A sleep problems information leaflet.
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Biomedical subjects
Publications and source records attributed to S Anderson.
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DNA sequences encoding ribulose 1,5-bisphosphate carboxylase small subunit precursor from Pisum sativum L. have been transcribed from plasmids containing the SP6 promoter, and translated in a wheat germ cell-free system. The small subunit precursor polypeptide, its N-terminal leader sequence (transit peptide) and the mature small subunit have each been synthesized independently from three different plasmid constructs. The precursor polypeptide is imported into isolated pea chloroplasts and processed to the mature small subunit by a stromal proteinase. The mature polypeptide is neither imported, nor subject to proteolysis by stromal extracts. The transit peptide alone is very rapidly degraded by a stromal proteinase activity which can be inhibited by EDTA or 1,10-phenanthroline. The use of these gene constructs helps to establish the crucial role of the transit peptide in protein import into the chloroplast.
A gene for bovine pancreatic trypsin inhibitor (BPTI) was fused to the coding sequence for the Escherichia coli alkaline phosphatase signal peptide and expressed in E. coli under the control of the alkaline phosphatase promoter. When induced in phosphate-depleted medium such cells produced a trypsin inhibitor that was indistinguishable from native, properly folded BPTI. In particular, the BPTI produced by E. coli had three disulfide bonds that appeared to be identical to those found in native BPTI, as assayed by sensitivity to iodoacetate, dithiothreitol, and urea. This expression/secretion system will make possible the production of variant BPTI molecules, thus allowing the perturbing effects of amino acid substitutions on BPTI folding, structure, and function to be assessed.
The nucleotide sequences of two approx. 4 kilobase pair segments of the bovine genome are presented. One segment contains a coding region for bovine pancreatic trypsin inhibitor (BPTI) and the other segment contains a coding region for a BPTI homologue. The two 4 kilobase pair sequences are strikingly similar over approx. 3.4 kilobase pairs of their sequence, including putative intron sequences, suggesting that they have evolved from a gene duplication event.
The combination treatment of mitomycin C (M), vincristine (V), and cisplatin (P) (MVP) in 63 patients with advanced non-small cell lung cancer (NSCLC) were evaluated for their potential synergistic cytotoxicity. The overall response rate was 43% (27/63); in the 54 eligible and evaluable patients, the response rate was 50% (27/54). Responses were observed in all cell types and disease sites. Cell type; performance status of 0, 1, or 2; sex; and age younger or older than 60 years did not significantly influence the response rate. However, patients with prior radiation had significantly more treatment failure than those without. The dose-limiting side effects in these 54 patients were myelosuppression (40%), pulmonary fibrosis (9%), peripheral neuropathy (6%), and intractable nausea and vomiting (4%). The degree of leukopenia (P less than 0.01) but not of thrombocytopenia increased significantly in patients who had received prior radiotherapy. One patient died of marked thrombocytopenia and one of fulminant hepatitis. Patients who responded lived significantly longer than those who did not (P less than 0.004). A majority of the responders (82%) also achieved symptomatic palliation. With appropriate dose modification and supportive care, MVP was tolerable. Further trials with this regimen or a modified version are worth consideration.
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Rabbit aortic smooth muscle cells were prepared by enzymatic digestion of the aortic smooth muscle layer. The cells were subcultured up to Passage 22 starting from a cryogenically preserved stock (approximately 10(10) cells, Passage 8) and characterized morphologically and for 45Ca++ uptake. Microscopically the cells demonstrated the characteristics of vascular smooth muscle cells. 45Ca++ uptake by the cells plated on tissue culture flasks (25 cm2) was determined at 25 degrees C in physiological salt solution (PSS) containing 45Ca++ in low (5 mM) or high (50 mM) KCl concentrations. At the end of the incubation period (0 to 30 min), PSS was aspirated and the cells quickly washed, digested with 0.5 N NaOH, and counted for 45Ca++. High K+ increased the 45Ca++ uptake by 100% or more compared to the low K+ uptake of 45Ca++. This K+-induced 45Ca++ uptake was eliminated in osmotically shocked cells, and inhibited by nifedipine, verapamil, and diltiazem, in a dose-dependent manner. The extent of 45Ca++ uptake and the inhibitory activity of nifedipine were retained up to Passage 22. It is concluded that the developed methodology for scaled-up cultures of rabbit aortic smooth muscle cells provides morphologically intact and biochemically functioning cells suitable for calcium channel studies.
