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Biomedical subjects

M A Harris

Publications and source records attributed to M A Harris.

At least 109 records · Page 6Linked to original sources

Structural characterization of the rat seminal vesicle secretion II protein and gene.

The gene encoding rat seminal vesicle secretion II (SVS II) protein has been cloned from a rat genomic DNA library using a cDNA probe generated from rat dorsal prostate androgen-dependent mRNA. The cloned 7.3-kilobase pair genomic fragment contains approximately 5000 base pairs (bp) of the 5'-flanking region and the entire coding region of the SVS II protein within two exons. A sequence of 4156 bp of the rat SVS II gene has been determined, including 2037 bp of the 5'-flanking region, exon 1 (95 bp), intron 1 (236 bp), exon 2 (1171 bp), and 614 bp of the 3'-flanking region. The 5'-flanking region contains three conserved elements found in other seminal vesicle secretion genes (SVS IV-VI proteins) within 250 bp of the transcription start site as well as a glucocorticoid response element at position -314 in the SVS II gene. The first exon encodes a 22-amino acid leader peptide plus the first 2 amino acids of the secreted protein. The second exon encodes the remaining amino acids in the SVS II protein sequence. The mature protein contains 392 residues and has an Mr of 43,116. Concomitant with the gene analysis, the rat SVS II protein was purified to homogeneity, and 333 residues (85%) of the amino acid sequence were determined by automated Edman degradation. The DNA-deduced sequence and that determined by direct analysis of the protein are in complete agreement. The blocked NH2-terminal amino acid was identified as pyroglutamic acid by mass spectrometry and aminopeptidase digestion. A 13-residue structure with the consensus sequence GSQLKSFGQVKSS is repeated 13 times within the SVS II protein and appears to be involved in the formation of the rat copulatory plug via a transglutaminase reaction cross-linking glutamine and lysine residues. Overall, the SVS II protein sequence exhibits little structural relatedness to any other known protein sequence; however, some similarity can be found between the 13-residue repeat and another repeating structure and apparent transglutaminase substrate in the guinea pig seminal vesicle clotting protein.

Amino Acid Sequence↗

Characterization of the hamster DDT-1 cell aFGF/HGBF-I gene and cDNA and its modulation by steroids.

Syrian hamster DDT-1 cells are derived from smooth muscle of the ductus deferens. DDT-1 cell growth is increased by the addition of testosterone (T). Acidic fibroblast growth factor (aFGF) or basic fibroblast growth factor (bFGF) also known as heparin binding growth factor I and II (HBGF-I and HBGF-II) can replace T in the stimulation of growth in these cells. This phenomenon is correlated with testosterone's ability to elevate aFGF/HBGF-I mRNA. The increase steady-state levels of aFGF/HBGF-I mRNA were documented by northern blots and by in situ hybridization. Using a 520 bp human aFGF/HBGF-I cDNA probe, a genomic clone with a 38 kb DNA insert was isolated from a cosmid library. By restriction enzyme analysis and southern hybridization, it was determined that there are three coding exons. DNA sequence analysis showed all of the coding region and 3' noncoding sequences were on this clone. A 5' noncoding exon not in the 38 kb insert is indicated, based on the cDNA sequences and genomic sequences of aFGF/HBGF-I's from hamster DDT-1 cells and several other species. The cDNA for hamster aFGF/HBGF-I was isolated from a DDT-1 lambda gt11 library and sequenced. Comparison of the coding region of aFGF/HBGF-I from four species shows a greater than 90% conservation of amino acid sequence.

Amino Acid Sequence↗

The perceived self-competence of adolescents with insulin-dependent diabetes mellitus: deficit or strength?

Two studies were conducted in an attempt to replicate an earlier finding of self-esteem deficits in adolescent girls with early onset of insulin-dependent diabetes mellitus (IDDM). Participants in Study 1 were 139 adolescents with IDDM who completed the Perceived Competence Scale for Children (Harter, 1979). A 2 (gender) X 2 (group: age of IDDM onset: early vs. late) multivariate analysis of variance (MANOVA) did not reveal a significant interaction effect. Study 2 included 136 adolescents (104 adolescents with IDDM and 32 physically healthy adolescents) who completed the Self-Perception Profile for Children (Harter, 1985). A 2 (gender) X 3 (early IDDM onset, late IDDM onset, physically healthy control) MANCOVA, controlling for the effects of social class and adolescent age, also indicated no significant interaction effect. Thus, we found no differences in self-esteem based on age at disease onset and gender in two independent samples of youths with IDDM. In Study 2, significant gender and group effects were revealed, but when these findings are compared with normative data and data from our physically healthy sample, the results suggest that the youths with IDDM were functioning within the normal range on self-esteem. The importance of these findings in regard to the deficit versus adaptation models of chronic illness is discussed.

Adaptation, Psychological↗

Pregnancy-associated deaths due to AIDS in the United States.

