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S R Plymate

Publications and source records attributed to S R Plymate.

86 records · Page 5Linked to original sources

The association of D-group chromosomal translocations and defective spermatogenesis.

D-group chromosome translocations have been associated in isolated cases with infertility in males. In this study, we demonstrated the effect of a translocated D-group chromosome on spermatogenesis as it had segregated among three male members of one family. Although the father, who carried the translocation, was obviously fertile, the effects of the translocations on his sperm were noted in the morphologic examination. This study demonstrates the need for more careful evaluation of patients with chromosomal abnormalities for effects on spermatogenesis. Furthermore, it shows the possibility of autosomal chromosomal influences on testicular function.

Adult↗

Prevalence of circulating HL-A lymphocytotoxic antibodies in men after vasectomy.

Thirty-two men undergoing vasectomy were studied for one year to determine presence of HL-A antibodies after surgery. Blood samples were taken prior to vasectomy and at three, six, nine, and 12 months following surgery. Twenty-six men showed no increase in antibody activity during the study when their sera were matched against a 25-member typed lymphocyte donor panel. Sera of two men showed a definite increase in positive reactions, six to 12 months after surgery. The sera of four men showed slight increases in reactivity between three and 12 months after vasectomy. The serum of one man showed a single positive reaction against his own lymphocytes three months after surgery, but no positive reactivity against the lymphocyte donor panel. These studies suggest that HL-A antibodies are not regularly formed as a result of standard vasectomy procedures, but that further long-term evaluation of vasectomized patients may be needed to make definite conclusions.

HLA Antigens↗

Activation of palmitic acid by human spermatozoa.

Human spermatozoa were studied to determine if a long chain fatty acid, CoASH ligase (AMP) (E.C. 6.2.1.3), was present. Ligase activity was measured with a radioligand millipore filter technique and was readily detectable in spermatozoa or in the protein fraction extracted with Triton X-100, but was not present in seminal plasma. The assay was optimized for pH, protein concentration, and incubation time. Activity was dependent upon palmitic acid, ATP, coenzyme A, and a divalent cation. Sperm ligase appeared similar to the ligase characterized from other tissues by sharing a common pH optimum (approximately 8.0-8.4), and a preference for magnesium over manganese in the incubation media.

Adenosine Triphosphate↗

Kinetics of human spermatozoa long-chain fatty acid: CoASH ligase.

The kinetics of long-chain saturated fatty acid activation were studied in the supernatant obtained from Triton-treated human spermatozoa. Sperm long-chain fatty acid: CoASH ligase (AMP) (E.C. 6.2.1.3) was able to activate myristic, palmitic, and stearic acids, but was incapable of utilizing lauric, arachidic, and behenic acids. Peak activity was obtained with palmitic acid. Although the Kms for each fatty acid were similar (4.3 to 5.0 microM), the Vmax was several-fold higher for palmitate. In contrast, ligase from liver homogenates assayed under identical conditions activated lauric through stearic acids, with maximal rates being noted with myristic acid. When compared with nongerminal tissues, sperm ligase appears unique because of its narrower acyl substrate specificity.

Adenosine Triphosphate↗

Phosphatidylcholine synthesis in human spermatozoa.

To clarify the mechanism of phospholipid synthesis in spermatozoa, fresh human spermatozoa were incubated with labeled fatty acids and 1-acyl-lysophosphatidyl choline (LPC) in the presence or absence of coenzyme A (CoASH). Both docosahexaenoic acid and palmitic acid were incorporated into phosphatidylcholine; however, this reaction was absolutely dependent upon the presence of CoASH in the incubation medium. The rate of incorporation of docosahexaenoic acid was 2.7-fold higher than that of palmitic acid, but more palmitic acid was incorporated into phosphatidylcholine in the absence of LPC. These data provide direct evidence for acyl transferase activity in human spermatozoa and may furnish a mechanism for phospholipid remodeling in sperm membranes. The different incorporation rates of these fatty acids into phosphatidylcholine may be due to the kinetics of the activation step, long chain fatty acid:CoASH ligase (AMP), or the substrate specificity of the acyl transferase.

Coenzyme A↗

Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men.

The circadian pattern in levels of serum total testosterone (T) in men becomes blunted with normal aging. However, because T not bound to sex hormone-binding globulin (non-SHBG-T) is felt to be a better representative of biologically available T than is total T, the possibility of a 24-h variation in non-SHBG-T in young men and the possibility that aging is associated with a blunting of that rhythm were investigated. Hourly blood samples were drawn on 10 normal young men (mean age 27.3 years) and 10 normal elderly men (mean age 70.7 years) over a 24-h period and the serum was assayed for total T, sex hormone-binding globulin (SHBG), and total protein; non-SHBG-T was calculated. SHBG was determined by radioimmunoassay as well as by a steroid-binding assay. Young men had a significantly higher (p less than 0.05) mean 24-h level of non-SHBG-T (1.91 +/- 0.62 nm/l) than did the elderly men (0.86 +/- 0.01 nM/l). Also, each young man showed a significant circadian rhythm in non-SHBG-T, with a group mean daily variation of 1.42 +/- 0.38 nM/l. In contrast, only 60% of the elderly men demonstrated a significant circadian rhythm in non-SHBG-T, and the group mean rhythm was blunted (maximum excursion 0.38 +/- 0.07 nM/l) compared with that of the young men. SHBG and total protein levels demonstrated similar 24-h variations in the two age groups. It was concluded that non-SHBG-T serum levels, similar to serum total T levels, demonstrate a circadian pattern in young men and this circadian rhythmicity becomes blunted with normal aging.

Adult↗

Activation of pro-apoptotic p38-MAPK pathway in the prostate cancer cell line M12 expressing a truncated IGF-IR.

The type I insulin-like growth factor receptor (IGF-IR) plays a critical role in signaling survival and proliferation in many cell types. Activation of IGF-IR by its ligands promotes cell proliferation via mitogen-activated protein kinase (MAPK) cascade and cell survival via phosphoinositide 3-kinase (PI3K) cascade. The IGF-IR emerges as a powerful growth factor for many tumor cells. A truncated IGF-IR 486/STOP, described as a dominant negative IGF-IR mutant, was shown to induce apoptosis and inhibit tumor growth in vivo while endogenous IGF-IR was activated. To investigate the mechanism(s) of the action of 486/STOP, we have introduced 486/STOP into the prostate tumor model cell line M12 and its derivative M12lisn that expresses high levels of wild type IGF-IR. We have found that 486/STOP induces apoptosis in M12 and M12lisn cells in culture and that 486/STOP acts through activation of the pro-apoptotic p38-MAPK without interfering with wild type IGF-IR activation. In addition, our results have indicated that 486/STOP induced activation of p38-MAPK increases through activation of endogenous IGF-IR. These data suggest that activation of the IGF-IR by 486/STOP can selectively enhance the previously reported IGF-IR pro-apoptotic signaling pathways.

Apoptosis↗

Seminal fluid androgen binding protein.

The following study was undertaken to determine the presence of an androgen binding protein (ABP) in the ejaculate. Seminal fluid was obtained from ten fertile subjects. Sperm counts ranged from 20 x 106/cc to 80 x 106/cc. Each sample was preincubated with tritiated dihydrotestosterone (DHT) and examined by polyacrylamide gel electrophoresis (PAGE). Second, after preincubation of the samples with tritiated DHT, the samples were mixed with Concanavalin-A bound to sepharose-D (C-S) and the supernate separated and counted. Finally, saturation analysis of the samples using dextran-coated charcoal for separation and counted. Finally, saturation analysis of the samples using dextran-coated charcoal for separation was performed and Scatchard analysis was used to determine the concentration of ABP present. PAGE demonstrated ABP in seven of ten samples studied. The bound counts of DHT were removed by C-S. The concentrations of ABP ranged from 0.132 to 0.468 nanomoles ABP/dl semen. These data indicate there is an ABP in seminal fluid similar to that from the Sertoli cell.

Androgen-Binding Protein↗

Familial thioamide-induced lupus syndrome in thyrotoxicosis.

We describe 2 relatives both with thyrotoxicosis who developed a lupus-like syndrome after treatment with thioamide derivatives, methimazole (father) and propylthiouracil (son). The lupus syndrome consisted of joint pains, skin rash, and positive antinuclear antibodies (son), all of which resolved after discontinuation of the antithyroid medications. Both patients were identical at the HLA-DR locus suggesting adverse reactions to thioamides may be controlled by immune response genes. The clinician should be cautious about treating other family members when 1 member has had a drug-induced lupus syndrome. This is especially true if the disease in question is a known familial illness such as thyrotoxicosis.

Adolescent↗

Synthesis of docosahexaenoyl coenzyme A in human spermatozoa.

The synthesis of docosahexaenoyl coenzyme A (22:6-CoA) was studied in a long-chain fatty acid: CoASH ligase (AMP)-enriched fraction from human spermatozoa and was compared to palmitoyl CoA (16:0-CoA) synthesis. The pH optimum for 22:6 activation was 8.4, which was identical to the value obtained with 16:0. The Km for ATP was 0.5 mM when 22:6 was the acyl substrate; however, when 16:0 was incubated with the ligase preparation, the Km for ATP was 2.9 mM. When CoASH was varied and 22:6 was the fatty acyl acceptor, a pattern of negative cooperatively was observed. This was confirmed by a downwardly concave double-reciprocal plot, a Hill coefficient of 0.63, and an Rs in excess of 150. The Hill coefficient with 16:0 and CoASH was 0.94. Palmitic acid was demonstrated to be a competitive inhibitor of 22:6-CoA synthesis. Based upon these data, we conclude that the kinetics of spermatozoan ligase are complex, and, in addition, these data support the hypothesis that 22:6 may regulate ligase activity, and therefore free fatty acid utilization, in sperm.

Acyl Coenzyme A↗