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The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).
The biologic price of aging includes progressive deterioration of renal function and structure. After the age of 30, glomerular filtration and renal blood flow rates decline in a linear fashion, so that values in octagenarians are only half to two thirds those measured in young adults. Renal mass similarly declines, and the incidence of sclerotic glomeruli increases with advancing age. Accordingly, the aging kidney is at high risk of eventual failure when functioning nephron number is further reduced by acquired renal disease. Recent evidence suggests that limitation of dietary protein intake delays the development of age- and disease-related glomerular sclerosis in experimental animals, and that dietary protein restriction may postpone end-stage renal disease in patients with progressive renal insufficiency.
Factors related to the risk of developing clear cell adenocarcinoma in diethylstilbestrol-exposed women were investigated in 156 patients in the United States with clear cell adenocarcinoma and documented diethylstilbestrol exposure (Registry cases) and 1848 diethylstilbestrol-exposed women of similar age without cancer (National Cooperative Diethylstilbestrol Adenosis Project). Diethylstilbestrol dosage patterns, the use of other hormones, mother's age and pregnancy history, and daughter's birth month, birth weight, and age at menarche were compared. The relative risk was higher for those whose mothers began diethylstilbestrol before the twelfth week of pregnancy and for those who were born in the fall (winter conception). Maternal history of at least one prior spontaneous abortion elevated the risk. Supportive evidence for the difference in birth month distribution was also found by a comparison with United States vital statistics. Each factor was confirmed to be significant in a multivariate logistic model that examined all of them with region and year of birth adjusted.
A family is presented in which 7 members over 3 generations were affected by cardioskeletal myopathy. A vacuolar myopathy with excessive free and intralysosomal glycogen storage in skeletal and cardiac striated muscle was identified in biopsy studies. Post-mortem studies in several patients revealed changes of a congestive cardiomyopathy with myocardial fibrosis. Acid maltase, phosphorylase, debrancher and lysosomal enzyme screens, and glycolytic enzyme levels in skeletal muscle, were normal in 1 case. This is the third report of non-acid maltase deficient lysosomal glycogen storage disease and adds to previous reports with the presentation of detailed family studies, examined of ante- and post-mortem cardiac histology and reports of detailed glycolytic and lysosomal enzyme analysis. This syndrome is unusual among glycogenoses in having a dominant inheritance pattern.
A new device has been developed to estimate continuously and noninvasively cardiac output from the thoracic electrical bioimpedance (CObi). CObi was compared to cardiac output by thermodilution (COtd) in five anesthetized dogs. Blood pressure, blood volume, and blood flow were manipulated by hemorrhage and infusions of sodium nitroprusside and phenylephrine. These data were used to determine the correlation between CObi and COtd under conditions of hypotensive normal flow and normotensive low flow, as well as during hemorrhagic shock and resuscitation. The CObi device was calibrated in vivo to COtd for each dog at the beginning of each experiment. CObi had a significant positive correlation with COtd throughout the experiments (r = 0.84, slope = 0.91, intercept = 0.55, p less than 0.01), and CObi predicted COtd with a standard error of the estimate of 0.81 L/min. Neither heart rate nor mean arterial pressure was significantly correlated with COtd or CObi. During severe hemorrhagic shock, CObi could not determine cardiac output in two of the dogs when COtd averaged 1.7 L/min. These data indicate that CObi is a blood-flow related variable that can be monitored continuously.
