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Biomedical subjects

S Bass

Publications and source records attributed to S Bass.

At least 19 recordsLinked to original sources

Serum cortisol concentration and testosterone to cortisol ratio in elite prepubescent male gymnasts during training.

Serum cortisol concentrations and testosterone:cortisol concentration ratios of eight prepubescent elite male gymnasts (mean age 10 years 11 months) and 11 controls (mean age 11 years 1 month) were examined during 5 consecutive training days. During this period, the gymnasts trained 3 h each day with moderate intensity mobility, strength and skill exercises while the controls were relatively sedentary. Blood samples were taken from all the boys in both groups before (1630 hours) and 30 min after (2000 hours) training on 4 days. Serum cortisol concentrations of the gymnasts were not significantly different from those of the controls throughout the experiment. Serum cortisol concentrations of both groups were significantly larger (P < 0.05) at 1630 hours than at 2000 hours, indicating that cortisol secretion followed the typical adult circadian change, seemingly unaltered by training. However, there was a significant decrease (P < 0.05) in the testosterone:cortisol ratio of the gymnasts when compared with controls from day 1 to day 3. After a rest on day 4 the testosterone: cortisol ratio of the gymnasts significantly increased (P < 0.05) but the ratio of the control group also increased indicating that there may have been some day-to-day change by factor(s) other than training. The most obvious factor which may have accounted for the unresponsiveness of serum cortisol concentration to the gymnastics training was that the exercise intensity was too low. However, several days of the training seemed to reduce the anabolic to catabolic balance but further experiments are needed to confirm this finding.

Child

Youth as a prognostic factor in carcinoma of the cervix: a matched analysis.

A matched analysis comparing 250 patients less than 35 years old with squamous cell cancer of the cervix treated between 1971 and 1981 to a randomly selected group matched on treatment who were greater than 35 years old was performed. A chart review that focused on important prognosticators for survival and progression-free interval was performed. The groups were found to be similar for the important prognosticators. Overall survival and progression-free intervals were plotted using Kaplan-Meier curves and demonstrated that for advanced stages, younger patients were less likely to survive and more likely to recur. Cox proportional-hazard analyses were performed, looking at important prognosticators of survival and progression-free interval. Age, stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of survival, while stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of progression-free interval. The plot of relative hazard by stage of younger versus older patients showed an interaction between age and stage that merits further exploration.

Adolescent

Comparative biodisposition and metabolism of 14C-(+/-)-fenfluramine in mouse, rat, dog and man.

1. The comparative metabolism of fenfluramine was investigated in mouse, rat, dog and man following a single oral dose of 14C-(+/-)-fenfluramine hydrochloride (1 mg/kg), and also in rat after eight consecutive 12-h subcutaneous doses (24 mg/kg). 2. Main route of excretion of radioactivity in all species and at all doses was into urine (> 80%), with only minor amounts of radioactivity found in faeces. 3. From all species examined a total of 11 metabolites were observed in urine and plasma by t.l.c. and h.p.l.c. analysis and no metabolite was present in the plasma which was not present in urine. 4. All species dealkylate fenfluramine to the active metabolite norfenfluramine, to a relative greater or lesser extent, with plasma metabolic ratios (norfenfluramine/fenfluramine) showing inter-animal variation (rat >> dog >> mouse = man). 5. These differences are due to the efficient deamination of both compounds to polar inactive metabolites in man, with less dealkylation and lower plasma levels of norfenfluramine compared with the other species studied. 6. In conclusion, major species differences in the metabolism of (+/-)-fenfluramine, both qualitative and quantitative were observed, and no one species had a similar metabolic profile to that found in man.

Animals

Five-year survival in patients given intra-arterial chemotherapy prior to radiotherapy for advanced squamous carcinoma of the cervix and vagina.

