Activity of the plasma membrane H(+)-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid

The weak acid sorbic acid transiently inhibited the growth of Saccharomyces cerevisiae in media at low pH. During a lag period, the length of which depended on the severity of this weak-acid stress, yeast cells appeared to adapt to this stress, eventually recovering and growing normally. This adaptation to weak-acid stress was not due to metabolism and removal of the sorbic acid. A pma1-205 mutant, with about half the normal membrane H+-ATPase activity, was shown to be more sensitive to sorbic acid than its parent. Sorbic acid appeared to stimulate plasma membrane H+-ATPase activity in both PMA1 and pma1-205. Consistent with this, cellular ATP levels showed drastic reductions, the extent of which depended on the severity of weak-acid stress. The weak acid did not appear to affect the synthesis of ATP because CO2 production and O2 consumption were not affected significantly in PMA1 and pma1-205 cells. However, a glycolytic mutant, with about one-third the normal pyruvate kinase and phosphofructokinase activity and hence a reduced capacity to generate ATP, was more sensitive to sorbic acid than its isogenic parent. These data are consistent with the idea that adaptation by yeast cells to sorbic acid is dependent on (i) the restoration of internal pH via the export of protons by the membrane H+-ATPase in an energy-demanding process and (ii) the generation of sufficient ATP to drive this process and still allow growth.     

Imaging evaluation of artificial nipples during bottle feeding

OBJECTIVE: To report a case of probable famotidine-induced mixed hepatocellular jaundice. CASE SUMMARY: A 55-year-old man presented with a one-month history of mid-epigastric pain. Initial physical examination and laboratory studies, including liver enzyme concentration tests, were unrevealing. A diagnosis of gastritis was made and ranitidine was prescribed. Following one week of therapy, the patient's symptoms had not improved and therapy was changed to famotidine and sucralfate. Approximately one week later the patient presented with jaundice. Liver enzyme concentrations were elevated and the patient was hospitalized for further evaluation. Five days following discontinuation of famotidine, liver enzyme concentrations were normal and jaundice had resolved. Further tests did not reveal any pathologic etiology. DISCUSSION: Hepatic changes have occurred in patients receiving histamine2-antagonists; ranitidine and cimetidine have been cited most frequently. In general, the elevations are mild, transient, and return to baseline with continued therapy. This is one of the first case reports of probable famotidine-induced mixed hepatocellular jaundice. CONCLUSIONS: There was a temporal relationship between the patient's signs and symptoms and initiation of famotidine. No identifiable factors contributed to the elevated liver enzyme concentrations and jaundice.     

Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Reduced speed of sound in tibial bone of haemodialysed patients: association with serum PTH level

BACKGROUND: In end-stage renal disease, average bone mineral density has been reported to be normal or only modestly reduced, more so in the cortical bone. The purpose of the present study was to explore the potential use of quantitative ultrasound, a method reflecting both quantitative and qualitative properties of bone, in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17-81 years, time on dialysis 0-18 years). The speed of sound waves (tSOS; m/s) propagating along the cortical bone has been determined at the tibial shaft. tSOS results were expressed as Z scores, i.e. units of standard deviations from age- and sex-matched normal mean values, and correlated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged -2. 0 (range -6.8 to 0.6; P<0.001) and was negative in 93% of the patients. Significant inverse correlations were found between SOS Z score and both time on dialysis (r=-0.52; P<0.0001) and serum PTH (r=-0.39; P=0.0002). Markedly reduced SOS Z score, below -2, was found in 80% of the patients whose PTH levels exceeded 34 pmol/l (five times the upper normal limit), compared with 43% of the patients whose PTH levels were below 34 pmol/l(P=0.04). Compared to patients without bone pain (n=51), subjects with bone pain (n=20) had somewhat lower SOS Z scores -2.5+/-2.0 versus -1.8+/-1.4; P=0. 08), but this could be accounted for by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysed patients and is related to time on dialysis and serum PTH level. The clinical value of this novel method needs further exploration.     

Phenotypic analysis of antigen-specific T lymphocytes

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.     

Phytohemagglutinin-induced gut hyperplasia and the growth of a mouse lymphosarcoma tumor

OBJECTIVE: To identify possible causes for the increased cardiovascular morbidity and mortality seen in patients with primary hyperparathyroidism. DESIGN: Prospective, blind study. SETTING: University hospital, Sweden. SUBJECTS: 44 Patients with primary hyperparathyroidism and 23 (sex and age matched) control patients with atoxic nodular goitres. INTERVENTIONS: Exploration of the neck with removal of pathological parathyroid glands or thyroid resection. Echocardiography before, and one year after, the operation. MAIN OUTCOME MEASURES: Blood pressure and echocardiographic findings. RESULTS: Hyperparathyroid patients had higher blood pressure and greater left atrial diameter than control patients preoperatively. They also had a significantly lower E:A ratio (mitral flow velocity pattern) than the controls (p = 0.02) indicating a disturbance in early diastolic filling of the left ventricle. The E:A ratio correlated negatively with the systolic blood pressure. 19 of the hyperparathyroid patients (43%) had cardiac calcifications as did 14 (61%) of the controls. Most of calcifications were located in the aortic and mitral valves; only a few patients had calcifications in the myocardium. No significant changes had occurred one year after parathyroidectomy, except for a reduction in systolic blood pressure, in the hyperparathyroid patients. CONCLUSION: Echocardiographic investigation of patients with primary hyperparathyroidism shows early signs of left ventricular dysfunction that may be of clinical importance.     

Corrosion of implantable materials and aging of bone

This article is a review of how metallic implant corrosion byproducts affect the long-term survival of the dental implant bone bed. Cell structure, bone loss, metal release and corrosion mechanisms are explained in relation to how they influence the metabolic factors that control bone remodeling.     

Endothelium-dependent vasodilatation is impaired in peritoneal dialysis patients

BACKGROUND: Peritoneal dialysis (PD) patients have a high risk of cardiovascular mortality, which is not completely explained by conventional risk factors. Other factors related to chronic renal failure and/or dialysis treatment might lead to endothelial dysfunction, which is associated with an adverse cardiovascular outcome. One such factor is hyperhomocysteinaemia, which has a high prevalence in PD patients. METHODS: A vessel wall movement detector system was used to investigate endothelium-dependent, flow-mediated, and endothelium-independent, glyceryl trinitrate-induced, vasodilatation of the brachial artery in 29 PD patients and 29 control subjects. RESULTS: Endothelium-dependent vasodilatation was markedly reduced in the PD group: 5.7 +/- 1.0% vs 10.4 +/- 1.3% in the control group (P = 0.004). Endothelium-independent vasodilatation was not impaired. Plasma total homocysteine was elevated in the PD patients (45.2 +/- 6.2 micromol/l), but was not related to endothelium-dependent vasodilatation. CONCLUSION: Chronic peritoneal dialysis patients have impaired endothelium-dependent vasodilatation, which may reflect an increased susceptibility for the development of atherosclerosis and thrombosis.