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Biomedical subjects

K D Smith

Publications and source records attributed to K D Smith.

At least 145 records · Page 8Linked to original sources

Circannual rhythm in human sperm count revealed by serially independent sampling.

Sperm concentration and total sperm counts from single semen and samples from each of 4435 patients requesting vasectomy between September 1972 and December 1977 were analyzed for circannual (about 1 year) rhythmicity. Although large temporal variations were found both between years and within years, a trend was noted for higher sperm concentration during the winter than during the summer. When the entire series of data were analyzed by months, a strong circannual pattern was apparent, with the highest sperm counts between February and March and the lowest counts during September. To the authors' knowledge, this is the first report of a circannual rhythm in human sperm concentration and total sperm count. The data must be considered preliminary, but if confirmed by other investigators studying comparable populations, the influence on clinical investigations will be profound.

Adult↗

Endocrine problems and treatment.

All drugs employed for the purpose of improving sperm production, motility, viability, and morphology may be expected to have positive effects in some patients. However, the wide variation in these measures in all men make the confirmation of beneficial effects difficult. It is likely that definitive therapy of the infertile male will not be very successful until the causes of idiopathic oligospermia can be clearly elucidated. At that time, it is possible that definitive therapy may be devised. Until then, the clinician can expect to continue to read controversial reports about the effects of various therapeutic agents on male infertility. Even varicocele ligation, long considered one of the few definitive therapies of oligospermia or azoospermia does not appear to be equally effective in all series. In our own series, varicocele ligation has been of little benefit to those men who need it most, those with sperm counts below 10 million/ml (11).

Endocrine System Diseases↗

Isolation and characterization of cloned human DNA fragments carrying reiterated sequences common to both autosomes and the X chromosome.

Several recombinants were identified and purified from a cloned library of human DNA by virtue of their homology to DNA from a mouse-human hybrid cell line containing a single human chromosome, the X, and their lack of homology to mouse DNA. Three recombinants were characterized in detail, and all were homologous to reiterated DNA from the human X chromosome. These recombinants also were homologous to reiterated sequences on one or more human autosomes and, therefore, were not X chromosome specific. The recombinant DNA fragments homologous to human reiterated X DNA were the same fragments homologous to human reiterated autosomal DNA. Digestion of genomic DNAs with several restriction enzymes revealed that the pattern of fragments homologous to one recombinant, lambda Hb2, was the same on autosomes as on the X chromosome, suggesting that the molecular organization of these elements on the X is not distinct from their organization on autosomes.

Animals↗

Varicocele and the morphology of spermatozoa.

It is believed that varicocele is characteristically associated with specific abnormalities of spermatozoal morphology (increased numbers of tapered and amorphous forms). This report summarizes the results of a prospective study of spermatozoal morphology in 208 male partners of infertile couples seen consecutively during an 18-month period. After exclusion of 23 azoospermic males, sperm morphology in the remaining 56 patients with varicocele and 129 men without varicocele were compared. Although the incidence of abnormal spermatozoa was higher in patients with varicocele, no significant differences in the patterns of morphology were observed. In both groups of patients the percentage of normal spermatozoa was significantly correlated with the sperm count and with percentage motility. Sperm count and motility were significantly correlated with each other. The percentages of tapered and amorphous spermatozoa were inversely correlated with the motile sperm count. These results demonstrate that the pattern of spermatozoal morphology observed in men with varicocele is not characteristic or unique to this condition. It appears that abnormality of spermatozoal morphology is commonly associated with diminished sperm count and motility, regardless of the presence or absence of a varicocele.

Humans↗

The influence of ovulatory dysfunction and timing of insemination on the success of artificial insemination donor (AID) with fresh or cryopreserved semen.

The influence of ovulatory dysfunction and timing of insemination on the success of AID with either fresh or cryopreserved semen was investigated. A total of 238 patients were inseminated, resulting in 170 pregnancies during 1201 insemination cycles, an average of 5.0 cycles per pregnancy. Pregnancy rates were similar in those patients receiving either fresh or cryopreserved semen, but the number of cycles required for pregnancy to occur was doubled in the latter group. Ovulatory dysfunction further delayed the number of cycles before conception. The poorest results occurred in those patients with ovulatory dysfunction receiving cryopreserved semen. The timing of insemination was more important in patients receiving cryopreserved semen than those receiving fresh semen. With cryopreserved semen, pregnancy was not likely to occur unless the insemination was performed on the day of ovulation. These data suggest that frozen semen is less efficacious than fresh semen, a difference that is compounded by the presence of ovulatory dysfunction in the recipient. It is possible that an increase in the frequency of insemination from every other day to daily may improve the results of AID with cryopreserved semen.

