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Biomedical subjects

Y Kato

Publications and source records attributed to Y Kato.

At least 235 records · Page 13Linked to original sources
PubMed2001

Effect of insulin on nitric oxide synthase-like immunostaining of arteries in various organs in Zucker diabetic fatty rats.

OBJECTIVE: Recently we reported that insulin treatment improved hypertension by inducing nitric oxide synthase (NOS) in Zucker diabetic fatty (ZDF) rats. In the present study, we investigated subtypes of NOS induced by insulin in arteries in various organs of ZDF rats using immunohistochemistry. DESIGN: Following treatment with insulin, localization of two subtypes of NOS in the arterial tissues of various organs was identified. METHODS: Following 4 weeks of s.c. injection of insulin, the aorta, cerebral cortex, pancreas and kidney were stained with polyclonal anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies. RESULTS: In the aortic tissue, eNOS-like immunostaining was observed equally in the insulin-treated group and the control group, whereas iNOS-like immunostaining was present more densely in the insulin-treated group. In the cerebral artery, eNOS-like immunostaining was observed in the endothelium and was enhanced in the insulin-treated group. In the control group, iNOS-like immunostaining was absent in the cerebral artery, whereas immunostaining was densely observed in the insulin-treated group. In the interlobular artery of the pancreas, both eNOS-like and iNOS-like immunostaining was present in the control group and was enhanced in the insulin-treated group. In kidney, both eNOS-like and iNOS-like immunostaining was more densely present in the arterial tissue of the insulin-treated group. CONCLUSIONS: These results taken together suggest that insulin treatment induced NOS in arteries in various organs and that iNOS was more strongly induced than eNOS by insulin treatment in the ZDF rat.

Animals↗
PubMed2001

Full-term development of enucleated mouse oocytes fused with embryonic stem cells from different cell lines.

The developmental potential of enucleated mouse oocytes receiving embryonic stem cells from ten lines with either the same or different genetic backgrounds using the cell fusion method was examined in vitro and in vivo. The development of nuclear-transferred oocytes into blastocysts was high (34-88%). However, there was no clear correlation between development into blastocysts after nuclear transfer and the chimaera formation rate of embryonic stem cells. The development into live young was low (1-3%) in all cell lines and 14 of 19 young died shortly after birth. Most of the live young had morphological abnormalities. Of the five remaining mice, two died at days 23 and 30 after birth, but the other three mice are still active at days 359 (mouse 1) and 338 (mice 4 and 5) after birth, with normal fertility. However, the reasons for the abnormalities and postnatal death of embryonic stem cell-derived mice are unknown.

Animals↗
PubMed2001

Expression of endothelial nitric oxide synthase gene in cultured porcine granulosa cells after FSH stimulation.

The present study was designed to investigate nitric oxide (NO) synthesis and the expression of endothelial NO synthase (eNOS) gene in cultured porcine granulosa cells. Granulosa cells prepared from small follicles (1-4 mm diameter) were cultured in plastic dishes coated with fibronectin in chemically defined medium, and matured after 48 h of stimulation with FSH. The concentrations of nitrite and nitrate remained relatively constant until 42 h of stimulation, after which they increased significantly up to twofold at 48 h. NO synthesis was accompanied by an increase in cGMP. Gene expression for eNOS was studied by RT-PCR, and a PCR product of the expected size amplified. eNOS mRNA was expressed in the presence of FSH, but not in the absence of FSH. Although eNOS mRNA was not expressed in the initial period, it was expressed after 12 h of stimulation with FSH, and remained at a relatively constant level until 48 h. Expression of eNOS mRNA preceded expression of LH receptor mRNA, which showed a maximal level at 24 h of stimulation. These observations suggest that eNOS expression is not related to a rapid synthesis of NO in developing granulosa cells, and that the activation of NO synthesis is rigidly regulated in the initial period of development.

Animals↗
PubMed2001

A possible relationship between abortions and placental embolism in pregnant rabbits given human granulocyte colony-stimulating factor.

