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Biomedical subjects

S Simpson

Publications and source records attributed to S Simpson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Components required for in vitro cleavage and polyadenylation of eukaryotic mRNA.

We have studied in vitro cleavage/polyadenylation of precursor RNA containing herpes simplex virus type 2 poly A site sequences and have analyzed four RNA/protein complexes which form during in vitro reactions. Two complexes, A and B, form extremely rapidly and are then progressively replaced by a third complex, C which is produced following cleavage and polyadenylation of precursor RNA. Substitution of ATP with cordycepin triphosphate prevents polyadenylation and the formation of complex C however a fourth complex, D results which contains cleaved RNA. A precursor RNA lacking GU-rich downstream sequences required for efficient cleavage/polyadenylation fails to form complex B and produces a markedly reduced amount of complex A. As these GU-rich sequences are required for efficient cleavage, this establishes a relationship between complex B formation and cleavage/polyadenylation of precursor RNA in vitro. The components required for in vitro RNA processing have been separated by fractionation of the nuclear extract on Q-Sepharose and Biorex 70 columns. A Q-Sepharose fraction forms complex B but does not process RNA. Addition of a Biorex 70 fraction restores cleavage activity at the poly A site but this fraction does not appear to contribute to complex formation. Moreover, in the absence of polyethylene glycol, precursor RNA is not cleaved and polyadenylated, however, complexes A and B readily form. Thus, while complex B is necessary for in vitro cleavage and polyadenylation, it may not contain all the components required for this processing.

Base Sequence↗
PubMed1988

Effect of methacholine induced bronchoconstriction on the pulmonary distribution and plasma pharmacokinetics of inhaled sodium cromoglycate in subjects with normal and hyperreactive airways.

Inhalation treatment may be less effective in the presence of bronchoconstriction because of the reduced penetration of drugs into the airways. The effect of bronchoconstriction on the lung deposition and plasma pharmacokinetics of inhaled sodium cromoglycate was examined. Ten subjects attended the laboratory on three occasions. On the first occasion a bronchial provocation test was performed to determine the concentration of methacholine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20). On the two subsequent occasions subjects inhaled either saline or their PC20 methacholine, followed five minutes later by an aerosol containing sodium cromoglycate and stannous phytate labelled with technetium-99m. Twenty minutes later a gamma emission lung scan was performed to determine the intrathoracic deposition of the nebulised aerosol. The central:peripheral (C:P) ratio of lung deposition was then calculated. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for four hours. Methacholine led to a 23.4% (SEM 0.6%) lower FEV1 and a 2.8 times higher C:P ratio than those observed after saline. There was a direct correlation between log PC20 methacholine and the increase in the C:P ratio (r = 0.81). Despite these changes with methacholine, the plasma pharmacokinetics of inhaled sodium cromoglycate were not significantly different after methacholine and after saline, except that the maximum concentration achieved (Cmax) was increased. These observations suggest that the area of cromoglycate deposition and the anatomical site are less important in determining the plasma pharmacokinetics of cromoglycate than is the total dose delivered to the lung.

Administration, Inhalation↗
PubMed1987

Human papillomavirus type 16 DNA from a vulvar carcinoma in situ is present as head-to-tail dimeric episomes with a deletion in the non-coding region.

A number of genital cancer biopsy samples were screened for the presence of human papillomavirus type 16 (HPV-16) DNA sequences. One of these samples (a vulvar carcinoma in situ) was found to contain more than 100 copies of HPV-16 DNA sequences per cell. Using this tumour DNA, a genomic library was constructed in bacteriophage lambda and the library was screened for recombinant phage containing HPV-16 sequences. Five recombinant phage clones were isolated and their DNA was analysed by restriction endonuclease digestion and blot hybridization. All five recombinants contained two copies of the HPV-16 genome present in a head-to-tail arrangement. The data are consistent with the presence of HPV-16 sequences in the tumour DNA arranged as genomic dimers in a circular episomal configuration. The HPV-16 genomes contained a deletion within the non-coding region, a region which includes the viral origin of DNA replication and transcriptional control sequences. Possible consequences of this deletion for viral replication and transcription are discussed.

Base Sequence↗
PubMed1987

Nutrition and hydration: relationship to preterm myometrial contractility.