Five-year survival studies in patients with advanced gynecologic pelvic malignancy treated with intra-arterial chemotherapy followed by radiotherapy have not been reported in the literature. Forty-six evaluable patients entered into a study between 1981 and 1985 at the University of Texas-M.D. Anderson Cancer Center were reviewed for follow-up. Two patients were FIGO (International Federation of Gynecology and Obstetrics) Stage IIB cervical cancer, thirty-one patients were Stage III cervical cancer, seven patients were Stage IVA cervical cancer, and six patients were unstaged, cut-through cervical cancer, or primary vaginal carcinoma with bulky tumor volume. Seventeen patients had evidence of obstructive uropathy by intravenous pyelogram. Pretreatment lymphangiogram was carried out in 32 patients, 14 of whom were positive for pelvic lymph node involvement. Forty-four patients had received no prior therapy before initiating intra-arterial chemotherapy. Thirty-five (76%) of the patients responded to locally infused pelvic intra-arterial chemotherapeutic agents consisting of mitomycin-C, bleomycin, and cisplatin. Vincristine was given peripherally by intravenous access. There were 24 (52%) partial responders, 11 (24%) complete responders, and 11 (24%) nonresponders. Two (4%) patients progressed during treatment, while twenty-six (57%) patients relapsed after receiving chemotherapy followed by radiotherapy. Three additional patients died from treatment-related causes, one secondary to renal failure, one to massive pulmonary embolus, and one from a combination of pulmonary toxicity secondary to bleomycin and sepsis. Three of fifteen patients in complete remission died from unrelated causes with no evidence of disease. The 5-year survival rate for the study group was 30%, with a median survival duration of 18 months.

Adult

Prognostic indicators for invasive carcinoma of the vulva.

Three hundred sixty-five patients with invasive squamous cell carcinoma of the vulva have been treated at M.D. Anderson Cancer Center between 1944 and 1990. We undertook a rigorous review of the medical records, and a Cox proportional hazards model was applied to examine predictors of both failure to survive and recurrence. Significant predictors of both failure to survive and recurrence included tumor size, clinical stage, therapy aim, pelvic or inguinal nodal metastases, and positive margins. We then undertook an analysis of Stage I and II lesions treated with a curative aim to see if there was a difference in survival or in disease-free interval between those patients treated with radical vulvectomy and those treated with radical wide local excision. There was no survival advantage from the radical vulvectomy procedure. We conclude that careful selection may allow us to choose some patients for less radical procedures.

Carcinoma

The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. II. Inhibition of IL-2 production.

Culture supernatants from concanavalin-A (con-A)-activated peripheral blood lymphocytes from healthy controls grown in the presence of sera from 20 patients 24 hours and 1 week after acute myocardial infarction (AMI) were tested for their mitogenic activity and for the presence of interleukin-2 (IL-2). Binding of exogenous IL-2 to activated lymphocytes from 10 patients was also determined. In supernatants prepared in the presence of patients' as compared to control sera, a significantly decreased mitogenic activity and IL-2 content were found. The mitogenic activity and IL-2 content in culture supernatants prepared with patients' sera collected 24 hours after the AMI (AMI I) and one week thereafter (AMI II) were significantly suppressed, and the degree of suppression in the 24-hour sera was significantly higher than in those collected after one week. No significant differences were observed in the binding capacity to exogenous IL-2 of activated patients' and control lymphocytes. The possibility is that immunosuppressive factors in the patients' sera, including cortisol, may suppress the patients' immune response acting through inhibition of IL-2 production.

Aged

The effect of serum from patients with acute myocardial infarction on in vitro lymphocyte reactivity. I. Inhibition of mitogen stimulation.

Sera from 20 patients obtained within 24 hours and one week after acute myocardial infarction (AMI) were tested for their immunomodulating effect on concanavalin-A (con-A) stimulated lymphocyte cultures from 11 healthy unrelated donors. Individual control sera from 21 healthy donors and 5 pools of control sera were used for comparison. Cortisol levels were tested in patients' and controls' sera. A significantly higher suppressive effect was seen in the presence of patients' sera taken at 24 hours than corresponding sera taken one week later. However, the suppressive effect after one week was increased as compared to control sera. A significant correlation between the degree of suppression and the cortisol level in corresponding sera was observed. An increased immunosuppression was observed with increased cortisol levels.

Adjuvants, Immunologic

Zinc mediation of the binding of human growth hormone to the human prolactin receptor.

Human growth hormone (hGH) elicits a diverse set of biological activities including lactation that derives from binding to the prolactin (PRL) receptor. The binding affinity of hGH for the extracellular binding domain of the hPRL receptor (hPRLbp) was increased about 8000-fold by addition of 50 micromolar ZnCl2. Zinc was not required for binding of hGH to the hGH binding protein (hGHbp) or for binding of hPRL to the hPRLbp. Other divalent metal ions (Ca2+, Mg2+, Cu2+, Mn2+, and Co2+) at physiological concentrations did not support such strong binding. Scatchard analysis indicated a stoichiometry of one Zn2+ per hGH.hPRLbp complex. Mutational analysis showed that a cluster of three residues (His18, His21, and Glu174) in hGH and His188 from the hPRLbp (conserved in all PRL receptors but not GH receptors) are probable Zn2+ ligands. This polypeptide hormone.receptor "zinc sandwich" provides a molecular mechanism to explain why nonprimate GHs are not lactogenic and offers a molecular link between zinc deficiency and its association with altered functions of hGH.

