Effects of cholesterol-lowering treatments on oxidative modification of plasma intermediate density lipoprotein plus low density lipoprotein fraction in Type 2 diabetic patients.

To investigate the normalization of enhanced oxidative modification of the lipoprotein such as increased lysophosphatidylcholine (LPC) and lipid hydroperoxide (LPO) contents in diabetic subjects, we studied the effect of cholesterol-lowering treatment on those parameters in 24 hypercholesterolemic Type 2 diabetic patients. Those patients were randomly assigned to two treatment groups, such as 12 patients treated with pravastatin 10 mg daily and 12 patients treated with probucol 500 mg daily for 8 weeks. Characteristics of the patients including age, gender, body mass index (BMI), smoking habit, modality of diabetic treatment and the glycemic control state were comparable between the two groups.

[Molecular mechanism and clinical impact of insulin resistance in type 2 diabetes mellitus].

Type 2 diabetes is characterized by insulin resistance as well as impaired insulin secretion. Thus, the enhancement of insulin sensitivity is a possible treatment modality. The mechanism of insulin resistance is still unknown.

A new antidiabetic agent (JTT-501) rapidly stimulates glucose disposal rates by enhancing insulin signal transduction in skeletal muscle.

A newly synthesized antidiabetic agent, JTT-501 is an isoxazolidinedione rather than a thiazolidinedione. An oral dose of JTT-501 (100 mg x kg(-1) x day(-1)) given to 12-week-old male Zucker fatty rats for 7 days led to the amelioration of both hyperinsulinaemia (40% of non-treated) and hypertriglyceridaemia (23% of non-treated) as well as a 2.4-fold increased insulin sensitivity as determined by a euglycaemic insulin clamp.

Role of somatosensory feedback from tools in realizing movements by patients with ideomotor apraxia.

In order to investigate the underlying mechanism of ideomotor apraxia, we studied 9 patients who could not mime using tools despite the ability to manipulate actual tools normally. In all the mime tasks, visually presented tools or model gestures by examiners were fundamentally ineffectual in improving the patients' performances. Even the remarkable improvement demonstrated when using actual tools disappeared immediately after the subjects took their hands off them.

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty rats.

Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats.

Treatment of metastatic nonseminomatous germ cell tumors of the testis: significance of the international consensus prognostic classification as a prognostic factor-based staging system.

Background: We reviewed treatment results in patients with metastatic nonseminomatous germ cell tumors of the testis and examined the significance of the International Consensus Prognostic Classification to make appropriate risk-based decisions concerning induction chemotherapy.

Methods: We divided 37 patients treated with platinum-based combination chemotherapy into good, intermediate, and poor prognostic groups utilizing the International Consensus Prognostic Classification. The data was analyzed for both overall survival and progression-free survival among the 3 prognostic groups.

Opposite regulation of tyrosine-phosphorylation of p130(Cas) by insulin and insulin-like growth factor I.

To investigate the difference in signaling between insulin and insulin-like growth factor I (IGF-I), we studied the effects of these hormones on the phosphorylation state of Crk-associated substrate (Cas) in cells expressing human insulin receptor (HIRc). In the basal state, Cas was heavily tyrosine-phosphorylated, and insulin dephosphorylated Cas in a time- and dose-dependent manner. On the other hand, IGF-I phosphorylated rather than dephosphorylated Cas in HIRc cells.

Expression and activity of cyclin-dependent kinase 5/p35 in adult rat peripheral nervous system.

In spite of the clarification in the temporal and spatial expression pattern of a cyclin-dependent kinase (Cdk) 5 and its neuron-specific activator, p35, in the CNS, it remains to be elucidated in the PNS. In addition, it is not known whether Cdk5 activity exists in the PNS. Therefore, we have examined their expression and activity in the PNS by immunoblot analysis, immunohistochemistry, and in vitro kinase assay.

Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats.

Amnesia after a discrete basal forebrain lesion.

Destructive lesions of the basal forebrain are often associated with memory impairment and this structure is thought to contribute to memory function by providing a cholinergic input to critical structures associated with memory such as the hippocampus and amygdala. In previously reported cases of amnesia associated with damage in the basal forebrain, multiple neuroanatomical regions were damaged, and the critical lesion responsible for amnesia has not been identified clearly. We report a patient who developed primarily anterograde amnesia after clipping of an unruptured anterior communicating artery aneurysm.

High glucose-induced abnormal epidermal growth factor signaling.

We have reported that high glucose conditions (27 mM for 4 days) induces activation of protein tyrosine phosphatases (PTPases) which are associated with impaired insulin signaling in Rat 1 fibroblasts expressing human insulin receptors [Maegawa, H. et al. (1995) J.

Concerted regulation of early enterocyte differentiation by insulin-like growth factor I, insulin, and transforming growth factor-beta1.

To clarify the roles of insulin on the proliferation and differentiation of intestinal epithelial cells (IECs), we examined the effect of insulin-like growth factor-I (IGF-I) and insulin for the growth and differentiation of IEC-6 cells, a crypt cell line derived from rat small intestine. IGF-I (100 nM) stimulated the proliferation of IEC-6 cells, and insulin (1-100 nM) antagonized the IGF-I effect and caused the cells' G1-arrest, resulting in differentiated characteristics of IECs, such as increased general protein synthesis and the formation of microvilli. To clarify the mechanisms of these phenomena, cell surface [125I]insulin binding and the content of immunoreactive insulin receptors were analyzed by Western blotting.

