Characteristic elevation of soluble TNF receptor II : I ratio in macrophage activation syndrome with systemic juvenile idiopathic arthritis.

To investigate the clinical significance of soluble tumour necrosis factor receptor (sTNF-R) II/I ratio as an indicator of the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA), we measured the serum sTNF-RI and II levels in 117 patients with s-JIA, including 29 patients with MAS, 15 with Epstein-Barr virus-induced haemophagocytic lymphohistiocytosis (EBV-HLH), 15 with Kawasaki disease (KD) and 28 healthy controls (HCs). We determined their correlation with measurements of disease activity and severity. Furthermore, we measured serum interleukin (IL)-18 levels in patients with EBV-HLH and compared these in levels in patients with MAS. The sTNF-RII/I ratio was elevated significantly in MAS and EBV-HLH patients compared with those in the acute phase of s-JIA and KD patients, whereas there were no significant differences between HCs and those in the acute phase of s-JIA. The sTNF-RII/I ratio increased profoundly as MAS developed and correlated positively with disease activity. Serum IL-18 levels were elevated significantly in MAS patients compared with EBV-HLH patients. The monitoring of serum IL-18 and sTNF-RII/I might be useful for the diagnosis of MAS and the differentiation between MAS and EBV-HLH.

Pioglitazone attenuates fatty acid-induced oxidative stress and apoptosis in pancreatic beta-cells.

AIMS: Thiazolidinediones (TZDs), ligands for peroxisome proliferator-activated receptor gamma, are antidiabetic agents that improve hyperglycemia by decreasing insulin resistance in obese diabetic animal models and patients with type 2 diabetes. We have studied whether pioglitazone, a TZD, can exert a direct effect against pancreatic beta-cell lipoapoptosis. METHODS: MIN6 cells were cultured in medium containing either 5.6 (low glucose) or 25 mM glucose (high glucose) in the presence or absence of 0.5 mM palmitate for 48 h. We examined the effect of 10 microM pioglitazone on MIN6 cells on glucose-stimulated insulin secretion, cellular ATP, uncoupling protein-2 (UCP-2) mRNA expression, intracellular triglyceride content, reactive oxygen species production, the number of apoptotic cells and nuclear factor-kappaB (NF-kappaB) activity. RESULTS: Pioglitazone recovered partly impaired glucose-stimulated insulin secretion and cellular ATP in MIN6 cell exposed to high glucose with 0.5 mM palmitate. Pioglitazone suppressed intracellular triglyceride accumulation in cells exposed to high glucose with 0.5 mM palmitate. Palmitate-induced upregulation of UCP-2 mRNA levels was suppressed by pioglitazone in a dose-dependent manner. Pioglitazone decreased palmitate-induced reactive oxygen species production in MIN6 cells by 24% and in mouse islet cells by 53%. Pioglitazone also decreased palmitate-induced NF-kappaB activity by 40% and protected beta-cells from palmitate-induced apoptosis by 22% in MIN6 cell. CONCLUSIONS: Pioglitazone attenuated fatty acid-induced oxidative stress and apoptosis in pancreatic beta-cells. TZDs might be used as a mean for maintaining beta-cell survival and preserving capacity of insulin secretion in patients with diabetes mellitus.

Localization and functional role of synaptotagmin III in insulin secretory vesicles in pancreatic beta-cells.

Pancreatic beta-cells secrete insulin by Ca2+-triggered exocytosis of insulin-containing large dense-core vesicles. Synaptotagmin is a Ca2+/phospholipid-binding protein and is a good candidate for the Ca2+ sensor for exocytosis of synaptic vesicles in neurons. In the present study, we generated a polyclonal antibody against synaptotagmin III, and found that synaptotagmin III immunoreactivity was present at high levels in insulin-containing pancreatic islet cells and insulin-secreting clonal MIN6 cells. In subcellular fractionations of MIN6 cells, synaptotagmin III was recovered in the vesicular fractions containing both insulin and vesicle-associated membrane protein-2 (VAMP-2), but not in synaptophysin-positive fractions. The secretory vesicles immunoprecipitated by anti-VAMP-2 antibody contained synaptotagmin III and insulin. In addition, treatment of streptolysin-O-permeabilized MIN6 cells with anti-synaptotagmin III antibody significantly inhibited Ca2+-triggered insulin secretion. These results indicate that synaptotagmin III is localized in insulin-containing dense-core vesicles in pancreatic beta-cells, and further strongly suggest that synaptotagmin III is the Ca2+ sensor in the exocytosis of insulin secretory vesicles.

