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Biomedical subjects

J Stephens

Publications and source records attributed to J Stephens.

At least 55 records · Page 3Linked to original sources

Estrogen receptors are present in human granulosa cells.

Recent studies failed to detect estrogen receptors in primate follicles. This study was initiated to determine whether estrogen receptor (ER) messenger ribonucleic acid (mRNA) is present in human granulosa cells and, further, if functional ER proteins are present. To evaluate the presence of ER, RNA from human granulosa cells obtained at the time of oocyte retrieval for assisted reproduction was extracted, and complementary DNA synthesis was performed by the reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA. Southern blotting was performed and confirmed that the amplified DNA fragment identified in granulosa cells represented ER. By reverse transcriptase-polymerase chain reaction, mRNA for the ER is clearly identified in primary human granulosa cells obtained at the time of oocyte retrieval. To expand these studies and determine whether functional ER were present in human granulosa cells in culture, a simian virus-40-transformed human granulosa cell line was studied. Cells were transfected with a plasmid containing as estrogen response element up-stream from the bacterial reporter gene chloramphenicol acetyltransferase (CAT). In transfected cells, CAT activity is inducible by estradiol if endogenous functional ER are present. In these studies, the transfection analysis confirmed that functional, transcriptionally competent ER are present in a human granulosa cell line, with a 4- to 5-fold enhancement of CAT activity demonstrated after the addition of estradiol compared to that in nonhormone-treated cells. In conclusion, ER mRNA is present in human granulosa cells. Functional ER are also demonstrated in a transformed human granulosa cell line. We hypothesize that low, but biologically significant, amounts of ER protein are present in human granulosa cells, which are not routinely detectable by standard assays.

Blotting, Southern↗

Liver T cell subsets and adhesion molecules in murine graft-versus-host disease.

Murine GVHD across multiple minor histocompatibility barriers (B10.D2 into irradiated BALB/c) results in cell-mediated destruction of bile ducts inside the liver. Similar changes are characteristic of hepatic GVHD in humans following BMT. We have defined the phenotypes of inflammatory cells and the accessory/adhesion molecules expressed in the liver between day 7-14 of murine GVHD. T cells (CD3+) comprised 65% of hepatic inflammatory cells. alpha-beta and gamma-delta cells accounted for 92 and 8%, respectively of hepatic T cells. The percentage of CD4+ cells (29%) was 3 times that of CD8+ cells (11%). Lymphocyte function-associated antigen-1 (LFA-1) was expressed by the majority of inflammatory cells. Thirty per cent of the cells were positive for Mac-1, a differentiation marker of macrophages, large granular lymphocytes, and natural killer cells. Expression of intercellular adhesion molecule-1 and major histocompatibility complex class II (IAd) molecules on bile duct epithelial and portal vein endothelial cells was induced during GVHD. These results suggest that hepatic GVHD is induced by donor alpha-beta T cells through mechanisms that may involve CD4:1Ad and LFA-1:ICAM-1 interactions.

Animals↗

In vitro comparison of the effectiveness of three surface disinfectants.

Choosing a general purpose surface disinfectant for the dental office environment is difficult because of the wide range of products available, varying claims by manufacturers and contradictory reports in the literature regarding product efficacy. This study tested the antimicrobial effectiveness of diluted-for-use O-phenyl-phenol (Omni), didecyl dimethyl ammonium (Basic G) and isopropanol (Virahol). Products were tested for antimicrobial activity at 0, 12 and 24 hours, 3, 6 and 8 days. O-phenyl-phenol demonstrated essentially no antibacterial effect against any of eleven test microorganisms. Didecyl dimethyl ammonium and the isopropanol reagent both demonstrated statistically significant killing activity against all organisms. More importantly, these two products maintained their antimicrobial activity up to 8 days after preparation.

1-Propanol↗

Inhibition of human and murine cytosolic epoxide hydrolase by group-selective reagents.