Amino Acid Sequence

The human growth hormone receptor. Secretion from Escherichia coli and disulfide bonding pattern of the extracellular binding domain.

A gene fragment encoding the extracellular domain of the human growth hormone (hGH) receptor from liver was cloned into a plasmid under control of the Escherichia coli alkaline phosphatase promoter and the heat-stable enterotoxin (StII) signal peptide sequence. Strains of E. coli expressing properly folded hGH binding protein were identified by blotting colonies with 125I-hGH. The E. coli strain capable of highest expression (KS330) secreted 10 to 20 mg/liter of culture of properly processed and folded hGH receptor fragment into the periplasmic space. The protein was purified to near homogeneity in 70 to 80% yield (in tens of milligram amounts) using ammonium sulfate precipitation, hGH affinity chromatography, and gel filtration. The unglycosylated extracellular domain of the hGH receptor has virtually identical binding properties compared to its natural glycosylated counterpart isolated from human serum, suggesting glycosylation is not important for binding of hGH. The extracellular binding domain codes for 7 cysteines, and we show that six of them form three disulfide bonds. Peptide mapping studies show these disulfides are paired sequentially to produce short loops (10-15 residues long) as follows: Cys38-Cys48, Cys83-Cys94, and Cys108-Cys122. Cys241 is unpaired, and mutagenic analysis shows that the extreme carboxyl end of the receptor fragment (including Cys241) is not essential for folding or binding of the protein to hGH. High level expression of this receptor binding domain and its homologs in E. coli will greatly facilitate their detailed biophysical and structural analysis.

Amino Acid Sequence

Hormone phage: an enrichment method for variant proteins with altered binding properties.

Human growth hormone (hGH), a 191 residue protein containing two disulfide bonds, was fused to the carboxyl-terminal domain of the gene III protein, a minor coat protein exposed at one end of the filamentous phage M13. The gene fusion was cloned into a plasmid containing origins of replication for Escherichia coli and filamentous phage and was packaged into phagemid particles upon infection by an M13KO7 helper phage. Transcription of the hGH-gene III fusion was controlled so that usually no more than one copy of the fusion protein was displayed along with the four copies of the wild-type gene III protein. The hGH-gene III fusion protein was properly folded, as judged by reactivity with six hGH monoclonal antibodies whose epitopes are sensitive to the folded conformation of hGH. Moreover, the hGH-gene III phagemid particles were enriched over 5000-fold from non-hGH phage, and 8-fold from a mutant hGH phagemid following a single hGH-specific elution step from hGH receptor-coated beads. The hGH phagemid should be useful for isolating new receptor binding mutants of hGH. More generally, this expression system may allow other large proteins with discontinuous binding epitopes to be displayed, and binding selections applied to their mutated gene III fusions on filamentous phage.

Base Sequence

Acquired immunodeficiency syndrome (AIDS)-free time after human immunodeficiency virus type 1 (HIV-1) seroconversion in homosexual men. Multicenter AIDS Cohort Study Group.

To estimate the time interval between human immunodeficiency virus type 1 (HIV-1) seroconversion and acquired immunodeficiency syndrome (AIDS) diagnosis in homosexual men, prospective incident cohorts are difficult to obtain and, if assembled, provide few events owing to the long incubation time. Although seroprevalent cohorts are numerous in size and events, the information is limited due to the unknown times since seroconversion. To combine the information provided by 1,628 seroprevalent men (304 AIDS cases) and 233 seroconverters (12 AIDS cases) being followed in a multicenter study since 1984, the postseroconversion changes in hematologic variables occurring in the incident cohort were used to develop a model that allowed for the imputation of the unknown times since seroconversion for the seroprevalent cohort. Nonparametric life table methods incorporating truncation and censoring were applied for the estimation of the probability distribution of the AIDS-free time after seroconversion. The precision of the estimates was evaluated using bootstrap methods. The analysis suggested that AIDS is unlikely (less than 0.5%) in the first year; 78% of seropositive homosexual men remain AIDS-free 60 months after seroconversion; and the AIDS incidence increases for months 12-36 and levels off at 38 per 1,000 person-semesters for months 42-60. The nonparametric estimate of the incidence rate suggests a median AIDS-free time of 11 years, which is longer than previous estimates based on parametric models.

