[Protein immobilization in lipid bilayer membrane films on electrodes and their electron transfer reactions].
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Biomedical subjects
Publications and source records attributed to N Nakashima.
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This report discusses a rare case of giant cell-rich osteosarcoma. The patient, a 19-year-old male, was diagnosed with a metadiaphyseal osteolytic lesion when he consulted a local doctor complaining of motion pain without swelling. Radiography revealed a geographic osteolytic lesion, cortical thinning and ballooning without obvious cortical destruction. However, a fine onion skin-like periosteal reaction was observed on the lateral side of the femur. The transitional none was narrow and endosteal scalloping was also noted. Needle biopsied material clearly showed nuclear atypism of the stromal tumor cells with numerous osteoclast-like giant cells. Using a combination of pathological examination, radiography, computed tomography (CT) and magnetic resonance imaging (MRI), a diagnosis of giant cell-rich osteosarcoma was reached. After chemotherapy, resection and limb salvage surgery with an autogeneous autoclaved bone graft, a vascularized fibular graft were performed, and the patient has shown excellent limb function without local recurrence or distant metastasis during the past 72 months.
In the yeast cell cycle 'start' requires sets of the Cdc10/ SWI family of transcriptional factors which activate the MCB cis elements contained in genes essential for S phase progression. Fission yeast possess two such overlapping systems, Res1-Cdc10 and Res2-Cdc10, both of which act to start the mitotic and meiotic cycles. We have recently isolated rep2+ as a multicopy suppressor of a temperature-sensitive cdc10 mutant which encodes a zinc finger protein. Here we show that the Rep2 zinc finger protein is an essential component of the active Res2-Cdc10 transcriptional regulator complex and likely to play a role in the control of cell cycle 'start'. Our data suggest that Rep2 is a transcriptional activator subunit which interacts with the MCB binding subunit complex formed by Res2 and Cdc10.
Nilaparvata lugens reovirus (NLRV) was found in a colony of the brown planthopper, N. lugens, an important plant virus vector. Unlike with usual phytopathogenic reoviruses, there are no visible symptoms on a rice plant which has been attacked by NLRV-infected planthoppers. Manner of transmission, host range, and multiplication of NLRV in rice plant were studied by enzyme-linked immunosorbent assay or polymerase chain reaction using reverse transcriptase. NLRV was transovumly transmitted to about 15% of nymphs. NLRV could further spread to planthoppers via rice plants through sucking by viruliferous insects. This horizontal transmission was apparently of primary importance for continuous NLRV infection to a colony of N. lugens. By corearing with viruliferous N. lugens on rice seedlings, Laodelphax striatellus acquired NLRV but Sogatella furcifera, Nephotettix cincticeps, and N. malayanus did not during the period studied. NLRV inoculated onto rice plant by viruliferous N. lugens failed to multiply, which accounts for the lack of symptoms on the plant even after an attack by viruliferous planthoppers. These biological properties and our previous data, which revealed a molecular similarity between NLRV and fijiviruses, suggest that NLRV is an ancestral virus of fijiviruses.
We examined IL-6 levels in the cerebrospinal fluid (CSF) of patients clinically diagnosed with Alzheimer-type dementia (ATD) and with vascular dementia (VD) and of age-matched normal subjects. The IL-6 levels in the CSF of ATD, but not VD patients, were significantly decreased. In the early onset ATD patients (disease onset < 65 years), IL-6 levels were reduced to 21% of the control level. The IL-6 levels in the CSF were not associated with the severity of the dementia or the duration of the disease since the identification of the first symptoms.
A case of gonadoblastoma with dysgerminoma in the left ovary and gonadoblastoma with dysgerminoma and yolk sac tumor in the right of a 10-year-old girl is reported. Her karyotype was 46XX, normal female type. A case of a gonadoblastoma without a Y chromosome is very rare. Furthermore, the prognosis for gonadoblastoma accompanied by germ cell tumors other than dysgerminoma was very poor in the past, but the patient remains well 25 months after the first operation.
The authors describe newly designed microclips and their utility in obtaining haemostasis during the surgical resection of cerebral arteriovenous malformations. The microclips are particularly well-suited for controlling bleeding from small fragile vessels often encountered on the periphery of large arteriovenous malformations during the final stages of a surgical procedure. Histological examination of these vessels revealed very thin dilated walls without elastic layers, causing easy rupture. Hence, haemostasis using conventional means, such as bipolar coagulators, can be extremely difficult. We have used microclips on such vessels in 14 patients with arteriovenous malformations and controlled bleeding successfully.
Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) reportedly have antidiabetic and antiobesity effects. The effect of DHEA on glucose uptake in cultured human fibroblasts was examined. Incubation of cells with supraphysiologic concentrations of DHEA (10(-5) mol/L) for > or = 10 hours enhanced 2-deoxyglucose (2-DG) uptake significantly (P < .05). Supraphysiologic concentrations of insulin (10(-7) mol/L) increased the sensitivity of glucose uptake to DHEA. Conversely, the sensitivity of glucose uptake to insulin was increased by incubating cells with 10(-6) mol/L DHEA. Both the abundance of transcripts encoding glucose transporter-1 (Glut-1) and the maximal velocity (Vmax) of 2-DG transport were increased in cultured fibroblasts incubated with DHEA. Cultured fibroblasts expressed a specific binding factor with low affinity for [3H]DHEA (maximal number of binding sites, 18,496 sites per cell; Kd, 298 nmol/L). Other androgen hormones exerted a less-marked effect on glucose uptake; DHEA-S had no effect. These results suggested that DHEA increases Glut-1 mRNA through binding to a specific factor in cultured human fibroblasts and thereby stimulates glucose uptake in these cells.
The rice planthoppers, Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus, harbor intracellular yeast-like symbiotes (YLS) in the fat body. The YLS are obligated endosymbiotes and are transovarially inherited. Nucleotide sequences of the 18S rRNA genes from the YLS were analyzed by direct sequencing. The YLS of the three species of planthoppers were monophyletic and their taxonomic positions were in the class Pyrenomycetes in the subphylum Ascomycotina.
The effects of dehydroepiandrosterone (DHEA) on glucose uptake and on insulin sensitivity were studied in cultured rat myoblasts (L6 cells). Preincubation with supraphysiological doses of DHEA (10(-5) M approximately significantly enhanced (p < 0.05) the cellular uptake of [3H]-2-deoxyglucose. Glucose uptake was significantly increased in cells exposed to 10(-4)M DHEA for 10 hours (p < 0.005), and for 24 hours (p < 0.001), but not for 3 hours. An increase in DHEA sensitivity with an enhanced glucose uptake was observed in cells exposed to 10(-7)M of human insulin. Insulin sensitivity was increased by preincubating the cells with 10(-6)M of DHEA. Other androgens enhanced the effect on glucose uptake to a lesser extent. DHEA sulfate had no effect on L6 cells, suggesting that the effect may be specific for DHEA, not common to androgens, Sulfation of DHEA may negate the effect. In reciprocal plot analysis, the Km value for glucose transport was decreased by preincubation with DHEA (from 0.67 mM without DHEA, 0.56mM with 10(-5)M DHEA, and 0.25mM with 10(-4) M DHEA), although Vmax was unchanged, We conclude that DHEA increases the affinity of glucose transport in the plasma membrane of cultured rat myoblasts, leading to an enhanced glucose uptake and an increase in insulin sensitivity.
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Mutation of the insulin receptor gene can compromise the ability of the receptor to mediate insulin action. A homozygous point mutation that results in the substitution of histidine for arginine 252 in the insulin receptor alpha-subunit has now been identified by polymerase chain reaction and single stranded conformational polymorphism analysis in a 20-yr-old Japanese woman with type A syndrome and severe insulin resistance. The proband's consanguineous parents (diabetic mother and normal father) and her sister (impaired glucose tolerance), each of whom showed an exaggerated insulin response to an oral glucose load, were heterozygous for this mutation. Her brother showed a normal insulin response and lacked the mutation, as did 50 healthy Japanese control subjects. The chronic sc administration of insulin-like growth factor I (IGF-I) improved the patient's hyperglycemia and corrected certain metabolic abnormalities over a 9-month period, even though the binding of 125I-labeled IGF-I to her cultured fibroblasts was decreased by 40% relative to that to cells from healthy controls. Studies of the binding of 125I-labeled insulin to the proband's cultured fibroblasts, to COS-I cells transfected with complementary DNA encoding the mutant insulin receptor, and to partially purified mutant receptors revealed that the Arg252-->His mutation decreased both cell surface expression and the affinity for insulin for the receptor. These observations suggest that the homozygous Arg252-->His mutation is responsible for the type A insulin resistance of the proband, whereas in the heterozygous state, the mutation results in mild insulin resistance indistinguishable from that observed in noninsulin-dependent diabetes mellitus.
The effects of hot water extracts and six compounds of N-containing sugars, 1-deoxynojirimycin (DNJ), N-methyl-DNJ (N-Me-DNJ), 2-O-alpha-D-galactopyranosyl-DNJ (GAL-DNJ), fagomine, 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), and 1,2 alpha,3 beta,4 alpha-tetrahydroxynortropane (calystegin B2), derived from mulberry leaves (Morus alba L.), were investigated on pilocarpine-induced saliva secretion in streptozocin (STZ)-induced diabetic mice. The extracts (100 and 200 mg/kg, i.p.) significantly potentiated the pilocarpine-induced salivary flow but not the protein content. The component compounds (37.5-300 mumol/kg) potentiated the saliva secretion, and the potency order was DAB > fagomine > GAL-DNJ. Only fagomine significantly increased the protein content in the saliva. The potentiation of pilocarpine-induced salivary flow was correlated with anti-hyperglycemic effects by the extract and GAL-DNJ from mulberry leaves in the same dose ranges.
