Search PubMed⌕ Search

Biomedical subjects

Y Okuda

Publications and source records attributed to Y Okuda.

At least 199 records · Page 11Linked to original sources
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

Effect of cilostazol on the production of platelet-derived growth factor in cultured human vascular endothelial cells.

Increased levels of platelet-derived growth factor (PDGF) may play a central role in the development of arteriosclerosis, but the factors that inhibit PDGF production in vascular endothelial cells remain mostly unknown. We examined the effects of cilostazol, an antithrombotic agent, and high glucose on PDGF production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC grown in high glucose exhibits increased PDGF production, which was markedly inhibited by cilostazol. Since cilostazol inhibits PDGF production in HUVEC, its use may exhibit anti-arteriosclerotic effects in diabetic patients.

Cells, Cultured↗
PubMed1996

Nasal mucosal thickening simulating a tumor: potential for misdiagnosis in brain perfusion imaging.

A 33-year-old, female presenting with dementia was admitted to our institution. Except for slight muscle atrophy noted on both lower extremities there were no other significant physical signs or laboratory findings. Since initial Tc-99m HMPAO SPECT showed hypoperfusion on both temporal, parietal and occipital lobes, follow up study with the same radiotracer was done. Increase in uptake was noted in the left side of the face. There was no abnormality noted on ENT examination. CT scan and MRI showed slight nasal mucosal wall thickening. T1-201 SPECT showed increased uptake in the nasal area. The increase in uptake could be due to nasal mucosal thickening. This could simulate nasal tumor and interfere in determining ROI for brain perfusion studies.

Adult↗
PubMed1996

Effects of high glucose concentration and a thromboxane synthase inhibitor on the production of thromboxane A2 and prostaglandin I2 and E2 by retinal endothelial cells.

To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2) and the effects of a thromboxane synthase inhibitor (TXSI; KDI-792; 5Z-6[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridyl methyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1 alpha as an index of PGI2. The levels of TXA2 and PGI2 were 182.3 +/- 34.3 pg/mg and 336.7 +/- 36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1 +/_ 29.7 pg/mg and 511.4 +/- 65.8 pg/mg protein at 33 mM glucose (mean +/- SD, P<0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.

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

Increased production of PDGF by angiotensin and high glucose in human vascular endothelium.

The mechanisms responsible for the abnormalities in the vascular wall associated with long standing diabetes mellitus are incompletely understood. The aim of this investigation was to assess the effects of angiotensin II and high glucose on the production of platelet-derived growth factor (PDGF) in human endothelial cells. For this purpose, a primary culture was obtained from fresh human umbilical cords by collagenase digestion of the vein interior. A high glucose medium increased the production of PDGF and a similar effect was observed by the addition of mannitol. These data are consistent with a stimulatory effect of glucose on PDGF that is mediated by the osmotic effect of this substance. Angiotensin II significantly increased PDGF in human endothelial cells and the effect was accompanied by a transient increase in cytosolic calcium. The angiotensin II-induced intracellular Ca2+ increases, PDGF production were completely abolished by saralasin and neomycin, respectively. We postulate that the increased production of PDGF by the vascular endothelium in response to high glucose and angiotensin II may participate in the development of the diabetic angiopathy.

Angiotensin II↗
PubMed1996

Nitric oxide induces apoptosis in mouse splenic T lymphocytes.

The cytotoxic effect of nitric oxide (NO) on mouse T lymphocytes was investigated. Freshly isolated T lymphocytes from mouse spleen were incubated with NOR, a novel NO releasing agent, at different doses. After incubation for 4 h, apoptotic cell death was observed in both NOR-treated T lymphocytes and controls as judged by the appearance of DNA laddering in agarose gel electrophoresis, but a quantitative analysis by flow cytometry indicated that the high level of exogenous NO (500 micrograms ml of NOR) could promote apoptosis in T lymphocytes as compared with controls (30% vs. 8%). After 8 h, NO promoted apoptosis of T lymphocytes in a dose-dependent manner. This study indicated that NO might be one of the factors which regulate this life of T lymphocytes in vivo.

Animals↗
PubMed1996

Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry.

The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I- octen-6-ynyl] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner 40 micrograms) and elastase (Elaszym 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

Arteries↗
PubMed1996

Pentoxifylline delays the onset of experimental allergic encephalomyelitis in mice by modulating cytokine production in peripheral blood mononuclear cells.

The effect of pentoxifylline (PTX) on experimental allergic encephalomyelitis (EAE) in mice, a known animal model of multiple sclerosis (MS), was investigated. PTX was orally administrated at 10, 40 and 100 mg/kg/day, respectively. Although oral PTX at these doses had no significant effect on the incidence and severity of EAE, oral PTX (40 mg/kg/day) alone produced a significant delay in the onset of EAE. Semiquantitative reverse transcriptase-polymerase chain reaction analysis revealed that PTX at this dose reduced the mRNA levels for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in peripheral blood mononuclear cells (PBMC) of mice with EAE. A histopathological study showed that PTX treatment delayed infiltration of inflammatory cells in the central nervous system (CNS) of mice with EAE. These results indicated that the tolerable dose of PTX had a suppressive effect on the induction phase of EAE by modulating cytokine production in PBMC but had no effect on the severity of EAE. The findings in the present study with animals suggested that a tolerable dose of PTX might prolong the intervals between relapses in MS, but might not improve the clinical sign and symptoms of MS.