Developmental toxicity studies were conducted in rats and rabbits with a human G-CSF derivative (NTG). As reported for G-CSF, increases in abortions and fetal mortality were observed in rabbits, but not in rats given NTG. Histopathological examination of the rabbit placenta revealed accumulation of neutrophils in vessels and necrosis of the tissues surrounding these vessels. To assess the mechanism of abortion and fetal death in rabbits given G-CSF, 125I-labeled NTG was given intravenously on Day 18 of pregnancy after repeated administration of cold NTG on Days 6 through 17 of pregnancy, and the feto-maternal distribution of radioactivity was examined. In a rabbit given 20 micrograms/kg, high radioactivity was observed in the endometrium, placenta, and some parts of the decidua at 6 hr when the concentration of radioactivity in maternal blood had already decreased. At 24 hr after administration of 200 micrograms/kg NTG, high radioactivity was still detected in parts of the maternal placenta. These patterns of distribution suggest that embolism occurred in parts of the uterus and placenta which might have caused congestion. Radioactivity in the TCA precipitates in the fetus was low, suggesting that NTG does not readily transfer to the fetus. These results strongly suggest that neutrophils accumulated in the vessels of placenta and induced embolism leading to abortions and fetal mortality in the rabbits given G-CSF.

Absorption↗
PubMed2001

Malignant lymphoma of the bone associated with systemic sarcoidosis.

A 57-year-old woman was hospitalized with malignant lymphoma of the right talus. After treatment, complete remission was obtained. Gallium-67 scintigraphy to confirm the remission demonstrated increased uptake in the whole body skeletal muscle, especially in her thighs. Biopsy of right gastrocnemius muscle showed epithelioid granuloma. Serum angiotensin-converting enzyme activity (ACE) and lysozyme had increased to several times the normal range. We diagnosed her disease as bone-associated sarcoidosis-lymphoma syndrome. Human herpes virus 8 (HHV-8) genome was examined in the bone marrow specimen, and the relationship between sarcoidosis-lymphoma syndrome and HHV-8 was discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Clinical features of fulminant hepatitis in Nagasaki Prefecture, Japan.

OBJECTIVE: Fulminant hepatitis is a rare but fatal disease. In the present study, we examined the changes in etiology and prognosis of fulminant hepatitis in Nagasaki Prefecture, Japan between 1980 to 1999. METHODS: Eighty-one patients with fulminant hepatitis admitted to our hospitals from 1980 to 1999 were examined with respect to the etiology and prognosis. RESULTS: Fulminant hepatitis was due to hepatitis A virus in 2 (12%) cases, hepatitis B virus in 18 (22%) cases, unknown etiology in 50 (62%) cases, and drug-induced in 11(14%) cases. The number of cases in the first half of the study (1980-1989) was 47 and that of the latter half (1990-1999) was 34 cases. The incidence of fulminant hepatitis type B also decreased from 14 cases (30%) to 4 cases (12%) during these periods. The overall survival rate of fulminant hepatitis was 32%; it was equal in fulminant hepatitis type B, fulminant hepatitis of unknown etiology and fulminant drug-induced hepatitis. The survival rate of fulminant hepatitis type A was 100%, though only two cases were identified. Retrospectively, the survival rate in patients with a pre-encephalopathy period of < or = 10 days and aged < or = 39 years was significantly higher than in patients > or = 40 years of age (p<0.01). There was no difference between the two age groups when pre-encephalopathy period was > or = 11 days. CONCLUSIONS: The incidence of fulminant hepatitis especially that of fulminant hepatitis type B in Nagasaki Prefecture has decreased in recent years. The survival rate is significantly higher in younger patients with a short pre-encephalopathy period.

Adolescent↗
PubMed2001

A combination analysis of p53 and p21 in gastric carcinoma as a strong indicator for prognosis.

We studied p53 and p21 expression simultaneously in gastric carcinoma tissues to investigate the clinical significance of p53-p21 pathway in this disease. One hundred sixty-four primary gastric carcinoma specimens were immunohistochemically stained for p53 and p21 protein, and clinicopathological features of the cases were examined. P53 was stained negatively, while p21 was stained positively in each normal stomach epithelium. P53, and p21 positive staining was observed in 82 (50%) and 61 (37.2%) tumors, respectively. Unexpectingly, no correlation was found between p53 and p21 staining status. Tumors demonstrating preserved p53-p21 pathway [p53(-)/p21(+)], observed in 20.1% of the tumors, displayed less aggressive characteristics, and no recurrent disease after curative resection. While tumors demonstrating disrupted p53-p21 pathway [p53(+)/p21(-)], observed in 32.9% of the tumors, displayed significantly more aggressive characteristics, poorer survival and higher recurrence rate than the tumors demonstrating other staining patterns. P53-p21 pathway was widely altered in gastric carcinomas. The combined evaluation of p53 and p21 expression in gastric carcinoma tissues is suggested to have clinical importance by indicating not only the malignant potential of each tumor, but also the prognosis of this disease.