Although the mechanisms responsible for the onset of preterm labor in human pregnancy are unclear, animal studies have demonstrated that decreased nutrient intake is associated with increased uterine prostaglandin F metabolite production and spontaneous uterine contractions. The purpose of this study was to assess the association of maternal nutrition and dehydration with preterm uterine contractility. Pregravid weight-for-height, pregnancy weight gain at 30 weeks' gestation, urine specific gravity, ketonuria, and dependent and generalized edema were measured in 30 women who had preterm uterine contractions and in 30 women matched for race, gestational age, socioeconomic status, and smoking who reported no symptoms of preterm contractility. Data were analyzed with the paired-difference t test, Fisher's exact test, and the Cochran-Mantel-Haenszel test. No statistical association was found for dehydration (high urine specific gravity) and preterm contractility. However, pregravid weight below standard body weight-for-height was statistically associated with preterm contractions (P less than .001), as was low weight gain at 30 weeks' gestation (P = .04). There was an association between preterm contractions and both ketonuria (P less than .0001) and the absence of edema (P = .02). Inexpensive clinical measurements of nutritional status may help to identify women at risk for preterm uterine contractility.

Adolescent↗
PubMed1986

Type A behavior, family history of hypertension, and cardiovascular responsivity among black women.

The purpose of this study was to determine the effects of Type A behavior and family history of hypertension on cardiovascular reactivity to mental stress in a group of employed black women. Measures of heart rate and of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken at rest, during a mental arithmetic task, and during the Type A Structured Interview (SI). Results indicated that the Type A behavior pattern was associated with SBP and DBP hyperresponsivity during the SI but not during mental arithmetic. Additionally, certain speech components of the Type A pattern, as well as features of the potential-for-hostility component, were also related to cardiovascular responses during the SI. Family history of hypertension did not influence the cardiovascular parameters either alone or in combination with Type A behavior. The results suggest that many of the cardiovascular response characteristics of the Type A pattern that have been observed in predominantly white samples also hold true for blacks. Replication of these findings with other subgroups of blacks, such as young females and middle-aged males, will help document the generality of these findings within the black population.

Adult↗
PubMed1984

Immunohistochemical localization of neuron-specific enolase in gastroenteropancreatic neuroendocrine tumors. Correlation with tissue and serum levels of neuron-specific enolase.

Neuron-specific enolase (NSE) was studied by immunohistochemistry and radioimmunoassay in ten gastroenteropancreatic (GEP) neuroendocrine tumors. Tissue and serum levels of NSE from the same patients were also analyzed. In all cases, NSE was localized by immunohistochemistry as diffuse cytoplasmic staining to neuroendocrine cells. Tissue levels of NSE were elevated in eight of ten cases while the serum level of NSE was elevated only in one patient with a metastatic gastrinoma to the liver. Examination of the distribution of NSE in a wide range of tumors (n = 55) showed that it is relatively specific for neurons and neuroendocrine tumors. Eight of ten tumors analyzed immunohistochemically for nine polypeptide hormones contained more than one hormone. Two of ten tumors with only one hormone were positive for NSE. The clinical syndrome in all cases was related to only one hormone. These results indicate that the immunohistochemical demonstration of NSE is a good general marker for the neuroendocrine system. While tissue levels of NSE in GEP neuroendocrine tumors are generally elevated, the serum levels of NSE may only be markedly elevated with extensive metastatic disease.

Adenoma↗
PubMed1984

Effect of pethidine, fentanyl and morphine on post-operative shivering in man.

One hundred consecutive patients who shivered following general or regional anesthesia and a surgical procedure were randomly treated with 25 mg pethidine, 2.5 mg morphine, 25 micrograms fentanyl or sodium chloride 0.9%, given in equal intravenous volumes over a 15-min period. The effects were evaluated every 5 min after the first injection. There was a spontaneous, time-related disappearance of shivering in the sodium chloride-treated patients. In the pethidine-treated group, shivering disappeared more than twice as fast as in the control group. The difference was highly significant at 15 and 20 min (P less than 0.001) and was unrelated to weight, body temperature or duration of anesthesia. Women responded sooner than men, reaching significance at 10 min (P less than 0.05), while men did so only at 20 min. Morphine or fentanyl had no effect. Nausea and vomiting were minimal and of equal incidence in narcotic- and placebo-treated patients.

Adult↗
PubMed1983

Comparison of flupirtine maleate and dihydrocodeine in patients following surgery.

Flupirtine maleate 100 mg was compared with dihydrocodeine 60 mg when given by mouth to 50 women on the first 3 days following abdominal hysterectomy in a double-blind parallel-group trial. The analgesia produced was similar for both preparations, and the consumption of active drug was the same in both groups. The only significant differences in side-effects were an increased frequency of depression in patients receiving flupirtine and of sleepiness in those receiving dihydrocodeine.

Adult↗
PubMed1982

Prolactin and growth hormone receptors.