5-fluorouracil and low-dose recombinant interferon-alpha-2a in patients with hormone-refractory adenocarcinoma of the prostate.

Background: The effectiveness of a chemotherapy regimen including 5-fluorouracil (5-FU) and recombinant interferon-alpha-2a (rIFN-alpha-2a) was evaluated in hormone-refractory prostate cancer patients.

Methods: Patients received a continuous intravenous infusion of 5-FU at 600 mg/m2/day for 5 days (D1-D5), followed by a bolus injection of 5-FU on D15 and D22. Patients received intramuscular injection of rIFN-alpha-2a at 3 million IU on D1, D3, D5, D15, and D22.

Inhibitor and temperature effect on catalase in the liver of adult diploid and haploid Rana rugosa.

The authors succeeded in raising a single mature haploid Rana rugosa female to the age of 2 years from an egg artificially fertilized with ultraviolet-irradiated sperm. In order to discover why this particular haploid individual should survive so long, hydrogen peroxide detoxifying catalase in the liver of this individual and age-matched diploids was examined and compared for total activity, temperature stability, and chemical inhibition. Total activity was found to be significantly higher in the haploid frog than in the diploids, suggesting that this particular haploid had a unique system for hydrogen peroxide detoxification which protected the liver against cell death, preventing hepatic failure, and leading to a prolonged survival.

Stage-dependent distribution of calreticulin in oocytes of the frog, Rana rugosa.

We studied immunohistologically the distribution of a Ca2(+)-binding protein, calreticulin (CLT), at different stages of growing oocytes in the frog, Rana rugosa. Northern blot analysis showed that the CLT gene expression in gonads of metamorphosing tadpoles was low, but was extremely strong in the ovary, but not in the testis, of 2-month post-metamorphosis frogs, followed by decline to a lower level in adult frogs. On the contrary, the beta-actin gene expression did not increase in the same ovary.

Molecular cloning and expression of the KIF3A gene in the frog brain and testis.

KIF3A is a member of the kinesin superfamily proteins (KIFs), but its gene has been cloned only in mouse and sea urchin. We have cloned a homolog of KIF3A from the frog, Rana rugosa (rrKIF3A). The sequence encoded a 699 amino acid protein that shares 93% similarity with mouse KIF3A (mKIF3A) and 69% with sea urchin kinesin-related protein (SpKRP85).

Comparison of catalase in diploid and haploid Rana rugosa using heat and chemical inactivation techniques.

The present study examines differences in the hydrogen peroxide (H2O2) detoxifying enzyme, catalase, found in the tails and livers of diploid and haploid Rana rugosa. Investigative techniques include measurement of catalase activity and tests for temperature stability and chemical inhibition. Catalase from the tails of pre-climactic (stage XXIII) haploids was found to be over three times as H2O2 destructive as catalase from similar tails of diploids.

Molecular cloning of cDNA for the zeta isoform of the 14-3-3 protein: homologous sequences in the 3'-untranslated region of frog and human zeta isoforms.

14-3-3 proteins constitute a family of well-conserved eukaryotic proteins that possess diverse biochemical activities such as regulation of gene transcription, cell proliferation and activation of protein kinase C. At least 7 subtypes (alpha to theta) of 14-3-3 protein are known, but the zeta subtype of this protein has been cloned only in mammals. We cloned the zeta subtype of 14-3-3 protein (14-3-3 zeta) from the frog, Rana rugosa.

Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.

Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP.

Cilostazol, a cAMP phosphodiesterase inhibitor, attenuates the production of monocyte chemoattractant protein-1 in response to tumor necrosis factor-alpha in vascular endothelial cells.

The induction of monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial cells is thought to be an initial event in the development of atherosclerotic lesions. Therefore, inhibition of MCP-1 production may exhibit some effects in preventing atherosclerosis. In the present study, we found that 10 microM cilostazol, a cAMP phosphodiesterase inhibitor, increased the intracellular cAMP content by a twenty-five times of the basal level and resulted in the reduction of basal MCP-1 release by 41% from 168 +/- 11 ng/24 hr/mg protein to 99 +/- 14 ng/24 hr/mg protein (P < 0.

Pyruvate improves deleterious effects of high glucose on activation of pentose phosphate pathway and glutathione redox cycle in endothelial cells.

In our previous study (Diabetes 44:520-526, 1995), endothelial cells cultured in high glucose condition showed impairment of an oxidant-induced activation of the pentose phosphate pathway (PPP) and a reduced supply of NADPH to the glutathione redox cycle. To gain insight into the mechanisms of this impairment, the protective effect of pyruvate was studied in human umbilical vein endothelial cells cultured in either 5.5 mmol/l glucose (normal glucose [NG] condition) or 33 mmol/l glucose (high glucose [HG] condition).

Evidence for two successive pericentric inversions in sex lampbrush chromosomes of Rana rugosa (Anura: Ranidae).

The objective of this study was to clarify the course of inversions by which a ZW sex chromosome dimorphism has become established in Rana rugosa. Fortunately, R. rugosa preserves three different forms of sex chromosomes in the several isolated populations.

Diabetic lipemia with maturity-onset diabetes of the young.

A 19-year-old woman with diabetic lipemia and maturity-onset diabetes of the young (MODY) is reported. Though her insulin secretory activity was preserved, she fell into mild diabetic ketoacidosis (DKA) and showed type V hyperlipidemia. Post-heparin plasma activity of lipoprotein lipase (LPL) was decreased even 10 days after initiating insulin injection but not deficient.