Evaluation Studies as Topic↗

The menstrual cycle and plasma testosterone levels in women with acne.

A prospective study of the ovarian function and plasma testosterone levels was conducted in a group of 139 women presenting with a chief complaint of acne. In 90% of the patients the plasma testosterone levels were above the normal mean. Amenorrhea was present in 17.2%, anovulation in 18.4%, and variable degree of ovulatory dysfunction in 57.2% of the patients. The severity of ovarian dysfunction was directly proportional to the plasma testosterone levels. Age was inversely related to both plasma testosterone levels and severity of ovarian dysfunction. The results of this study suggest that acne may be associated not only with a hyperandrogenic state but also with ovarian dysfunction. They emphasize the need for a careful investigation of androgen levels and ovarian function in women with chief complaint of acne.

Acne Vulgaris↗

Population heterogeneity of the Hpa I restriction site associated with the beta globin gene: implications for prenatal diagnosis.

The Hpa I restriction endonuclease site polymorphism that results in some human beta globin genes being contained in a 13-kilobase (kb) DNA restriction fragment rather than in the usual 7.6-kb fragment has been reported to be in linkage disequilibrium with the beta S mutation. The frequency of the 13-kb fragment among Baltimore black sickle cell (SS) disease patients (58%) is lower than that reported for San Francisco black SS disease patients (87%) and similar to that reported for such New York patients (59%). There is, then, considerable heterogeneity among American black populations. Therefore, for the purposes of prenatal diagnosis, the frequency in the particular population at risk should be established. When the frequency of association of the 13-kb fragment and the beta S mutation is low, the linkage phase must also be established. When the linkage phase is known, the Hpa I pattern alone can exclude SS disease 54% of the time for Baltimore AS X AS couples.

Anemia, Sickle Cell↗

The molecular basis of hemoglobin Grady.

DNA from individuals heterozygous for the extended alpha-chain variant Hb Grady were studied by gene counting and restriction enzyme analysis. Neither method indicated the presence of an extra (fifth) alpha gene, which argues that if this variant arose by unequal crossing over, the event most likely involved mispairing between alleles rather than between the separate alpha 1 and alpha 2 loci.

Chromosome Mapping↗

Is semen cryopreservation helpful in testicular cancer?

Currently, semen to be "banked" by cryopreservation must have a minimum sperm concentration of 40 million/ml. and a minimum motility of 60 per cent. In analyzing semen of our patients with testicular cancer after unilateral orchiectomy but before further therapy, we have found that the semen of only 4 per cent (1/25) meets those minimum requirements. The results of this study suggest that cryopreservation may be an unrealistic solution to the infertility that may result from the treatment of testicular cancer.

Adult↗

Prenatal diagnosis of sickle cell anemia by restriction and endonuclease analysis: HindIII polymorphisms in gamma-globin genes extend test applicability.

Polymorphism for a Hpa I restriction endonuclease site associated with about 60% of beta S genes in American Blacks allows exact prenatal diagnosis of sickle cell anemia by amniocentesis in 36% of couples at risk. In three families in whom exact diagnosis by Hpa I sites was impossible, we found analysis for the presence of polymorphic HindIII sites in the G gamma and A gamma intervening sequences would allow an exact prenatal diagnosis of sickle cell status in all three. In one of these families, the presence of an A gamma HindIII site in amniocyte DNA confirmed the diagnosis (sickle cell trait) made by synthetic studies using fetal erythrocytes obtained at fetoscopy. Studies of other Black families and individuals provide evidence for linkage disequilibrium in the G gamma-A gamma-delta-beta gene complex involving the four sites, G gamma HindIII, A gamma HindIII, beta S, and Hpa I, which span 33 kilobases (kb). Ten of 14 chromosomes bearing a beta S gene in a 7.6-kb Hpa I fragment contained a G gamma but not an A gamma HindIII site, whereas 16 of 16 chromosomes bearing a beta S gene in a 13-kb Hpa I fragment lacked both the G gamma and A gamma HindIII sites. Two-thirds of beta A-bearing chromosomes lacked both G gamma and A gamma sites, whereas one-third contained either the G gamma or both G gamma and A gamma sites. These data demonstrate that combined analysis of both Hpa I and HindIII polymorphisms and verification of their linkage phase should increase the fraction of couples for whom amniocentesis can provide an exact diagnosis of sickle cell status from 36% to greater than 80%.

