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Biomedical subjects

Y Okuda

Publications and source records attributed to Y Okuda.

At least 19 recordsLinked to original sources
PubMed1996

Cloning and sequencing of a gene encoding a new member of the tetratricopeptide protein family from magnetosomes of Magnetospirillum magnetotacticum.

A gene encoding the 22 kDa protein (MAM22) which was localized in the magnetosomes isolated from the magnetotactic bacterium, Magnetospirillum magnetotacticum, was cloned and sequenced. MAM22 was composed of 220 amino acids (aa) with a molecular weight of 24,186 Da. The deduced aa sequence exhibited significant homology with a number of proteins that belong to the tetratricopeptide repeat (TPR) protein family, including mitochondrial protein import receptors and peroxisomal protein import receptors. The presence of three repeats of a degenerate 34-aa consensus sequence, suggest that MAM22 localized in magnetosome membranes may interact with the cytoplasmic proteins containing similar TPR motifs.

Amino Acid Sequence↗
PubMed1996

Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigmented epithelial cells.

Vascular endothelial growth factor (VEGF) is closely correlated to diabetic retinopathy. Its basal production in three types of cultured retinal cells (endothelial cells, pericytes and retinal pigment epithelial cells; RPE) was examined. RPE production of VEGF was markedly higher than the rest of the cells. VEGF production in RPE was significantly elevated by 10-day, but not by 1- or 3-day exposure to 16.5 mM glucose compared to a 5.5 mM glucose group. Transient deterioration of diabetic retinopathy is frequently observed during rapid correction of glycemic control. To determine whether VEGF is up-regulated following a sharp drop in the glucose concentration or not, we examined the changes in VEGF production in RPE before and after a sudden drop in the glucose concentration. VEGF production was significantly increased by a glucose concentration decrease from 5.5 to 0.5 mM, but not by a decrease from 33 or 16.5 to 5.5 mM. These findings suggest that up-regulation of VEGF may contribute to the development of diabetic retinopathy and its worsening by hypoglycemia.

Animals↗
PubMed1996

Progesterone induces vascular endothelial growth factor on retinal pigment epithelial cells in culture.

Diabetic retinopathy is known to frequently deteriorate during pregnancy but the cause remains obscure. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a potent vascular endothelial cell mitogen which is mainly up-regulated by hypoxia, and is closely associated with the development and progression of diabetic retinopathy. To examine the influence of the drastic hormonal alterations during pregnancy on the worsening of diabetic retinopathy, we examined the effects of estradiol (E2) and progesterone (P4) on the production of VEGF/VPF in bovine retinal pigment epithelial cells in culture. The VEGF/VPF production was significantly elevated (214.5 +/- 28.3 ng/g protein, P < 0.01) by 48 h of exposure to a high concentration of P4(10 microM), which is still within the physiological range during pregnancy, compared to that of the control group (147.7 +/- 17.9 ng/g protein). However, E2 significantly stimulated the production of VEGF/VPF only at concentrations (100 microM) much higher than normally encountered during pregnancy. These two hormones were not observed to have a synergistic effect, at least at physiological concentrations. As the increase in serum P4 levels during pregnancy is reported to be greater in pregnant diabetic patients with progressive retinopathy, our findings suggest that P4 may contribute to the worsening of diabetic retinopathy during pregnancy by up-regulating intraocular VEGF levels.

Animals↗
PubMed1996

Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic value of gastroduodenal biopsy.

Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA.

Amyloid↗
PubMed1996

Expression and regulation of neuropeptide Y messenger ribonucleic acid in cultured immature rat Leydig and Sertoli cells.