Acquired Immunodeficiency Syndrome

Mutant Trp repressors with new DNA-binding specificities.

Oligonucleotide-directed mutagenesis of the codons for glutamine-68 (Gln68), lysine-72 (Lys72), isoleucine-79 (Ile79), alanine-80 (Ala80), and threonine-81 (Thr81) of the Escherichia coli trpR (tryptophan aporepressor) gene was used to make mutant repressors with each of 36 different amino acid changes. Mutant repressors were tested for binding to each member of a set of 28 different operators closely related to the consensus trp operator. Of the 36 mutant repressors, 11 bind a subset of the 28 operators; 5 of these have new binding specificities. These new specificities indicate that the hydroxyl group of Thr81 makes a specific contact with one of the four critical base pairs in a trp operator half-site, and the methyl group of Thr81 determines specificity at a second, critical base pair. The Trp repressor does not use the first two amino acids of its "recognition alpha-helix," Ile79 and Ala80, to make sequence-specific DNA contacts, and interacts with its operator in vivo in a way fundamentally different from the way that phage lambda repressor, lambda Cro protein, and coliphage 434 repressor contact their respective binding sites.

Alanine

Acquired immune deficiency syndrome: implications for optometry and the public health.

Recognized in 1981, acquired immune deficiency syndrome or AIDS has become a worldwide epidemic. HIV virus is believed to be the causative agent and acts primarily upon T-helper lymphocytes and nerve tissue, damaging the body's immune system. Ocular and systemic opportunistic infections result. Transmission is primarily by intimate contact with infected blood or semen. The virus has been found in eye tissues and raises questions about safety during eye care delivery, as well as optometry's role as a primary eye care profession.

Acquired Immunodeficiency Syndrome

Presurgical prediction of postsurgical visual acuity in patients with media opacities.

Of the estimated 1 million patients each year in the United States who undergo surgery for media opacities, perhaps 5-10% fail to improve because of pre-existing, undiagnosed retinal and/or optic nerve disease. In this paper, the standard presurgical evaluation (case history, visual acuity, refraction, pupillary response testing, biomicroscopy, ophthalmoscopy, tonometry, visual fields and color vision) and the supplementary presurgical evaluation (entoptic phenomena appreciation, ophthalmic ultrasonography, fluorescein angiography, laser interferometry, potential acuity meter, visual evoked potential, electroretinography, contrast sensitivity and hyperacuity measurements) are reviewed.

Cataract

DNA specificity determinants of Escherichia coli tryptophan repressor binding.

We have analyzed the sequence-specific interaction between the Escherichia coli tryptophan (Trp) repressor and its operator using challenge phage vectors. These phages, derivatives of Salmonella phage P22 that have substitutions of synthetic, symmetric trp operators for the P22 mnt operator, provide a genetic assay for DNA binding in vivo. Phages carrying operators that retain the determinants of Trp repressor binding efficiently lysogenize cells producing repressor; in contrast, phages with operators missing critical determinants kill such hosts. The binding determinants revealed by this assay corroborate a simple docking model for the Trp repressor-operator interaction postulated from the repressor crystal structure, and account for both the specificity of repressor binding and the ability of Trp repressor to recognize multiple, tandem DNA sites.

Bacterial Proteins

General selection for specific DNA-binding activities.

We present a general strategy for the selection of bacterial clones that express DNA-binding activities corresponding to particular DNA recognition sites. The selection uses a "challenge phage" vector, P22 Kn9 arc-amH1605, into which is substituted a synthetic DNA-binding site for a site that controls transcription of the P22 antirepressor (ant) gene. Constitutive synthesis of antirepressor channels a challenge phage into lytic development and efficiently kills an infected host, unless the substituted site is bound by a specific protein; in this case, the challenge phage prefers lysogenic development, and the host survives and acquires an antibiotic-resistance phenotype. Infections with challenge phages carrying the E. coli Lac operator, phage lambda OL1 operator, or synthetic, "idealized" E. coli Trp and Tn10 Tet operators select clones that express each of the corresponding binding activities. The use of challenge phage vectors may be extended to select clones that express eukaryotic DNA-binding activities.

Base Sequence