Anemia, Sickle Cell↗

Unequal crossing-over: a common basis of single alpha-globin genes in Asians and American blacks with hemoglobin-H disease.

The alpha-globin genes of five black Americans, two Chinese, and five Filipinos with HbH disease (an alpha-thalassemia state in which there is a single functional alpha gene) were analyzed by restriction endonuclease techniques. All subjects were found to have one chromosome 16, lacking both alpha genes, and another containing a single alpha gene (--/-alpha). Restriction endonuclease patterns of the DNA obtained from all 12 subjects were identical and compatible with unequal crossing-over as the mechanism of origin of the single alpha gene in these individuals.

Black People↗

Organization and heterogeneity of sequences within a repeating unit of human Y chromosome deoxyribonucleic acid.

Fragments of 3.4 kilobases (kb) are released from DNA of human males, but not DNA of human females, by cleavage with restriction endonucleases HaeIII, EcoRI, or EcoRII. Most, if not all, reiterated DNA which is specific for the Y chromosome (it-Y DNA) is present within these male-specific 3.4-kb molecules. Although such 3.4-kb molecules are themselves localized to the Y chromosome, this is not true for all sequences within them. At least two distinguishable types of reiterated sequences are found within each 3.4-kb molecule. One type consists of at least two families which are highly reiterated and are not confined to the Y chromosome. The other type is composed of an estimated minimum of 39 families, each moderately reiterated and localized to the Y chromosome. Y-specific and non-Y-specific sequences are interspersed with one another in the same 3.4-kb molecule. In the average 3.4-kb molecule, three 800 nucleotide lengths of Y-specific sequences alternate with four 250 nucleotide lengths of non-Y-specific sequences. Since the total number of families of Y-specific sequences, calculated on the basis of reiteration frequency and total abundance in a male genome, greatly exceeds the number of Y -specific sequences present in a single 3.4-kb molecule, it necessarily follows that the population of these 3.4-kb molecules is heterogeneous.

Base Sequence↗

Testosterone levels in female partners of infertile couples. Relationship between androgen levels in the woman, the male factor, and the incidence of pregnancy.

Plasma testosterone levels were measured in the female partners of 146 consecutive infertile couples. The incidence of hyperandrogenism in the woman was correlated with ovarian function, incidence of pregnancy, male factor, and response of plasma testosterone levels to prednisone treatment. Over 70 per cent of the patients had pretreatment testosterone levels above 40 ng. per 100 ml. while after a minimum of two months of therapy approximately 80 per cent had levels below 40 ng. per 100 ml. High levels of plasma testosterone were associated with significant prolongation of the follicular phase of the cycle and increased incidence of amenorrhea or anovulation. An over-all pregnancy rate of 50.4 per cent resulted from the treatment. A direct relationship between pregnancy rates and sperm density as well as between pregnancy rates and degree of suppression of plasma testosterone after therapy was observed. These results demonstrate a high incidence of hyperandrogenism in female partners of infertile couples. The effectiveness of glucocorticoid treatment appears to be related to suppression of excessive androgen levels. The data also suggest that infertility is a relative state related to the fertility potential of each member of the couple. Improvement of the fertility potential of either member may result in conception.

Amenorrhea↗

SV40 recombinants carrying rabbit beta-globin gene coding sequences.

