course of the initial mutagenic treatment: one, the cob2 mutation proper, is responsible for the loss of cytochrome b which is replaced by an altered, functionally inactive polypeptide, cytochrome b. This polypeptide can be further modified, or even eliminated, by the controlled introduction of another mutation in the cob1 segment of the cob region. The reduction in cytochrome oxidase subunit I, responsible for the effects on cytochrome aa3 and enzymatic activity in EM17, is due to a second (not mit-) mutation that has been located in the par1-proximal segment of the oxi3 region. This second mutation as well as the cob mutation can be overcome, and the respective aspect of wild type function restored to EM17, by recombination with rho- strains retaining the appropriate segment(s) of the wild type genome. The phenotype of the other two mutants is due to a single mutagenic event. This conclusion is confirmed by their ability to restore wild type functions by reversion. The mutation in EM25 appears to be due to a frameshift, which has led to premature chain termination, producing a polypeptide of Mr = 15,000 related to apocytochrome b. This change is accompanied by a decrease in the amount of subunit I of cytochrome oxidase. Revertants fall into three classes: on galactose two produce a polypeptide indistinguishable from apocytochrome b, but vary in its amount, while the third fails to increase apocytochrome b above mutant levels. Production of subunit I is increased but fails to reach wild type levels. Complete restoration of wild type functions can, however, be obtained by recombination of EM25 with rho- (cob2+) strains. Mutation PZ1 results in a complete absence of any polypeptide related to apocytochrome b and of cytochrome oxidase subunit I. These cells produce a novel polypeptide with a Mr = 45,000 not found in the wild type, and unrelated to all its normal polypeptides. Reversion or recombination with rho- (cob2+) strains results in virtually complete restoration of all wild type functions and the elimination of the novel polypeptide.

Apoproteins↗
PubMed1979

Clomiphene citrate therapy for male infertility.

We have summarized 697 reported cases of the use of clomiphene citrate for the improvement of semen quality. Basal levels of gonadotropins are useful criteria for the differential diagnosis of hypo- and hypergonadotropic hypogonadism. Patients with an intact hypothalamic-pituitary-gonadal axis are most likely to respond to clomiphene citrate. Twenty-five mg. per day, administered in a cyclic fashion for a period of six to nine months, caused the greatest improvement. A higher dose (50 mg. per day) may be effective in men who do not respond to 25 mg. During the course of therapy gonadotropin levels and semen samples should be analyzed periodically. This drug is not currently approved for use in men; the incidence of side effects, particularly with long-term treatment, is unknown.

Clomiphene↗
PubMed1979

Vasovasostomy: evaluation of success.

Our review of 2,685 cases of vasovasostomy reported between 1948 and 1977 shows that many different surgical techniques can be successful. However, various reporting practices have made case comparisons difficult. We suggest a standardized method for reporting vasovasostomy results.

Female↗
PubMed1979

Induced varicoceles in rhesus monkeys.

Varicoceles were surgically induced unilaterally in seveh rhesus monkeys. Effects of the varicoceles were documented by quantitative and qualitative changes in the semen analysis and testicular biopsies. Testicular temperatures appeared to be higher bilaterally in animals with varicoceles. Testosterone and estradiol levels in the testicular vein were somewhat higher on the experimental side. We found no evidence for adrenal retrograde flow.

Animals↗
PubMed1978

Vasectomy increases the severity of diet-induced atherosclerosis in Macaca fascicularis.

Diet-induced atherosclerosis developed more extensively in vasectomized cynomolgus monkeys (Macaca fascicularis) than in sham-vasectomized control monkeys fed the same diet. The effect was most pronounced in the abdominal aortas, carotid arteries, distal segments of the coronary arteries, and intracranial cerebral arteries. Antibodies to sperm developed in all vasectomized monkeys, and complement and immunoglobulins were associated with atherosclerotic plaques in some of the vasectomized animals. The immunological response to sperm antigens that often accompanies vasectomy may exacerbate atherosclerosis.

Animals↗
PubMed1978

Immunofluorescence titres of sperm centrifuged at different speeds.

Two washing procedures were used on spermatozoa to test the effect of centrifugation on immunofluorescent staining. The rapidly centrifuged spermatozoa often exhibited a loss of acrosomal but an increase in tail antigenicity. A standard technique of sperm preparation for immunofluorescence is recommended in order to have reliable and comparable results.

Acrosome↗
PubMed1978

Coagulation changes following vasectomy: a study in primates.

Thirty vasectomized rhesus monkeys were tested for changes in coagulation factors that might reflect an increased incidence of thrombosis. The results of tests on these monkeys were compared with results of tests on 18 control rhesus monkeys; there were no significant differences between control and vasectomized animals for any of the parameters tested. One vasectomized animal had increased levels of fibrin monomer in his plasma on repeated samples, but no evidence of thrombosis on postmortem examination.

Animals↗
PubMed1977

Immunological and morphological effects of vasectomy in the rabbit.

Half of the rabbits developed antisperm antibodies (measured by either indirect immunofluorescence or sperm immobilization tests) after either a unilateral or bilateral vasectomy. The raised antibody levels, particularly six months or longer after vasectomy, often accompanied patchy orchitis. Seminiferous tubules from such animals exhibited sloughed, multinucleated, and immature germinal cells which were engulfed by phagocytic cells. Mononuclear infiltrates were occasionally present. The basal lamina infolded and thickened by means of supernumerary layers and appeared to be endocytosed by cells of the seminiferous tubules. Four months after vasectomy, numerous phagocytic cells were seen in migrate through the intact epithelium of zone 1 in the caput epididymidis, and were particularly prevalent in animals that exhibited testicular damage. These macrophages may serve to present sperm antigens to lymphocytes.

Animals↗