A mathematical model of the volume effect which postulates cell migration from unirradiated tissues.

PURPOSE: In order to simulate the large variation in tolerance doses for very small treatment volumes, we introduce a model which assumes the presence of cells which have migrated from unirradiated tissues. METHODS AND MATERIALS: In order to represent serial architecture, the new model adds a new parameter to the familiar expression for serial architecture. Data derived from the model is fitted to the dose-response data developed by Hopewell et al. (Hopewell, J.W., Morris, A.D. and Dixon-Brown, A. The influence of field size on the late tolerance of the rat spinal cord to single doses of X rays. Br. J. Radiol. 60: 1099-1108, 1987) using white matter necrosis of rat spinal cord. RESULTS: The new model with a cell-migration term more accurately describes the large differences in threshold doses for a very small treatment volume than a model without a cell-migration term. CONCLUSION: Although these results do not prove that cell migration is the mechanism behind the volume effect for very small volume, they do suggest that the probability of normal tissue complication is more accurately predicted by the new model.

Detection of interstitial Ga in GaN

We report the direct detection of interstitial Ga by optical detection of electron paramagnetic resonance (ODEPR) in the photoluminescence of n-type GaN after irradiation in situ at 4.2 K with 2.5 MeV electrons. It is stable upon annealing until room temperature, where it becomes mobile and trapped to form a new defect which is observed to emerge as the interstitial disappears. The time constant of the process at room temperature is approximately 200 min. The emergence of another ODEPR center beginning at approximately 135 K suggests even easier migration of one of the other intrinsic defects in the GaN lattice.

Cloning of a mouse Rabphilin-3A expressed in hormone-secreting cells.

Rab3A, a ras p21-related small GTP-binding protein, is implicated in the exocytosis of neurotransmitters. Recently, Rabphilin-3A, a putative target protein for Rab3A, was identified and its cDNA has been cloned from bovine brain. In this study, we isolated a cDNA encoding a mouse Rabphilin-3A homolog from the insulin-secreting cell line, MIN6. Mouse Rabphilin-3A is a protein of 681 amino acids exhibiting overall 88.5% identity with bovine Rabphilin-3A. The amino acid identity between mouse and bovine Rabphilin-3A is highest in their carboxyl-terminal halves (97.8% identity) and amino-termini (93.0% identity), which contain the region of the two internal repeats homologous to the regulatory domain (C2 domain) of protein kinase C and the putative Rab3A-binding region, respectively. RNA blot analysis revealed that Rabphilin-3A mRNA is expressed in endocrine and hormone-secreting clonal cells, including rat adrenal glands, MIN6, the hamster insulin-secreting cell line, HIT-T15, and the rat catecholamine-secreting cell line, PC12, as well as rat brain. These results suggest that Rabphilin-3A might be involved in the exocytosis of secretory vesicles in hormone-secreting cells as well as in neurons.

Mutagenic activities of dictamnine and gamma-fagarine from dictamni radicis cortex (Rutaceae).

A methanol extract of Dictamni Radicis Cortex exhibited a mutagenic effect on Salmonella typhimurium TA100 and TA98 with S9 mix. Two mutagenic compounds in Dictamni Radicis Cortex were isolated on a Sephadex LH 20 column and silica gel column chromatography and by preparative TLC. These were identified as dictamnine and gamma-fagarine by UV, EI-Mass, 1H-NMR. Dictamnine and gamma-fagarine were mutagenic in strain TA100 and TA98 with S9 mix. The dose-response curves were linear in the range 10-40 micrograms. Dictamnine and gamma-fagarine had specific activities (His+/microgram) of about 50-70 revertant colonies in strain TA100, while in strain TA98 there were about 30-50 revertant colonies.

Time-course of mutagenicity due to flavonols in a pickled vegetable.