We have constructed and propagated two SV40 recombinants in which different portions of the viral late gene region are replaced by a rabbit beta-globin coding sequence derived from a cloned cDNA (Maniatis et al., 1976). One of these recombinants, which retains the promoter, leader and intervening sequences for a viral late mRNA, directs the synthesis of a stable SV40-globin hybrid transcript. Using a sensitive radioimmunoassay, we have shown that this globin RNA is translated in infected monkey cells. A second recombinant, which retains the late region promoter but lacks the RNA splicing region, produces neither a stable globin transcript nor any detectable beta-globin. These experiments indicate that some sequence within a 500 bp SV40 segment, presumably the splicing region, is required for the accumulation of stable mRNA. They also demonstrate how hybrid transducing viruses can be used both to characterize viral regulatory sequences and to produce new gene products in cultured cells.

Animals↗

The relation between plasma testosterone levels and the lengths of phases of the menstrual cycle.

Plasma testosterone levels were measured in 331 women of reproductive age. The incidence of clinical signs of hyperandrogenism (hirsutism, acne) was recorded. Ovulatory activity was evaluated clinically by basal body temperature and frequent observation of changes in the appearance of the cervical os and cervical mucus. Plasma testosterone levels were abnormally elevated in patients with clinical signs of hyperandrogenism. The highest mean testosterone levels were noted in the group of hyperandrogenic women with amenorrhea. Significant prolongation of the follicular phase and shortening of the luteal phase were demonstrated to be associated with clinical signs of hyperandrogenism and elevated plasma testosterone levels. Statistically significant correlations between plasma testosterone levels and duration of phases of the menstrual cycle were observed. Testosterone levels were directly related to the length of the follicular phase and inversely related to the length of the luteal phase. A significant inverse correlation between the lengths of the two phases of the menstrual cycle was also demonstrated. These results suggest an association between hyperandrogenism and prolongation of the follicular phase and shortening of the luteal phase of the menstrual cycle, possibly related to the high incidence of infertility and menstrual irregularity reported for hyperandrogenic women.

Adult↗

Effect of prednisone on plasma testosterone levels and on duration of phases of the menstrual cycle in hyperandrogenic women.

A group of 106 women of reproductive age with laboratory and clinical evidence of hyperandrogenism was treated with prednisone. The daily dosage varied between 7.5 and 10 mg. Ovulatory activity was assessed prior to and during therapy by basal body temperature and observation of changes in the cervical os and cervical mucus. Plasma testosterone levels were significantly suppressed by prednisone therapy. This was associated with initiation of ovulatory activity in 5 of 14 (35.7%) amenorrheic patients and 10 of 11 (90.9%) anovulatory patients. In 81 ovulatory patients, prednisone therapy resulted in statistically significant shortening of the follicular phase and lengthening of the luteal phase of the menstrual cycle. The mean length of the menstrual cycle was unchanged. Significant correlations between percentage suppression of plasma testosterone and shortening of the follicular phase or lengthening of the luteal phase were observed. Suppression of plasma testosterone by prednisone was maximal after 2 months of treatment, while the effect on the phases of the menstrual cycle was progressive with duration of treatment. The effects of prednisone at daily dosages of 7.5 or 10 mg were not significantly different. These results suggest that prednisone therapy in hyperandrogenic women exerts an effect on both phases of the menstrual cycle, possibly related to suppression of plasma testosterone levels.

Adult↗

Partial purification and characterization of DNA from the human X chromosome.

Human X chromosome DNA was partially purified from a mouse-human hybrid cell line containing a single human chromosome, the X. Enrichment of such DNA was accomplished by two sequential reassociations of radiolabeled hybrid cell DNA with large excesses of mouse DNA. Unreassociated hybrid cell DNA was used as a probe for human X chromosome sequences. The human-specific fraction of probe DNA CONTAINED THREE COMPONENTS. Two of these reassociated to human DNAs at rates proportional to the number of X chromosomes present. These two components were thus localized to the X chromosome. One of these X-specific components, representing about 80% of human-specific probe DNA, consisted of single copy or very low order reiterated DNA. The second X-specific component, representing about 10% of human-specific probe DNA, was about 20-30 times more reiterated. The remaining 10% of human-specific probe DNA, although derived from the X chromosome, reassociated to human DNAs at a rate independent of the number of X chromosomes present. This component was thus homologous to autosomal as well as X chromosome DNA. The probe DNA accounts for approximately half of the human X chromosome, suggesting that the remainder may have homology with mouse DNA.

Animals↗