1. Human and murine cytosolic epoxide hydrolase were inhibited by thiol-, imidazole- and carboxyl-selective reagents. They were not inhibited by amino-, guanido- or activated serine-selective reagents. 2. Murine, but not human, cytosolic epoxide hydrolase was inhibited by N-bromosuccinimide, a tryptophan selective reagent. 3. Based on sequence data from peptides isolated from CNBr digests, human and murine CEH share areas of sequence homology. Of the five unique human CEH CNBr peptides sequenced, three shared common sequences with one of the unique murine CEH CNBr peptides. The human and murine CEH peptides with common sequences had between 64 and 78% sequence identity. 4. A cysteine important for the activity of murine CEH appears not to be in the active site as judged by N-phenylmaleimide inhibition in the presence and absence of either (2S,3S)-2,3-epoxy-3-(4-nitrophenyl)glycidol, a competitive inhibitor, or trans-stilbene oxide, a substrate.

Amino Acid Sequence↗

Ontogeny of the humoral immune response to human immunodeficiency virus type 1 in infants.

In a cohort of infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers, changes in the levels of HIV-1 specific antibodies were measured during the first year of life. In uninfected children, the level of antibodies to six HIV-1 antigens (gp120, p66, p41, p31, p24, and p17) decreased continuously until becoming negative. In contrast, rising levels of one or more specific antibodies were detected in 9 of 12 infected children at a median age of 6 months. At 1 year of age, 8 infants were still asymptomatic and classified as P-1. All had serologic profiles consistent with de novo specific antibody production. In contrast, among the 4 infants who had early disease (class P-2), 3 had no significant rise in antibody to HIV-1. These results indicate that poor immune response, which could result from early infection of the infant, is often associated with rapid clinical progression.

Cohort Studies↗

Metaphase chromosome and nucleoid differences between CHO-K1 and its radiosensitive derivative xrs-5.

The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant isolated from CHO-K1 cells. The radiation sensitivity is associated with a defect in DNA double-strand break rejoining. Chromatin structure also appears altered in xrs-5 cells compared with the parental CHO-K1 cells. Metaphase chromosomes from xrs-5 are more condensed in appearance than CHO-K1 chromosomes. The overcondensed look is not the result of colcemid sensitivity. Electron microscopy studies suggest that xrs-5 metaphase chromosomes have larger loops of chromatin extending out from the chromosome core. There are also differences between CHO-K1 and xrs-5 cells in the size and fluorescence pattern of ethidium bromide-stained nucleoid preparations. These results suggest that there is a fundamental difference between CHO-K1 and xrs-5 in either the organization of the supercoiled loops of DNA attached to the nuclear matrix or in the nature of the proteins that attach the DNA to the matrix. These alterations in chromosome structure may underlie, in part, the radiation sensitivity of xrs-5 cells.

Animals↗

The effects of ketanserin on ventricular ectopic activity in humans.

Ketanserin is a serotonin S2-receptor antagonist that lowers blood pressure and inhibits platelet aggregation. Ketanserin treatment is also associated with prolongation of the corrected QT interval. The recently reported Prevention of Atherosclerotic Complications with Ketanserin (PACK) trial confirmed this prolongation of QT and also revealed a significant excess of deaths in patients receiving ketanserin together with potassium-losing diuretics. The investigators suggested that this excess of deaths may have been attributable to exacerbation of hypokalemia-induced ventricular arrhythmias by the repolarization-prolonging effect of ketanserin. However, drugs that prolong the QT interval may affect ventricular ectopic activity beneficially, and our study was designed to evaluate the effects of ketanserin on ventricular ectopic activity. Twenty patients (18 male, 2 female) aged 42-73 years were studied, each having at least 15 ventricular ectopic beats/hour. The study design was a double-blind, crossover comparison of ketanserin, 40 mg twice daily, and placebo, both given for 1 week. Ventricular ectopic activity was assessed by 48-hour Holter electrocardiogram (ECG) tapes at the end of each treatment period. Ketanserin treatment was associated with prolongation of repolarization, as reflected by the significant mean increases in both QT interval (+30 ms; p less than 0.001) and corrected QT interval (+20 ms; p less than 0.05). The mean overall degree of ventricular ectopic activity, as represented by a score based on the Lown classification, was significantly reduced (p less than 0.05). This was associated with a concordant improvement in the individual indices of ectopic activity. Our results show that ketanserin significantly suppressed ventricular ectopic activity in our normokalemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Perceptions of popularity among a group of high-functioning adults with autism.