The mutagenicity of the leafy vegetable, Takana (Brassica juncia var. integrifolia), pickled with salt for various durations was examined. The mutagenicity increased with increasing duration of pickling time, and analysis by HPLC showed that is was caused by mutagenic flavonols. The flavonols contained in the fresh Takana as glycosides were found to be freed by pickling. This was confirmed by acid hydrolysis.

A candidate case for lymphocytic infundibulo-neurohypophysitis mimicking a neurohypophysial tumor.

A 56-year-old Japanese man presented with a 2-month duration of polyuria and polydipsia. The diagnosis of diabetes insipidus was confirmed by water deprivation and vasopressin injection. The secretory function of the adenohypophysis was estimated as normal by a variety of provocative tests. Magnetic resonance imaging (MRI) displayed the loss of the hyperintense signal of the neurohypophysis and a tumor-like lesion confined to the neurohypophysis. The tissue specimen resected at transsphenoidal surgery showed diffuse lymphocytic infiltration. These findings suggest that this is a candidate case for lymphocytic infundibuloneurohypophysitis (LIN) that is not identical to classical lymphocytic hypophysitis. This patient will be followed up to determine whether this case simply represents an early stage of classical hypophysitis or a different clinical entity.

Clinical implications of alpha-fetoprotein in liver cirrhosis: five-year follow-up study.

The level of alpha-fetoprotein (AFP) was estimated by radioimmunoassay or passive hemagglutination method in a series of 159 patients with liver cirrhosis, and the incidence of serum hepatitis B antigen, histopathologic features of the liver, incidence of development of hepatocellular carcinoma (HCC) and mortality in AFP-positive cases were studied. Approximately 40 per cent of the patients had an AFP level higher than 20 ng/per ml, and all the elevations of AFP over 100 ng per ml were transient. In contrast, patients who developed HCC during the course of the disease always exhibited an increasing value of AFP. The seropositivity for AFP was significantly related to the presence of serum hepatitis B surface antigen and also to liver cell dysplasia as well as to thickening of the liver cell plates. As compared with a group of AFP-negative cases, the AFP-positive group showed a higher incidence of development of HCC and poorer prognosis over a five-year follow-up period. The data obtained suggested that increased AFP-production in patients with liver cirrhosis might reflect, largely an abnormal or altered liver cell regeneration, probably associated with hepatitis B virus, and that patients with transiently elevated AFP values might be at greater risk for the development of HCC.

Studies of alpha-napthylisothiocyanate-induced hepatic disturbance.

In order to clarify the mechanism of alpha-naphthylisothiocyanate (ANIT) induced cholestasis in rats, a few hepatic changes seen after administration of ANIT 80 mg/kg body weight were examined in relation to time. To clarify changes in the bile production system and bile flow, the concentrations of bile acid and bicarbonate, as well as of sodium in the bile, were measured after infusion of secretin and taurocholic acid. The canalicular bile flow was estimated by measuring the biliary clearance of erythritol-C14. To assess hepatocellular injury, the levels of cytochrome P-450 in the microsome of hepatocytes and protein synthesis in the liver were estimated. It seems that ANIT is activated in the drug metabolising system through cytochrome P-450 in the liver, and significant changes are produced in both the bile acid metabolism and its transport system. Bile acid-independent bile flow in the canaliculus was inhibited, too. Hence, both the bile ductules and the bile ducts are functionally and histologically disturbed.

[Characteristics of home parenteral nutrition and effectiveness of 3 way valved PICC in regional medical care].

Home medical care is becoming a greater matter of concern along with the increasing population of elderly persons. The various difficulties in home care are also found in regional care, and it could be said that in Japan regional care serves as an "advanced model" for home medical care. Ohya Town is located in the mountains of northern Hyogo Prefecture. It has a population of about 5,000 of which 32% is elderly people. There is no railroad, and it takes around 30 minutes to travel to the central hospital from the area. The three town clinics are in contact with each other and with the central hospital concerning medical information. The characteristics of Home Parenteral Nutrition in this underpopulated district are discussed and reported in reference mainly to cases in which the 3 way valved peripherally inserted central venous catheter (Groshong Catheter) is used, in comparison with HPN cases in the city university hospital.