From 1981 to 1988, eighty percent of all women with the acquired immunodeficiency syndrome (AIDS) reported to the Centers for Disease Control were of reproductive age. Six pregnancy-associated deaths due to AIDS in this country have been reported in the medical literature. We identified 20 unpublished cases of women who died of AIDS during or within one year after termination of pregnancy. Analysis showed that these women were mostly black or Hispanic, half were intravenous drug abusers, and most died of Pneumocystis carinii pneumonia. Each pregnancy had an obstetric complication, primarily preterm delivery. The interval between diagnosis of AIDS and the death of these women ranged from one day to 15 months, with a mean interval of 113 days. Multiple reporting sources increased case detection and should be used for future investigations. Prospective case-control studies are needed to determine any further relationship between pregnancy complications and AIDS.

Acquired Immunodeficiency Syndrome↗

Coping styles in youths with insulin-dependent diabetes mellitus.

The relationships between two coping styles (i.e., use of personal and interpersonal resources; ventilation and avoidance) and two health outcomes (i.e., adherence and metabolic control) were evaluated in 135 youths with insulin-dependent diabetes mellitus (IDDM). Individual characteristics (i.e., age, duration of illness) and contextual variables (i.e., stress, family relations) were used to predict coping styles. Poor adherence to treatment, older adolescent age, and long duration of IDDM were correlated with ventilation and avoidance coping. Youths with short duration of IDDM were more likely to cope through the use of personal and interpersonal resources, although this strategy was not associated with health outcomes. A multiple regression analysis indicated that high ventilation and avoidance coping was predicted by high stress, low family cohesion, and older adolescent age. In addition, the interaction between family adaptability and duration of IDDM significantly predicted ventilation and avoidance coping.

Adaptation, Psychological↗

Family system variables and the health status of adolescents with insulin-dependent diabetes mellitus.

This study investigated the associations between important dimensions of family relations and the metabolic control of adolescents with insulin-dependent diabetes mellitus (IDDM). Participants were 94 intact families (mother, father, and adolescent) of adolescents with IDDM. Metabolic control was determined by the adolescents' level of HbA(1c), and family relations were assessed with the Marital Adjustment Scale and the Family Adaptability and Cohesion Evaluation Scales-II. Although zero-order correlations showed that good metabolic control was associated with high family cohesion, family flexibility, and high marital satisfaction, hierarchical regression analyses revealed that these associations were considerably attenuated when participant demographic variables, especially the duration of IDDM, were controlled. Follow-up analyses showed that the associations between family relations and metabolic control were mediated by the duration of IDDM. Under conditions of short duration, there were strong associations between family relations and metabolic control. As duration lengthened, however, these associations decreased substantially. These results suggest that the associations between family relations and health are relatively complex in this sample of adolescents with IDDM.

Adaptation, Psychological↗

Errors in low flow oxygen delivery systems.

Accurate delivery of low flow oxygen is essential for the management of infants with chronic respiratory failure. Twenty-seven examples of one low flow oxygen meter were tested. Measured flows were found to differ greatly from indicated settings, particularly at 250 mL/min settings. Knowledge of such errors as well as improved quality control are essential for appropriate management of oxygen therapy.

Oxygen Inhalation Therapy↗

An evaluation of the role of relaxin in the penetration of cervical mucus by spermatozoa.

Relaxin-like immunoreactivity was measured in seminal plasma from men who were separated into two groups, on the basis of a previous positive or negative result in a postcoital cervical mucus penetration test. There was no difference in the relaxin concentration between the groups. The effect of exogenous porcine relaxin (0, 10 or 100 ng/ml) on human cervical mucus penetration in vitro by washed human spermatozoa was studied using a capillary tube preparation. In the positive postcoital test group the highest relaxin concentration (100 ng/ml) tended to inhibit cervical mucus penetration, although this effect was only significant for one of the parameters measured (number of spermatozoa penetrating to the 10-mm mark). The same trend was apparent for the negative postcoital test group, but no differences were significant. The results are in direct contrast to previous reports that relaxin can stimulate human spermatozoa motility and cervical mucus penetration.

Cervix Mucus↗

Steroid potentiation of beta-adrenergic-sensitive adenylate cyclase in rabbit ciliary processes.

Dexamethasone (3.3 X 10(-8) M) potentiated 1-isoproterenol-stimulated adenylated cyclase activity in vitro in rabbit ciliary process epithelial membrane preparations. The ka for isoproterenol stimulation of the cyclase was 5 X 10(-7) M in control membranes, 2.5 X 10(-9) M in membranes preincubated with dexamethasone, and 6 X 10(-8) M with corticosterone. No change was observed in basal adenylate cyclase activity. Changes in enzyme activity at maximally stimulating levels of isoproterenol were not consistently different. Dose response to corticosterone in the presence of 10(-7) M 1-isoproterenol shows maximum effect at 6.6 X 10(-8) M corticosterone.

Adenylyl Cyclases↗

Desensitization to topical epinephrine in the rabbit eye: attenuation by dexamethasone.