The purpose of this study was to determine how a group of adults with autism perceived one another's interpersonal attributes and popularity. Five female and 11 male high-functioning autistic adults, 18-45 years old, participated in a social skills group together for several years. A sociogram and a questionnaire designed to determine perceptions of best looking, most athletic, and most humorous group members were administered to group members and nonhandicapped group leaders. Independent assessments of intelligence and empathy also were taken. Results indicated that perceived attractiveness and sense of humor were correlated with popularity, but group members' assessments of these attributes differed from those of the nonhandicapped group leaders. Differences between group members and group leaders responses and the implications of the results of the study for social skills training with high-functioning autistic adolescents and adults are discussed.

Adolescent↗

A comparison of single doses of lisinopril and enalapril in hypertension.

Sixteen patients with mild to moderate hypertension were studied in a double-blind crossover comparison of single oral doses of lisinopril 10 mg and enalapril 10 mg. Both drugs caused a marked fall in blood pressure (BP) with a clinically useful effect persisting for 24 h postdose and with no significant difference between treatments in this respect. The time to minimum systolic BP was 2 h (95% confidence limits 0-19 h) longer for lisinopril. The fall in ACE activity at 24 h was 18.5 (8.2-28.8) U/l greater for lisinopril. We conclude that, within the limits of this small study, lisinopril appears to be as effective as enalapril in lowering BP and that it may have a slower onset of action that could be clinically valuable.

Adult↗

Tropical epidemiology: a system for continuous demographic monitoring of a study population.

Epidemiologists in many developing countries, where official demographic services are unavailable, have to include some demographic functions in their work. The usual method of documenting a study population for epidemiological research in a developing country consists of three stages: mapping, enumeration and vital registration. This paper considers the last element of this process, detailing the development of a suitable data system and explaining how its implementation using microcomputers and a database management system can help in the creation of an on-line continuous vital registration system for a study population as an epidemiological tool. The issues covered are data collection, entry and analysis, and the advantages of such a system for use in epidemiological research in developing countries are also discussed.

Africa, Western↗

Dose-ranging study of isosorbide-5-mononitrate in chronic congestive heart failure treated with diuretics and angiotensin-converting enzyme inhibitor.

The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Primary oat cell carcinoma of the larynx.

The aggressiveness of small (oat) cell carcinoma of the larynx presents a therapeutic challenge to the oncologist. Since the first description of this type of carcinoma in 1972, 52 patients have been reported in the literature and a variety of treatment regimens have been used. The purpose of this study was to report two new cases and review all previous reports to determine the disease's biological behavior, clinical manifestations, and optimum treatment. Thirty-five percent of the tumors were transglottic, and 27% were supraglottic. Fifty-four percent of patients had regional metastases at initial presentation and 17.6% had distant metastases. The median survival was 10 months for all patients. Patients who were treated with chemotherapy with or without other modalities had the best 2-year survival rates (52.2%). Forty-one percent of patients had regional recurrence only, 12.5% had regional recurrence and distant metastases, and 2% developed distant metastases only. We conclude that patients with oat cell carcinoma of the larynx should be treated with combination chemotherapy and radiation therapy. Surgery is best reserved for persistent and recurrent disease at the primary site and neck.

Adult↗

Relationship between myocardial uptake and actions in heart failure of methyldigoxin.

1 Problems have been encountered in recent years in confirming useful benefit to patients with heart failure and sinus rhythm from acute exposure to digitalis glycosides, though effectiveness of these preparations upon cardiac contractile performance is indisputable. Undesired effects such as those upon systemic vascular resistance have been invoked to explain this. 2 Detailed haemodynamic responses have been studied by cardiac catheterisation in nine such patients for 30 min after intravenous methyldigoxin infusion. Myocardial glycoside uptake was simultaneously assessed. 3 Methyldigoxin uptake by the heart was rapid, passing its peak within 20 min, and was followed by substantial elution. 4 A small progressive and significant increase in cardiac output was observed, though left ventricular filling pressures were not significantly reduced after methyldigoxin. Cardiac contractile function as assessed by left ventricular maximum dP/dt, measured in six patients, showed consistent improvement.

Cardiac Catheterization↗