Lack of association between type of hepatitis C virus, serum load and severity of liver disease

The NOD mouse is known as a spontaneous model of insulin-dependent diabetes mellitus. Fetuses in this strain present anomalies of the viscera, and the incidence increases in fetuses from dams with clinically manifested diabetes. To examine the role of maternal diabetes and the genetical influence in inducing heterotaxy, NOD dams were mated with males of the ICR strain (the original strain of the NOD) and with C57BL/6J sires (not genetically related to the NOD). The frequency of visceroatrial heterotaxy in fetuses from diabetic dams varied with the fetal genotype, being 65% (33/51) in NODxNOD (dam X sire, respectively), 24% (12/50) in NODxICR, and 7% (4/57) in NODxC57BL/6J. The cases with heterotaxy showed a tendency toward right isomerism of the viscera and had severe cardiac defects, such as endocardial cushion defect and double-outlet right ventricle or transposition of the great arteries. The fetal body weight from diabetic dams in each mating was lower than that from non-diabetic dams (P < 0.05), suggesting that maternal diabetes, rather than abnormal situs, is the main determinant for decreased fetal growth. These findings demonstrate that the liability to heterotaxy induced by maternal diabetes is influenced by the fetal genotype.     

Effect of different experimental parameters on the potentiometric evaluation of blood electrolytes using K+ as a test cation

Potentiometric evaluation of ionic concentrations in physiological media has been reported to be significantly affected by the albumin containing matrix. Previous studies have attempted to clarify the origin of different patterns of variation of E versus albumin concentration at a constant 0.01 mol dm-3 KCl, depending on the experimental methodologies. This paper reports on measurements of K+ in albumin (BSA) containing KCl solutions, which have been pursued following different methodologies concerning the sequence of measurements, i.e., starting either from the most concentrated solution (100 g dm-3) (A) or from the most dilute solution (20 g dm-3) (B), and solution preparation, (a) dilution of an initial 100 g dm-3 albumin solution by successive addition of 0.01 mol dm-3 KCl, (b) concentration of an initial 20 g dm-3 albumin solution by addition of solid substance, (c) independent preparation of each albumin solution (20, 40, 60, 80 and 100 g dm-3) or (d) preparation of each albumin solution from direct dilution of a 100 g dm-3 stock solution with 0.01 mol dm-3 KCl. Convenient calculations were made and showed a significant contribution of albumin to the liquid-liquid junction potential. The variation of potential with albumin concentration is smaller for hypertonic than for isotonic bridge solutions, both for the dilution series (A,a and A,d) and for the concentration series (B,c and B,d). When the method for increasing the concentration is performed by addition of a solid substance to an initially diluted albumin (B,b), the slope of the E versus albumin concentration plot is larger for hypertonic than for isotonic reference electrolytes. This latter finding is in agreement with Payne's results when ultrafiltration was used to concentrate a protein solution. These observations are a clear indication that the method of preparation of concentrated protein solutions may significantly affect the results.     

Periodic health examinations. Why? What? When? How?

Pulmonary blastoma is now accepted as a distinctive neoplasm. It remains rare, and only 28 cases have been reliably recorded. A further two cases are now reported, and the previous literature is reviewed. There are no specific clinical or radiological features of pulmonary blastoma. The presentation can be that of any other pulmonary tumour although a peripheral situation is usual and a large size is often attained before detection. Pulmonary blastoma is a mixed tumour with malignant epithelial and connective tissue components with a distinctive resemblance to fetal lung. The treatment of choice is surgical excision but the overall prognosis is poor. It is doubtful whether the tumour has a true blastomatous origin.     

Posttraumatic Budd-Chiari syndrome treated with thrombolytic therapy and angioplasty

In this study we compared the frequency and pattern of p53 mutations in 34 bladder tumors from people with high-level occupational exposure to arylamines to those in 30 bladder tumors from people without such exposure. No differences were observed for p53 mutations between the two groups. The frequency of mutation was similar at 47% for arylamine-exposed individuals and 53% for unexposed individuals and showed a similar pattern of mutation, with GC to AT transitions accounting for the majority of the mutations in both groups. This finding suggests that arylamine exposure does not leave a mutational "footprint" in the p53 gene. However, compared to other tumors, bladder tumors from both exposed and unexposed individuals had a high frequency of multiple mutations and it is interesting that these mutations were highly concordant. We suggest that one explanation of this pattern of mutations could be from decreased DNA repair fidelity within tumor cells. The frequency of mutation in p53 is closely linked to tumor grade and stage and so may be a late event in the development of bladder tumors.     

pH in human tumor xenografts and transplanted rat tumors: effect of insulin, inorganic phosphate, and m-iodobenzylguanidine

Various strategies to improve the therapeutic index of anticancer agents aim at inducing, by stimulation of aerobic glycolysis, temporary pH differences between malignant and normal tissues which can be exploited to activate cytotoxic agents selectively in tumors. We have investigated whether the pH reduction induced by glucose, the "drug" commonly used to increase lactic acid production in malignant tissues, can be augmented by pharmacological manipulation of tumor cell glycolysis. At normal plasma glucose concentration (6 +/- 1 mM), inorganic phosphate, a modifier of hexokinase and phosphofructokinase activity, had no effect on pH in two transplanted rat tumors and a human tumor xenograft line (average pH, 6.80; range, 6.65-6.95). When plasma glucose concentration was raised to 30 +/- 3 mM by i.v. infusion of glucose, inorganic phosphate reduced the pH in those tumors which exhibited only a moderate pH response to glucose per se (mean pH, 6.60) to an average value of 6.20 (range, 6.05-6.35). In the same setting, insulin, continuously infused at dose rates up to 600 milliunits/kg body weight/min, did not result in acidification of tumor tissue exceeding that induced by glucose alone. However, the H+ ion activity in both transplanted rat tumors and human tumor xenografts was increased by m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. For example, at normoglycemia, MIBG reduced the mean pH in a human mesothelioma xenograft from 6.90 to 6.70. This pH value was further reduced to 6.20 by simultaneous low-dose i.v. glucose infusion (plasma glucose concentration, 14 +/- 3 mM). The acidosis induced by inorganic phosphate and MIBG was tumor specific. Normal tissues of tumor-bearing hosts were only marginally sensitive to hyperphosphatemia or MIBG administration. These results indicate that the known stimulatory effect of exogenous glucose on lactic acid production in malignant tumors in vivo can be further accentuated or, as in the case of MIBG, partially replaced by pharmacological manipulation of aerobic glycolysis using clinically established drugs.     

Dependence of rates of lipolysis, esterification, and free fatty acid release in isolated fat cells on age, cell size, and nutritional state

Rates of lipolysis, esterification, and free fatty acid release were estimated in isolated epididymal fat cells prepared from rats fed either ad lib. or with a restricted caloric intake. Basal and epinephrine- or theophylline-stimulated rates of lipolysis correlated positively with cell size in the ad lib.-fed group only. Rates of esterification, both basal and epinephrine-stimulated, correlated positively with cell size in the ad lib.-fed group but negatively in the caloric-restricted group. These findings indicate that nutritional factors can modify any possible influence of adipose cell size on lipolysis and esterification. On the other hand, in both groups of rats, epinephrine- and theophylline-stimulated rates of lipolysis correlated positively with the basal rates of lipolysis. Also, rates of esterification in the presence of epinephrine correlated positively with the basal rates of esterification, suggesting that stimulated rates of lipolysis and esterification are at least partly determined by the basal rates regardless of nutritional status. The activity of glycerokinase measured in homogenates of isolated fat cells, if applicable to intact fat cells, was sufficient to cause considerable underestimations of the basal rates of lipolysis (using glycerol production as an index). When lipolysis was stimulated, the potential errors of estimating lipolysis by glycerol production alone were negligible.