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The kidney maintains constancy of body fluid volume by regulating urinary sodium (Na) excretion. In chronic renal failure, the reduction in glomerular filtration rate (GFR) is accompanied by an increase in Na excretion per nephron if dietary Na intake is not changed. Reduction in Na intake in proportion to reduced GFR obviates this adaptive increase in tubule Na excretion. To examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the enhanced Na excretion per nephron in chronic renal failure, we studied rats subjected to 5/6 nephrectomy or sham operation on low, normal, and high Na intakes. Urinary Na excretion increased with increasing dietary Na in all groups, and Na excretion per nephron was increased in 5/6 nephrectomized rats as compared with sham-operated rats on the higher Na intakes. Plasma ANP levels were unaffected by dietary Na manipulations in sham-operated rats, but rose progressively in 5/6 nephrectomized rats with increasing Na intake. Despite extensive nephron reduction, however, plasma ANP levels failed to rise in uremic rats on low Na diets and in this group Na excretion per nephron also failed to rise. We conclude that enhanced ANP secretion may play an important role in promoting the adaptive increase in Na excretion per nephron in chronic renal failure. Restriction of dietary Na in the setting of reduced GFR obviates the stimulation of ANP secretion as well as the adaptive increase in Na excretion rate per nephron.
Two groups of adult male Munich-Wistar rats and a third group of nondiabetic age-matched and weight-matched normal control rats underwent micropuncture study 1 mo, and morphologic studies 14 mo, after induction of streptozotocin diabetes or sham treatment. All animals were fed standard rat chow. Diabetic rats received daily ultralente insulin to maintain stable moderate hyperglycemia (approximately 350 mg/dl). In addition, one group of diabetic rats was treated with the angiotensin I converting enzyme inhibitor, enalapril, 15 mg/liter of drinking water. Average kidney weight, whole kidney and single-nephron glomerular filtration rate, and glomerular plasma flow rate were elevated to similar values in both groups of diabetic rats, relative to normal control rats. Non-enalapril-treated diabetic rats exhibited significant elevations in mean glomerular capillary hydraulic pressure and transcapillary hydraulic pressure gradient, compared with the other groups studied, and only this group eventually developed marked and progressive albuminuria. Likewise, histological examination of the kidneys at 14 mo disclosed a high incidence of glomerular structural abnormalities only in non-enalapril-treated diabetic rats. These findings indicate that prevention of glomerular capillary hypertension in rats with diabetes mellitus effectively protects against the subsequent development of glomerular structural injury and proteinuria. This protection is afforded despite pronounced hyperglycemia and elevated levels of glucosylated hemoglobin, further supporting our view that hemodynamic rather than metabolic factors predominate in the pathogenesis of diabetic glomerulopathy.
Micropuncture and morphologic studies were performed in six groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney. Groups 1 and 4 received no specific therapy. Groups 2 and 5 were treated with the angiotensin I-converting enzyme inhibitor, enalapril, 50 mg/liter, in the drinking water. Groups 3 and 6 were treated with reserpine (5 mg/liter), hydralazine (80 mg/liter), and hydrochlorothiazide (25 mg/liter). All rats were fed standard chow. Groups 1-3 underwent micropuncture study 4 wk after renal ablation. Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure gradient (delta P) and glomerular plasma flow rate (QA). In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained delta P at near-normal levels without significant reduction in SNGFR and QA. In contrast, triple drug therapy normalized systemic hypertension, but failed to lower delta P in group 3 rats. Groups 4-6 were followed for 12 wk after renal ablation. Untreated group 4 rats demonstrated continuous systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and frequent areas of segmental sclerosis. In group 5 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 12-wk period and dramatically limited the development of proteinuria and glomerular lesions. Despite equivalent systemic blood pressure control in group 6 rats, failure of triple drug therapy to control glomerular hypertension was associated with progressive proteinuria and glomerular lesions comparable to those seen in untreated group 4 rats. Thus, unless glomerular capillary hypertension is corrected, control of systemic blood pressure is insufficient to prevent progressive renal injury in rats with reduced renal mass.