Averaged blood glucose levels were 400 mg/dl in nonfasted mice, and 250 mg/dl in fasted mice in 4 weeks after injection with streptozotocin (STZ, 150 mg/kg, i.v.). These mice were used for experiments. Hypoglycemic effects of hot water extracts (W) from Folium Mori (Mulberry leaves, Morus alba L., China and Japan) or Cortex Mori Radicis (Morus alba L., China) were observed in fasted and nonfasted STZ-induced diabetic mice at a single dose of 200 mg/kg (i.p.). The W from Folium Mori exhibited most potent hypoglycemic effects. The most potent fractions of Folium Mori and Cortex Mori Radicis were ethanol-insoluble extracts (A2). These A2 fractions demonstrated a fall in blood glucose levels of 24.6 +/- 6.0% and 60.5 +/- 9.1% at nonfasted STZ-mice, and 81.4 +/- 7.9% and 77.3 +/- 5.8% at fasted STZ-mice, respectively. The increase in glucose uptake was a mechanism of hypoglycemic actions by W and A2 of Folium Mori.
We investigated the effects of the salivary peptide P-C (P-C), a saliva-derived peptide, on glucose (8.3 mM)- and arginine (10 mM)-induced insulin release and arginine (10 mM)-induced glucagon release using the perfused pancreas of spontaneously diabetic GK rats. Both its potentiating effect on insulin release and its inhibitory effect on glucagon release were concentration-dependent in diabetic GK rats. The ratio of insulin release obtained with P-C (194 nM) to that without P-C in GK rats was the same as ratio in normal Wistar rats. The ratio (0.40) of glucagon release obtained with P-C (194 nM) to that without P-C was smaller in diabetic GK rats than that (0.75) in normal Wistar rats. These results indicate that P-C inhibits arginine-induced glucagon release in diabetic GK rat pancreas more effectively than in normal Wistar rat pancreas.
The amino acid domains in salivary peptide P-C (1-44 peptide fragments, P-C) that are essential to potentiate insulin release and inhibit glucagon release were investigated using isolated perfused rat pancreas. P-C significantly potentiated not only glucose (8.3 mM)-induced insulin release, but also arginine (10 mM)-induced insulin release. The essential domain responsible for potentiation of insulin release was the P-C-(23-29) fragment, 23KPQGPPP29, while that inhibiting glucagon release was the P-C-(12-18) fragment, 12HQQGPPP18. Since both domains share a common fragment, QGPP, these findings indicate that the functional amino acid sequences KP and HQ may potentiate insulin release and inhibit glucagon release, respectively.
Fifty-one middle-aged male patients with obstructive sleep apnea syndrome (OSAS) were evaluated using two-dimensional echocardiography, 24-h blood pressure measurements, polysomnography, and plasma norepinephrine (NE) measurements. Among these patients, left ventricular hypertrophy (LVH) (left ventricular posterior wall thickness [LVPWT] or interventricular septal thickness [IVST] > or = 12 mm) and right ventricular hypertrophy (RVH) (right ventricular wall thickness [RVT] > or = 5 mm) were present in 41.2% (21/51) and 11.8% (6/51). LVH was present in 50.0% of group 2 patients (apnea index > or = 20) and in 30.5% of group 1 patients (apnea index < 20). All patients with LVH had hypertension. RVH was present in 21.4% of group 2 patients and none of the group 1 patients. IVST, LVPWT, LV mass, LV mass/body surface area (BSA), and obesity index were significantly greater in group 2 than in group 1. Apnea index and the duration in which nocturnal oxygen saturation was decreased under 90% (duration of SaO2 < 90%), were significantly correlated with LV mass/BSA and 24-h mean blood pressure. Apnea index, number of apneas, duration of nocturnal oxygen saturation less than 90%, weight, and obesity index were significantly greater in patients with both LVH and RVH than in patients without LVH and RVH, or those with only LVH. Plasma NE after waking significantly increased compared with that before sleep (p < 0.05). The ratio of plasma NE levels after waking to those before sleep was significantly correlated with the duration of SaO2 < 90% (r = 0.83, p < 0.05), but not with apnea index. These results suggest that frequent episodes of oxygen desaturation and/or arousal responses caused by apnea may contribute to the complication of LVH and RVH in the long term, and apnea-induced cyclical increases in blood pressure and the resulting sustained elevation in blood pressure associated with the increase in afterload and sympathetic activity may play a role in the development of LVH.
BACKGROUND: It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified. EXPERIMENTAL DESIGN: Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis. RESULTS: Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile. CONCLUSIONS: Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice.