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Biomedical subjects

K D Smith

Publications and source records attributed to K D Smith.

At least 163 records · Page 9Linked to original sources
PubMed1979

Leydig cell density and function and their relation to gonadotropins in infertile oligospermic men with varicocele.

Circulating gonadotropin and testosterone levels in infertile men with varicocele and sperm counts of less than 10(7)/ml were correlated with testicular Leydig cell density and in vitro testosterone synthesis. A significant correlation was found between Leydig cell density and both plasma testosterone levels and in vitro testosterone synthesis. Luteinizing hormone (LH) levels paralleled the in vitro testosterone synthesis. Although in the majority of patients, in vitro testosterone synthesis and Leydig cell density were low, plasma testosterone and LH levels were within the normal range. The only abnormal circulating hormonal level was high follicle-stimulating hormone in the most severely oligospermic patients. No difference were found between the right and left testes with regard to in vitro testosterone synthesis or Leydig cell density, and no correlation with patient age or site or degree of varicocele could be demonstrated. These findings suggest that Leydig cell dysfunction was the mechanism responsible for the oligospermia and infertility of these patients.

Adult↗
PubMed1979

A molecular basis for hemoglobin-H disease in American blacks.

We have applied gene counting and restriction endonuclease mapping techniques to the study of two American black families in which there were one or more cases of HbH disease. We found deletions of three of the four normal alpha-globin genes in individuals with HbH disease. In two of these individuals, the chromosome containing the single alpha gene could have originated by crossing over between mispaired alpha genes, resulting in a deletion of about 4.2 kilobases (kb).

Black People↗
PubMed1978

Quantitation of Leydig cells in testicular biopsies of oligospermic men with varicocele.

Leydig cell density was evaluated quantitatively in bilateral testicular biopsies from 16 oligospermic men with varicocele. The method utilized for this quantitation is based on the determination of the total number of Leydig cells, Leydig cell clusters, and seminiferous tubules in the entire histologic section of each biopsy, and the calculation of the following indices: mean Leydig cells per seminiferous tubule, mean Leydig cell clusters per seminiferous tubule, and mean Leydig cells per cluster. A significant correlation between Leydig cells per tubule and Leydig cell clusters per tubule was demonstrated, suggesting that determination of Leydig cell clusters per seminiferous tubule in testicular biopsies is an objective and clinically applicable method for quantitative evaluation of Leydig cell density. An association of varicocele with Leydig cell hyperplasia was not noted for the 16 patients studied. In addition, no significant differences in Leydig cell density between right and left testes were found, and no correlation between Leydig cell density and site or degree of varicocele, or age of the patients could be demonstrated. To our knowledge this is the first report of quantitative analysis of Leydig cell density in men with varicocele.

Biopsy↗
PubMed1978

Quantitative analysis of the seminiferous epithelium in human testicular biopsies, and the relation of spermatogenesis to sperm density.

Quantitative analysis of the seminiferous epithelium was performed in bilateral testicular biopsy specimens from 14 patients with sperm counts ranging from 0 to 89 million/ml. All Sertoli cells and germ cells within each seminiferous tubule cross-section were counted in all biopsies. Results were expressed either as number of cells per unit length of seminiferous tubule circumference or as number of cells per Sertoli cell. Results were correlated with sperm count (millions per milliliter), total sperm count (millions per ejaculate), and age. A significant correlation between sperm density and germ cell counts was demonstrated. Coefficients of correlation were higher when results were expressed per unit of tubular wall length than when expressed per Sertoli cell. In men with sperm counts below 5 million/ml the number of germ cells in the biopsy was lower than in men with higher sperm counts. Spermiogenesis appeared to be most affected. In this group of patients an adverse effect of age on spermatogenesis was noted.

Adolescent↗
PubMed1978

A possible mechanism for the detrimental effect of varicocele on testicular function in man.

Seminiferous epithelium histology, Leydig cell density, and in vitro testosterone synthesis were quantitated in bilateral testicular biopsies from men with varying degrees of unilateral or bilateral varicoceles. Results were correlated with plasma levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone (T), as well as with semen quality. In patients with bilateral varicoceles, spermatogenesis, Leydig cell density, plasma T levels, and in vitro T synthesis were significantly lower than in patients with unilateral varicoceles. Varicoceles appeared to affect maximally the latest stages of spermatogenesis. A negative correlation between FSH and LH levels and spermatogenesis was observed; however, a dissociation between the two gonadotropins occurred when spermatogenesis declined. Plasma T levels were within the normal range in all patients. The T:LH ratio was significantly correlated with spermatogenesis and sperm motility. Leydig cell density was abnormally low in oligospermic patients, and it was significantly correlated with in vitro T synthesis, spermatogenesis, sperm motility, and semen volume. Sperm count and motility were significantly correlated in this group of patients, suggesting a common pathophysiology for the effect of varicocele on spermatogenesis and sperm motility. This common pathophysiology appears to be disturbed Leydig cell function resulting in decreased testicular androgen production, in turn causing inadequate spermatogenesis and epididymal function.