Neuropeptide Y (NPY) potentiates the release of gonadotropins from the pituitary in response to GnRH in the hypothalamus and modulates reproductive function. In the present study, we showed that 1) specific organs in the male rat reproductive tract express NPY messenger RNA (mRNA); 2) the multifactorial regulation of NPY mRNA in rat Leydig and Sertoli cells is temporally and hormonally regulated in vitro; 3) both Sertoli cell factor(s) and germ cell factor(s) potentiated to stimulate NPY gene levels in Leydig cells; and 4) intense NPY immunoreactivity was detected in cultured Leydig cells. Using the RT-PCR method, we found that Leydig cells, Sertoli cells, epididymis, and vas deferens expressed NPY mRNA, whereas germ cells, seminal vesicle, and prostate did not. Northern blot analyses showed that NPY mRNA was not expressed in freshly isolated immature Leydig cells, but that NPY mRNA levels were increased by the addition of LH, cytokines such as interleukin-1 alpha and -1 beta, forskolin, or phorbol 13-myristate 12-acetate. Npy mRNA levels in immature Sertoli cells were also increased by FSH. In addition, a germ cell factor(s) secreted from pachytene spermatocytes or round spermatids purified by centrifugal elutriation as well as a Sertoli cell factor(s) stimulated by FSH increased NPY gene levels in Leydig cells. Immunocytochemical analyses showed that the immunostaining was more marked in Leydig cells than in Sertoli cells in vitro. These findings indicate that testicular NPY gene expression is induced in Leydig cells or Sertoli cells by gonadotropins or cytokines within the testes, and that factors secreted from Sertoli cells or germ cells affect NPY gene expression in Leydig cells in vitro. Our findings suggest that NPY expressed in the reproductive system may modulate reproductive function as well as that in the nervous system.

Animals↗
PubMed1996

Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis.

Although a growing body of evidence supports that alkali therapy in diabetic ketoacidosis (DKA) might be counterproductive, our knowledge about the consequences of this treatment on ketone metabolism is limited. Consequently, we performed clinical and animal studies to further examine this topic. The clinical studies assessed seven patients with DKA treated with continuous insulin infusion at a low dosage. Three of them also received sodium bicarbonate (NaHCO3), whereas the remaining four acted as controls. The group receiving NaHCO3 showed a 6-h delay in the improvement of ketosis as compared with controls. In addition, there was an increase in acetoacetate (AcAc) levels during alkali administration, followed by an increase in 3-hydroxybutyrate (3-OHB) level after its completion. Significant differences were not found between groups in the response of plasma glucose to the overall therapy. The animal study examined the effects of a NaHCO3-rich perfusate on the hepatic production of ketones with the in situ rat-liver preparation. Alkali loading resulted in an immediate increase in the AcAc level followed by increases in both the 3-OHB level and the 3-OHB/AcAc ratio after its completion. Hepatic ketogenesis increased even further, to about twice the basal level, after termination of the NaHCO3 loading. This investigation confirms that alkali administration augments ketone production and unravels an effect of bicarbonate infusion that promotes a selective build up of AcAc in body fluids. The data support that alkali therapy in DKA has nonsaltuary effects in the metabolism and plasma levels of ketones.

Adult↗
PubMed1995

Mobilization of gastric histamine during repeated administration of a proton potassium adenosine triphosphatase inhibitor in intact and antrectomized rats.

Intact and antrectomized female rats were treated with the potent proton pump inhibitor, E3810 (daily 40 mg/kg weight, s.c.) for 4 weeks. Plasma gastrin concentration and urinary excretion of N-terminal big gastrin increased until day 14 and persisted at a high level in intact rats treated with E3810, but did not increase in antrectomized rats. Urinary excretion of histamine increased progressively and reached 7 times the control value following 4 weeks of treatment with E3810 in intact rats, but not in antrectomized rats. At the termination of the treatment, the endocrine cell density in the oxyntic mucosa of intact rats had increased by 85% with increased histamine content and elevated histidine decarboxylase activity, while antrectomized rats showed a low histamine level and low histidine decarboxylase activity. Administration of gastrin-17 I (10 micrograms/kg weight, sc) itself caused a significant increase in urinary excretion of histamine, which was inhibited by the specific gastrin receptor antagonist, L-365,260. These results suggests that the massive urinary excretion of histamine caused by the treatment with E3810 reflects gastrin-induced mobilization of gastric histamine and that neither E3810 itself nor E3810-induced luminal pH elevation has direct effects on mobilization of oxyntic mucosal histamine.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

High glucose increases platelet-derived growth factor production in cultured human vascular endothelial cells and preventive effects of eicosapentaenoic acids.

The regulation of the production of platelet-derived growth factor (PDGF) and the influence of high glucose concentration, eicosapentaenoic acid (EPA) were studied in cultured human umbilical vein endothelial cells (HUE). The PDGF production of HUE increased markedly depending on glucose concentration. However, EPA (3 x 10(-4)M) markedly inhibited PDGF production [27.5 mM glucose group: 123 +/- 3% of control (5.5 mM glucose group), 27.5 mM glucose+EPA group: 104 +/- 5% of control]. These results suggested that a high glucose concentration and a high osmotic pressure-induced increase in PDGF production is involved in the development and progression of diabetic macroangiopathy. As eicosapentaenoic acid inhibits the PDGF production induced by high glucose concentration in HUE, use of this agent may exhibit anti-arteriosclerotic effects.