Animals↗
PubMed1996

Predicting long-term glycemic control of post-educational type II diabetic patients by evaluating serum 1,5-anhydroglucitol levels.

1,5-Anhydroglucitol (1.5-AG) is known to closely reflect diabetic control within several days. The possibility of predicting long-term glycemic control after an educational hospitalization of type II diabetic patients was investigated by examining the relationship between changes in serum 1,5-AG levels after a short-term trial home stay following an educational program and long-term changes in glycosylated hemoglobin A1c (HbA1c) levels after discharge. After 22 patients with type II diabetes had successfully completed the educational hospitalization program, they returned as outpatients for 5 nights in a row. Changes in serum 1,5-AG levels were determined during this period. The HbA1c levels were then determined over a period of 3 months after discharge, and the relationship between changes in 1,5-AG and HbA1c levels was examined. Changes in serum 1,5-AG levels during the 5-day trial home stay and the changes in HbA1c levels during the 3 months after discharge from the hospital were found to be significantly correlated (r = 0.70, P < 0.01). A comparison of the decreased group, which exhibited a decrease in 1.5-AG levels of 5.0 mumol/l or more during the trial home stay, and the unchanged group, revealed that increases in body mass index 3 months after discharge were significantly higher in the decreased group (1.2 +/- 0.4%) than in the unchanged group (0.2 +/- 0.5%) (P < 0.05). Determination of serum 1,5-AG levels of patients with type II diabetes before and after a trial home stay following educational hospitalization was found to be useful in identifying patients at high risk of recurrence of poor glycemic control in the future.

Aged↗
PubMed1996

IFN-gamma in combination with IL-3 accelerates platelet recovery in mice with 5-fluorouracil-induced marrow aplasia.

The effects of interferon-gamma (IFN-gamma) on platelet recovery were examined in mice with marrow aplasia induced by i.p. injection of 250 mg/kg of 5-fluorouracil (5-FU). The cytokine was administrated by microosmotic pump, with an ability to deliver a consistent intact dose of cytokine for 7 consecutive days. Administration of 250 IU/kg/day of IFN-gamma in combination with 10(3) U/kg/day of IL-3, which alone had no effect on platelet counts, diminished the nadir for platelet count and shortened the duration of thrombocytopenia. The effect was comparable to that of higher doses of IL-3 (10(5) U/kg/day). The administration of 250 IU/kg/day of IFN-gamma in combination with 10(3) U/kg/day of IL-3 also induced megakaryocyte proliferation in bone marrow cell cultures. Single administration of either 250 IU/kg/day of IFN-gamma or 10(3) U/kg/day of IL-3 had no significant effects. The effect of this combination was also comparable to that of a higher dose of IL-3 (10(5) U/kg/day). We suggest that IFN-gamma accelerates megakaryocyte development, which leads to platelet production in chemotherapy-induced marrow aplasia. The administration of IFN-gamma in combination with IL-3 might be useful for the management of marrow aplasia.

Anemia, Aplastic↗
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

Gallbladder cancer with a low junction of the cystic duct or an anomalous pancreaticobiliary junction.

OBJECTIVE: To evaluate conditions similar to those of carcinogenesis of the gallbladder between the gallbladder with a low junction of the cystic duct (LJCD) and an anomalous pancreaticobiliary junction (APBJ). DESIGN: Retrospective and clinicopathological analysis of patients with gallbladder carcinoma. SETTING: First Department of Surgery, Kansai Medical University. PATIENTS: Examination of 47 patients (7 men and 40 women; average age: 67.8 years) with gallbladder carcinoma revealed 7 patients (14.9%; 1 man and 6 women; average age: 67.8 years) with LJCD and 6 patients (12.8%; 6 women; average age: 60.3 years) with APBJ. METHODS: Clinical findings in both groups were compared with those of the 34 patients who remained after exclusion of the data of the above 7 patients with LJCD and 6 patients with APBJ. The data of the three groups were examined by the chi 2 test at the 5% level of significance. RESULTS: Most of the gallbladder cancer patients with LJCD or APBJ had gallstones. The biliary amylase levels determined in the gallbladder of patients with LJCD or APBJ were remarkably high. CONCLUSION: The results indicate that patients with LJCD or APBJ are more likely to develop carcinoma of the gallbladder. The factors responsible for carcinogenesis may be alteration of the bile content due to reflux of pancreatic enzymes through the LJCD or APBJ, and mechanical irritation due to gallstones. Therefore, these pathological conditions in patients with LJCD are similar to those experienced in patients with APBJ.

Aged↗
PubMed1996

Radioiodinated metaiodobenzylguanidine scintigraphy for pheochromocytoma. A false-positive case of adrenocortical adenoma and literature review.

Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a 'silent' or 'asymptomatic' pheochromocytoma.

3-Iodobenzylguanidine↗
PubMed1996

A case of renovascular hypertension with marked polyuria after percutaneous transluminal renal angioplasty.

A 43-year-old female patient with hypertension was diagnosed as having one-kidney renovascular hypertension with dysfunction of the contralateral kidney, and percutaneous transluminal renal angioplasty was carried out. Marked polyuria was observed during the 2- to 72-hour postoperative period. During the 12- to 18-hour period of polyuria, the urine volume was 8.9 liters/6 h, which was 62% of the glomerular filtration, and was accompanied by high fractional excretion of sodium and of potassium and a high urine beta 2-microglobulin level. The mechanism of polyuria in this case is discussed.

Adult↗
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↗