Adenocarcinoma↗
PubMed2001

Proliferating cell nuclear antigen labeling index and p53 expression predict outcome for breast cancer patients with four or more lymph node metastases.

In general, extensive lymph node metastasis indicates poor prognosis in breast cancer. Nevertheless, some patients with this condition survive for a long time without recurrent disease. This study involved 112 breast cancer patients with four or more lymph node metastases and without distant metastasis who underwent surgery. p53 expression was associated with shorter overall and disease-free survival. High PCNA labeling index was associated with shorter overall disease-free survival. p53-negative and low-PCNA patients survived much longer than p53-positive and high-PCNA patients. This study showed that p53-negative or low-PCNA index patients have relatively good prognoses despite extensive lymph node metastasis.

Adult↗
PubMed2001

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2001

CJ-19,784, a new antifungal agent from a fungus, Acanthostigmella sp.

A new antifungal agent, CJ-19,784 (I), was isolated from the fermentation broth of a fungus, Acanthostigmella sp. CL12082. Based on spectroscopic analyses, structure of I was determined to be 3'-bromo-2',5-dihydroxy-3,7,8-trimethoxy-flavone. Compound I inhibits the growth of pathogenic fungi, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus with IC50 values of 0.11, 20 and 0.54 microg/ml, respectively.

Antifungal Agents↗
PubMed2001

Cytokine production inhibitors produced by a fungus, Oidiodendron griseum.

A series of diterpenes were isolated from the fermentation broth of a fungus, Oidiodendron griseum CL37215. The diterpenes were identified as LL-Z1271alpha, LL-Z1271gamma, CJ-14,445, PR 1388, CJ-14,604 and a new diterpene, CJ-14,515. They inhibited both lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production in human whole blood with IC50s of the range from 0.049 to 100 microM.

Ascomycota↗
PubMed2001

Novel cytokine production inhibitors produced by a basidiomycete, Marasmiellus sp.

New cytokine production inhibitors, CJ-14,877 (I) and CJ-14,897 (II), were isolated from the fermentation broth of a basidiomycete, Marasmiellus sp. CL21624. Their structures were determined to be methyl-(7S,8S)-5-(7,8-dihydroxypropyl)pyridine-2-carboxylate and methyl-(7S,8S)-5-(8-acetoxy-7-hydroxypropyl)pyridine-2-carboxylate [corrected], respectively, by spectroscopic analyses. These compounds showed inhibitory activities for lipopolysaccharide-induced production of interleukin-1beta and tumor necrosis factor-alpha in human whole blood with IC50 values of the range from 0.059 to 2.6 microM.

Agaricales↗
PubMed2001

RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum.

The retinoblastoma protein interacting zinc finger (RIZ) gene is a candidate tumor suppressor gene on 1p36, a region frequently rearranged in a wide variety of human tumors. As the RIZ gene harbors several microsatellites within its coding region, it is a candidate for an inactivating mutation in microsatellite instability (MSI) mediated carcinogenesis. In this study, we examined mutations of two poly adenine tracts, A(8) and A(9), within the coding region of the RIZ gene, in MSI-high (MSI-H) primary cancers occurring in the pancreas, stomach, and colorectum. Frameshift mutations were found in one (10%) of 10 pancreatic, four (36%) of 11 gastric, and two (25%) of eight colorectal cancers. These results indicate that mutations of the RIZ gene play an important role in the pathogenesis of some MSI-H cancers.

Colorectal Neoplasms↗
PubMed2001

Carrier-mediated hepatobiliary transport of a novel antifolate, N-[4-[(2,4-dianninopteridine-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]carbonyl-L-homoglutamic acid, in rats.