The two hormones prolactin and growth hormone exhibit considerable structural homology as well as exerting similar biological effects, especially the primate hormones. One effect of prolactin that deserves greater attention is its action on the immune system including the stimulation of growth of experimental lymphomas, both in vivo and in vitro. One cultured lymphoma cell line has proved to be a very useful model system in which to examine prolactin receptor synthesis and turnover as well as post-receptor mechanisms of action. Prolactin and growth hormone receptors from rabbit mammary gland and liver respectively have been partially purified and characterized. Polyclonal antibodies to prolactin and growth hormone receptors have been generated. The antibodies have been shown to cross-react with prolactin or growth hormone receptors from a number of species, indicating structural homology among receptors as well as hormones. The polyclonal antisera inhibit the action of prolactin in vivo as well as in vitro. In addition, several of the same antisera also mimic the action of prolactin. As yet the presence of autoantibodies to prolactin or growth hormone receptors in human serum samples has not been recognized.

Animals↗
PubMed1982

Tricyclic-antidepressant-induced delirium and plasma drug concentration.

Fourteen patients receiving routine doses of amitriptyline developed plasma drug concentrations above 300 ng/ml. Of the 7 patients with plasma levels above 450 ng/ml, 6 developed a drug-induced delirium as opposed to none of the 7 with levels below 450 ng/ml. Thus, this adverse effect could be avoided by monitoring levels and reducing dosage when appropriate.

Adult↗
PubMed1982

Arterial vasa vasorum: a quantitative study in the rat.

This study was designed to quantitate the vasa vasorum of common iliac arteries in 20 rats. The number of vasa vasorum per mm2 of arterial wall was extremely variable - from 0 to 124, the mean being 33 . 95 +/- 29 . 86 (S.D.). There was no significant difference in the vasa vasorum vascularity between the right and left common iliac arteries. The mean wall thickness of these arteries was 0 . 085 +/- 0 . 015 (S.D.) mm and 60 +/- 8% (S.D.) of this was made up by the tunica media. Arterial tissue in this study was shown to have approximately 10% of the vascularity of muscle tissue. By relating these data to the 'critical depth' hypothesis, on the nutritional supply of large arteries, it was concluded that the vasa vasorum in the common iliac arteries in rat (major arteries in small animals) probably play an insignificant role in the nutrition of the arterial wall.

Animals↗
PubMed1981

Medical therapies for mood disorders alter the blood-brain barrier.

The effects of amitriptyline, lithium, and electroconvulsive shock on cerebral permeability and blood flow were tested. These three treatments share in common (i) the ability to influence the functional activity of central adrenergic neurons by way of effects on the release, reuptake, or metabolism of norepinephrine and (ii) therapeutic efficacy in mood disturbances. Under control conditions, cerebral permeability increases linealy with increasing arterial partial pressure of carbon dioxide and hence cerebral blood flow. All three treatments altered this relationship in a manner consistent with their adrenergic effects. Amitriptyline potentiated this increase in cerebral permeability whereas lithium and electroconvulsive shock blunted this phenomenon. These results support the hypothesis that one function of central adrenergic neurons is regulation of the blood-brain barrier and raise the possibility that a related effect may underlie the clinical usefulness of such treatment.

Amitriptyline↗
PubMed1981

Nutritional support in an inpatient rehabilitation unit.

Twenty-four patients with protein-calorie malnutrition were treated with intensive dietary support to improve nutritional status. Sixteen patients were able to ingest a mean of 1,945kcal and 77gm protein per 24 hours. Eight patients were unable to consume sufficient protein (11 gm) and kcal (311 gm) per 24 hours; these patients were treated with enteral tube feeding. Patients supported on tube feeding increased serum albumin levels by 0.5gm/100ml and were eventually able to consume 2,170kcal and 87gm of protein per 24-hour period after tube feeding was discontinued. Treatment of patients with protein-calorie malnutrition may require a multiple-modality nutritional support system in a rehabilitation unit.

Humans↗
PubMed1981

Plasma high density lipoprotein cholesterol in streptozotocin diabetic and non-diabetic mice after prolonged administration of glibenclamide, chlorpropamide and metformin.

A possible influence of oral hypoglycaemic drugs on plasma high density lipoprotein cholesterol (HDL-C) concentrations was examined in streptozotocin diabetic and non-diabetic mice. Treatment of streptozotocin diabetic mice with glibenclamide (0.4 mg/kg/day), chlorpropamide (10 mg/kg/day) or metformin (60 mg/kg/day) for 28 weeks did not significantly alter plasma total cholesterol (TC) or HDL-C in streptozotocin diabetic mice. Plasma TC and HDL-C were not related to the prevailing plasma glucose concentration. Non-diabetic mice treated with glibenclamide or metformin for 46 weeks showed no changes in TC or HDL-C. However, chlorpropamide increased TC and HDL-C, and lowered the TC : HDL-C molar ration after 46 weeks in non-diabetic mice. The effect of chlorpropamide was associated with an excessive gain in weight.

Animals↗