Cells, Cultured↗
PubMed1995

Restoration of myo-inositol uptake by eicosapentaenoic acid in human skin fibroblasts cultured in high-glucose medium.

The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) on myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol incorporation into HSF was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate some of the devastating functions associated with diabetes.

Cells, Cultured↗
PubMed1995

Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis.

A cytokine-mediated excessive increase in nitric oxide (NO) by macrophages or glial cells via an inducible isoform of NO synthase (iNOS) has been proposed to play an important role in demyelinating diseases. To further investigate the role of iNOS in demyelination, experimental allergic encephalomyelitis (EAE), a known animal model of multiple sclerosis (MS) in mice, was chosen in this study. A semiquantitative reverse transcriptase-polymerase chain reaction (RT/PCR) analysis revealed an increase in the mRNA levels of iNOS and cytokines known to induce iNOS or inflammatory cytokines (interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-6, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta) in the spinal cord corresponding to the severity of the disease without significant change in the mRNA levels of immunoregulatory cytokines (IL-4, IL-10 and transforming growth factor (TGF)-beta) during the course of EAE. An immunohistochemical examination of the spinal cord using an iNOS-specific antibody showed iNOS-positive cells to be mainly inflammatory cells with a higher frequency of iNOS-positive cells at the peak of EAE than in the early phase. These iNOS-positive cells at the peak appeared to be composed of infiltrating macrophages and most of them were located in the necrotic area. These results suggested that cytokine-induced excessive NO via iNOS by macrophages caused tissue damage in the central nervous system in EAE.

Animals↗
PubMed1995

Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism.

Tay-Sachs and Sandhoff diseases are clinically similar neurodegenerative disorders. These two sphingolipidoses are characterized by a heritable absence of beta-hexosaminidase A resulting in defective GM2 ganglioside degradation. Through disruption of the Hexa and Hexb genes in embryonic stem cells, we have established mouse models corresponding to each disease. Unlike the two human disorders, the two mouse models show very different neurologic phenotypes. Although exhibiting biochemical and pathologic features of the disease, the Tay-Sachs model showed no neurological abnormalities. In contrast, the Sandhoff model was severely affected. The phenotypic difference between the two mouse models is the result of differences in the ganglioside degradation pathway between mice and humans.

Animals↗
PubMed1995

Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage.

Pathophysiological mechanisms for vasospasm after subarachnoid haemorrhage (SAH) remain unclear and, so far, roles of cytokines in vasospasm have not been known. In the present study, we measured interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-alpha (TNF-alpha) concentrations in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH). ELISA assay were performed on 21 CSF samples from 7 patients with SAH and on 4 sera samples. Both IL-6 and IL-8 were detected in all CSF samples, but IL-1 alpha, IL-1 beta, and TNF-alpha were not detected. IL-6 and IL-8 were also detected in sera, but at much lower concentrations. This study indicates that IL-6 and IL-8 may play roles as immunomodulators in patients with SAH. In addition, it has been reported that IL-6 inhibits prostaglandin I2 production and increases the mRNA level of c-sis gene, suggesting that IL-6 may play an important role in vasospasm as vasoconstrictor.

Aged↗
PubMed1995

The effect of nilvadipine on bloodflow in the dorsal pedis artery in type 2 diabetic patients--a study using duplex Doppler ultrasonography.

The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo. Pulse rate and blood pressure were measured simultaneously. There were no significant changes in pulse rate or blood pressure after administration of either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm2, p < 0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p < 0.05) were significantly increased in the treatment group, whereas there were no significant changes in either measurement in the control group. The findings showed that a single administration of nilvadipine increases blood flow in the dorsal pedis arteries of diabetic patients.

Arteries↗
PubMed1995

Transient nephrogenic diabetes insipidus accompanied by possible psychogenic polydipsia.

A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms. His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head. Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP. The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case.

Arginine Vasopressin↗
PubMed1995

Efficacy of Ibudilast on lower limb circulation of diabetic patients with minimally impaired baseline flow: a study using color Doppler ultrasonography and laser Doppler flowmetry.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

Administration, Oral↗