Adolescent↗
PubMed1978

Relationship of varicocele to sperm output and fertility of male partners in infertile couples.

Both partners of 455 infertile couples seen consecutively were evaluated. When indicated the female partners were treated. Six semen specimens from each male subject were analyzed. A varicocele was diagnosed in 23.7 per cent of the men. More than 60 per cent of the men with a varicocele had sperm counts less than 40 million per ml., while 67 per cent without a varicocele had sperm counts more than 40 million per ml. The mean and total sperm counts of men with a varicocele were significantly lower than those without a varicocele. However, the pregnancy rates were not significantly different. The pregnancy rate was 46 per cent in couples whose male partners underwent a varicocelectomy, not significantly different from the pregnancy rate achieved in couples when the varicoceles were not corrected surgically (51 per cent). Varicocelectomy resulted in improvement in sperm count only when preoperative counts were more than 10 million per ml. Pregnancy rates for couples in which a varicocelectomy did or did not result in improvement in sperm count or motility were identical (45.1 and 45.5 per cent, respectively). These findings suggest that in male partners of infertile couples the presence of a varicocele is associated with compromised semen quality but not with diminished fertility when the female partners are treated. This observation emphasizes the importance of considering infertility as a problem of a couple, rather than a specific disorder of one of the partners.

Cell Count↗
PubMed1978

The proportion of all point mutations which are unacceptable: an estimate based on hemoglobin amino acid and nucleotide sequences.

Statistical analysis of the distribution of 156 kinds of human hemoglobin beta (Hbbeta) chain variants suggests that mutations are essentially random in their location. Thus differential fitness, not differential mutability, is the principal source of nonrandom distribution of interspecies differences in Hbbeta amino acid sequence. Similar analyses of both the location and the kind of interspecies differences detected among primates support this viewpoint and lead us to estimate that at least 95% of all amino acid subsitutions,i.e., nonsynonymous mutations, in Hbbeta are functionally unacceptable in homozygous state. Through the combined use of this estimate and the number of nonsynonymous and synonymous substitutions per nucleotide site inferred from comparisons of entire human and rabbit HbbetamRNA nucleotide sequences, we calculate (a) approximately 70% of synonymous Hbbeta mutations are adaptively undersirable and (b) the mutation rate underlying all changes is lesser than or equal to 10(-8) nucleotide substitutions per nucleotide site per year. Apart from such calculations, analyses of nucleotide patterns in HbbetamRNA as well as in rat preproinsulin mRNA reinforce the notion that a large portion of synonymous mutations are functionally unacceptable and rendered so by selective constraint, at a pretranslational level, of the abundance of particular nucleotide doublets such as CpG.

Amino Acid Sequence↗
PubMed1978

Suggestion of abnormal testicular steroidogenesis in some oligospermic men.

Androgen biosynthesis in the testis may be analyzed in some detail by means of techniques of in vitro incubation of small testicular biopsy specimens with suitable radiolabelled precursors. Sixty-six tissue specimens from 33 patients who underwent bilateral testicular biopsies because of infertility were incubated in vitro with [3H]pregnenolone in order to investigate the possibility of abnormalities in their steroid biosynthetic activity. As a normal control, testicular tissue obtained by testicular biopsy from a young normal volunteer was used. The distribution of metabolites in the incubates of testes from 8 infertile men differed greatly from the remaining 25 patients and the normal control. The major steroids formed from pregnenolone by the testes of those 8 men were 17-hydroxypregnenolone, dehydroepiandrosterone, 20alpha-dihydropregnenolone and and 20alpha-dihydro-17-hydroxypregnenolone. Very small amounts of delta4-3 oxo products (progesterone, 17-hydroxyprogesterone, androstenedione and testosterone) were formed suggesting a deficiency of 3beta-hydroxy-steroid-dehydrogenase activity in the testes of these 8 men, possibly related to the derangement of their spermatogenic function.

Adult↗
PubMed1977

In vitro steroid metabolic studies in human testes I: Effects of estrogen on progesterone metabolism.

A technique of incubation of testicular tissue in vitro with radiolabeled precursors was applied in the investigation of the steroid biosynthesis by testes of four young men after long-term, high-dose estrogen treatment. A positive correlation between plasma and testicular steroid levels, and in vitro capacity of the testes to metabolize progesterone was demonstrated. Estrogen administration produced a very significant inhibition of plasma and testicular levels of testosterone. The in vitro synthesis of testosterone from progesterone was very severely impaired; especially 17alpha-hydroxylation of progesterone. 20alpha-hydroxysteroid-dehydrogenase activity was found to be increased after estrogen treatment, both in vivo and in vitro. These findings suggest that testicular 17alpha-hydroxylase activity (and possibly also 17-20 lyase activity) is either under gonadotropin regulation, or is directly suppressed by estrogen. This could result by decreased enzyme synthesis, direct enzyme inhibition or affectation of the cofactors or cytochromes necessary for the enzymatic activity. 20alpha-reduction of C21-steroids would represent an alternative pathway for their catabolism, not regulated by gonadotropin or not affected by estrogen, that would be significant in situations with reduced 17alpha-hydroxylase activity.

Adult↗
PubMed1977

Frequency distribution of sperm counts in fertile and infertile males.

In this study the frequency distribution of sperm counts and total sperm counts from more than 4000 allegedly fertile males were compared with those of husbands in 1000 infertile couples. Significant differences were observed only at the lower end of the scale (sperm counts below 10 million/ml and total sperm counts below 25 million/ejaculate). Frequency distributions of sperm counts above 10 million/ml or total sperm counts above 25 million/ejaculate revealed little difference between the fertile and infertile groups. These data suggest that, unless other parameters are found to be abnormal, sperm counts and total sperm counts above 10 million/ml and 25 million/ejaculate, respectively, probably are not major factors in a couple's infertility.

Cell Count↗
PubMed1977

Relation between indices of semen analysis and pregnancy rate in infertile couples.

Both partners of 198 consecutive infertile couples were evaluated. Studies in the female included clinical evaluation of ovulation for a minimum of two menstrual cycles, investigation of tubal patency, and evaluation of sperm survival in cervical mucus. Six semen specimens were analyzed from each male. Laparoscopy, scrotal exploration, and testicular biopsies were performed as required. Where indicated, the female was treated intensively. The only therapy offered to the males was ligation of varicoceles, if present. The couples were grouped on the basis of sperm counts, total sperm counts, motile sperm counts, and total motile sperm counts, and the incidence of pregnancy was computed. Pregnancy rates of approximately 50% occurred in couples where sperm counts or total sperm counts were in the range of 5 to 60 million/ml or 25 to 200 million/ejaculate, respectively. When sperm counts were over 60 million/ml or total sperm counts over 200 million/ejaculate, pregnancy rates increased to above 70%. These observations emphasize the importance of considering infertility as a problem of a couple rather than as a specific disorder of one of the partners. These data also demonstrate a lack of direct correlation between sperm density in the ranges of 5 to 60 million/ml and pregnancy rates in couples where the wife is treated intensively.

Cell Count↗
PubMed1977

In vitro steroid metabolic studies in human testes. II: Metabolism of cholesterol, pregnenolone, progesterone, androstenedione and testosterone by testes of an estrogen-treated man.

The effect of long-term in vivo estrogen treatment on in vitro steroidogenesis by the testes of a young man was investigated. In vitro incubation of testicular tissue of this man with 3H-pregnenolone, 3H-progesterone, 3H-androstenedione and 3H-testosterone demonstrated suppression of 17-hydroxylase activity, with little or no effect of the treatment on delta5-3beta-hydroxysteroid oxidoreductase, 5alpha-reductase and aromatase. Increased 20alpha-hydroxysteroid oxidoreductase activity was observed. Determination of intratesticular steroid concentrations led to similar conclusions.

Adult↗
PubMed1977

Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants.

A number of individuals with aberrant Y chromosomes have been tested for the presence of Y-chromosome-specific reiterated DNA. These studies locate Y-chromosome-specific reiterated sequences on the long arm of the Y chromosome. Correlation with phenotype and other known Y chromosome markers establish that the Y-chromosome-specific reiterated DNA discussed here has no evident role in male determination.

Base Sequence↗