The hepatic uptake and biliary excretion of a novel methotrexate derivative, N-[4-[(2,4-diamminopteridine-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]carbonyl-L-homoglutamic acid (MX-68), were examined in rats in vitro using isolated hepatocytes and bile canalicular membrane vesicles (CMVs), respectively. The uptake of MX-68 by isolated rat hepatocytes showed a saturable component (Km = 2.15 microM and Vmax = 2.34 pmol/min/mg of protein) and was inhibited by ATP-depletors and anionic compounds such as taurocholate and probenecid. [3H]MX-68 uptake was also inhibited by folate analogs such as methotrexate and 5CH3-tetrahydrofolate, but the effect of these compounds was slightly less than that of unlabeled MX-68. On replacing Na+ with choline, MX-68 uptake remained unchanged, whereas the methotrexate uptake was reduced. Uptake of MX-68 increased as the extracellular pH fell from 7.5 to 5.5. These results suggest that MX-68 is taken up via active transport systems. The uptake of MX-68 by CMVs prepared from normal rats exhibited clear ATP dependence, whereas ATP had only a minimal effect on the uptake by CMVs from Eisai-hyperbilirubinemic rats with a hereditary deficiency in canalicular multispecific organic anion transporter (cMOAT). The initial uptake rate of ATP-dependent MX-68 transport showed saturation with kinetic parameters similar to those of methotrexate. MX-68 inhibited the ATP-dependent transport of 2,4-dinitrophenyl-S-glutathione, a typical substrate for cMOAT, the inhibition constant (162 microM) being comparable with the Km of ATP-dependent MX-68 transport. These results suggest that the biliary excretion of MX-68 via the bile canalicular membrane is mediated mainly by cMOAT. In conclusion, active transport systems are involved in membrane penetration of MX-68 both at sinusoidal and canalicular sides in the liver, the latter being mainly involved with methotrexate (MTX) whereas the former differs partially from that for MTX.

2-Aminoadipic Acid↗
PubMed2001

Inhibition of biliary excretion of methotrexate by probenecid in rats: quantitative prediction of interaction from in vitro data.

This study was designed to establish a strategy to predict drug interactions involving biliary excretion. The interaction between methotrexate and probenecid was examined as an interaction model since this interaction has already been clinically reported. Coadministration of probenecid reduced the biliary clearance of methotrexate in a dose-dependent manner in rats. This inhibition by probenecid was confirmed in vivo both in the uptake and excretion processes of methotrexate across sinusoidal and canalicular membranes, respectively. That is, both hepatic uptake clearance, assessed in integration plot analysis, and steady-state biliary clearance defined with respect to hepatic unbound methotrexate, were reduced in the presence of probenecid. Probenecid inhibited the active transport of methotrexate both in isolated hepatocytes and canalicular membrane vesicles, confirming the interaction at those two membranes. The degree of inhibition of the uptake and excretion processes found in vivo was comparable with the predicted values using the inhibition constant assessed in isolated hepatocytes and canalicular membranes, respectively. This suggests that the interaction at each membrane transport process can be quantitatively estimated from in vitro data. We have also proposed the method to predict the degree of inhibition of the net excretion from circulating plasma into the bile, the predicted values being also comparable with the inhibition actually found in vivo. The present analysis demonstrates a strategic rationale for predicting drug interactions involving biliary excretion using in vitro systems to avoid any false negative predictions.

Animals↗
PubMed2001

Diagnostic validity of computed tomography for mediastinitis after cardiac surgery.

BACKGROUND: Optimal treatment based on appropriate early diagnosis is essential in managing mediastinitis after cardiac surgery. We evaluated the accuracy of thoracic computerised tomography (CT) in the diagnosis of mediastinitis. METHODS: Forty-one patients in whom we performed CT after cardiac surgery were classified into two groups as follows; Six cases had mediastinitis requiring a redo surgical intervention (Group M). Thirty-five cases recovered without mediastinitis (Group C). Comparisons of CT findings in both groups were made retrospectively. RESULTS: In group M, CT and re-operations were performed 6.3+/-2.5 days and 8.0+/-5.2 days after previous operation, respectively. All but one of redo surgical procedures were mediastinal lavage and omental transplantation. Two patients died due to septic shock and multiple organ failure. CT in group M showed a soft tissue mass with contrast enhancement in 4 patients, bilateral pleural effusion in 5, free gas appearance in 4, and sternal dehiscence or destruction in 2 patients. Consequently, we regarded 4 of the 6 patients in this group as showing postoperative mediastinitis radiographically. In group C, CT performed 16.6+/-7.1 days after operations revealed findings suggestive of mediastinitis in 6 patients. Therefore, in terms of the validity of CT for the diagnosis of mediastinitis, the sensitivity was 67% and the specificity was 83%. CONCLUSION: The sensitivity of CT for diagnosis of mediastinitis after cardiac operations is unsatisfactory. Diagnosis by seeking infective changes in a multidisciplinary way is important in dealing with mediastinitis.

Aged↗