Desensitization of ocular adrenergic receptors was examined in vivo in albino rabbit eyes. Repeated topical administration of 2.0% l-epinephrine bitartrate (equivalent to 1.1% free base) to the rabbit eye resulted in the loss of ocular hypotensive response on the second day of daily or twice-daily treatment. Concurrent topical administration of dexamethasone phosphate (0.1%) prolonged the pressure-lowering effect of 2.0% l-epinephrine for up to 5 days. Loss of pressure-lowering response was accompanied by 100% inhibition of ciliary process beta-adrenergic-sensitive adenylate cyclase activity following 6 days of topical administration of l-epinephrine; inhibition of c-AMP synthesis was attenuated by dexamethasone (27% decrease in activity after 6 days of treatment). The data suggest that modulation of epinephrine-induced desensitization by corticosteroids in the rabbit eye is associated with stabilization of beta-adrenergic-sensitive adenylate cyclase activity.

Adenylyl Cyclases↗

Treatment of advanced breast cancer with two doxorubicin-containing regimens.

The Georgetown University Hospital experience in the treatment of advanced breast cancer using either a combination of doxorubicin (adriamycin) and vincristine (AV) or adriamycin and mitomycin-C (AM) is presented. Of 74 previously treated patients with advanced breast cancer, 50 patients were given AV and 24 patients were given AM. Both groups were comparable in regard to number of disease sites, age, prior radiation therapy, disease-free interval after mastectomy, duration of treatment, and estrogen-receptor status. The response rates were 32% and 25% with AV and AM combinations, respectively. Achievement of response was not related to menopausal or estrogen-receptor status. Median time to disease progression was 7.0 and 9.6 months for AV and AM, respectively. Median survivals were not statistically different (9.7 months for AV and 11.1 months for AM). Life-table analysis for responders versus nonresponders within each regimen and between responders in either regimen revealed no statistical differences. Duration of response for each regimen was also equivalent. Toxicity was mild and similar to previous reports using these drugs. However, myelosuppression was significantly greater for premenopausal than postmenopausal patients in the AV group. The possible reasons for this are discussed. Both AM and AV are well-tolerated regimens which provide equivalent but limited response rates, duration of response, and median survival in previously treated women with advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of platelet factor 4 (PF4) on assays of plasma heparin.

Platelet factor 4 (PF4) is a potent antiheparin in vitro. In view of the large amount of PF4 secreted from platelet alpha-granules during routine blood collection and processing techniques, the potential significance of this release was investigated using three measurements of heparin activity: the activated partial thromboplastin time (aPTT), the thrombin time, and factor Xa inactivation using the chromogenic substrate S2222 for assay of factor Xa. The results demonstrate that purified PF4 neutralizes heparin activity when added in increasing amounts to normal platelet-poor plasma containing a fixed concentration of commercial porcine gut mucosal heparin. This effect was seen when assaying heparin activity by all three methods. In addition, when heparin was added in increasing concentrations to pooled plasma samples that were collected from normal volunteers, there was neutralization of heparin activity in blood samples collected by routine citrate anticoagulation (CIT60) in comparison to blood samples collected simultaneously with platelet secretion inhibiting agents added to the anticoagulant (CIT+). This effect was seen when assaying heparin by the aPTT and thrombin time. These data confirm that both purified and secreted PF4 have significant antiheparin activity when heparin is added in vitro to normal plasma. Neutralization of circulating heparin by PF4 secreted during blood collection from anticoagulated patients could result in underestimation of the actual in vivo heparin concentration. In order to evaluate the significance of this effect, purified PF4 was added to plasma collected from heparinized patients and again PF4 neutralized heparin activity. This was seen, however, only when heparin activity was measured by the thrombin time or Xa inactivation assays. There was minimal shortening of the aPTT when PF4 was added in final concentrations up to 1000 ng/ml. When blood samples were simultaneously collected from anticoagulated patients by both routine and special collection methods, these results were confirmed. There was a significant difference between heparin activities measured in the CIT+ (secreted PF4 58 ng/ml) and CIT60 (secreted PF4 1074 ng/ml) plasma samples by both thrombin time and Xa inactivation. There was no difference, however, in the aPT when both types of plasma samples were simultaneously collected and assayed for each anticoagulated patient. This suggests that there may be circulating heparin fractions which can prolong the aPTT but which do not interact with PF4.(ABSTRACT TRUNCATED AT 400 WORDS)

Factor X↗

Disseminated Kaposi's sarcoma in pregnancy: a manifestation of acquired immune deficiency syndrome.

The first case of acquired immune deficiency syndrome (AIDS) in pregnancy is reported. The patient, a drug addict, presented with lymphadenopathy, pulmonary infiltrates, and skin lesions of Kaposi's sarcoma, a tumor rarely found in young women in this country. The helper T-lymphocyte to suppressor T-lymphocyte ratio showed the profound inversion characteristic of this cell-mediated immune deficiency disease. Chemotherapy, a combination of doxorubicin, bleomycin, and vinblastine, was initiated during pregnancy. A growth-retarded infant was delivered vaginally. At four months of life, the infant had no apparent evidence of immune deficiency. Transplacental transmission of AIDS has not, as yet, been demonstrated. The social factors, clinical and laboratory features, and the controversies surrounding this new disease are discussed.

Acquired Immunodeficiency Syndrome↗