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Biomedical subjects

R Hirai

Publications and source records attributed to R Hirai.

At least 19 recordsLinked to original sources
PubMed2001

Superior mesenteric artery syndrome in identical twin brothers.

We report two identical male twins who suffered from superior mesenteric artery (SMA) syndrome. A 28-year-old man was admitted for investigation of postprandial nausea and vomiting. Upper gastrointestinal examination revealed a dilated proximal duodenum with an abrupt vertical cutoff of barium flow in the third portion of the duodenum, establishing the diagnosis of SMA syndrome. One year later, his twin brother also presented similar symptoms and was radiologically diagnosed as SMA syndrome. The twin brothers did not respond adequately to conservative therapy and underwent duodenojejunostomy. This is the first report of SMA syndrome in identical twins.

Adult↗
PubMed2001

Microsatellite instability correlates with normal expression of cyclin E in hepatocellular carcinomas.

It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.

Aged↗
PubMed2000

Establishment of a human hepatoma cell line, HLE/2E1, suitable for detection of p450 2E1-related cytotoxicity.

By transfection of an expression vector of human cytochrome P450 2E1 (CYP2E1) into a human hepatoma cell line (HLE), a new cell line (HLE/2E1) that stably expresses activity of CYP2E1 has been established. The HLE/2E1 cell line expressed a higher level of CYP2E1 messenger ribonucleic acid than did the mother HLE cell line. CYP2E1 enzyme activity determined by a p-nitrophenol oxidation assay was also higher in HLE/2E1 cells than in HLE cells. In addition, the enzyme activity of the HLE/2E1 cells was increased by ethanol treatment. Exposure to acetaminophen (APAP) or buthionine sulfoximine (BSO) caused a greater decrease in viability of the HLE/2E1 cells than that of the HLE cells, as determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The cytotoxicity of APAP or BSO to HLE/2EI cells was inhibited by the addition of ethanol or vitamin E. However, the cytotoxicity of both APAP and BSO was enhanced by 24-h preincubation of HLE/2E1 cells with ethanol. These results show that this cell line provides a useful model for studying catalytic properties of CYP2E1 and cytotoxic mechanisms of chemicals metabolized by CYP2E1.

Acetaminophen↗
PubMed2000

Efficacy of adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device in adults with acute severe asthma.

BACKGROUND: The efficacy of combination therapy adding multiple doses of anticholinergics to beta(2)-agonists to improve outcome has not been established in adults with acute severe asthma. OBJECTIVE: This study was undertaken to compare the outcome of adults with acute severe asthma treated with 4 puffs of salbutamol (100 microg/actuation) every 20 minutes for 3 doses plus 4 puffs of oxitropium bromide (100 microg/actuation) with each of the 3 salbutamol doses versus salbutamol alone administered by means of a metered-dose inhaler with a spacer device. METHODS: A randomized, single-blind, placebo-controlled study was performed in 74 patients between 18 and 55 years old presenting to the emergency department (ED) for treatment of acute asthma with a peak expiratory flow (PEF) of 50% or less than the normal predicted value. The primary endpoint was improvement in PEF over the course. The secondary endpoint was the need for additional ED treatment at 120 minutes. RESULTS: The increase in PEF over the course was significantly greater in the oxitropium plus salbutamol treatment group (P <.0001). The mean absolute difference in PEF at 120 minutes for combination therapy compared with salbutamol alone was 37.8 L/min (P =.001). In addition, the proportion of need for additional ED treatment was less in the combination group than the group receiving salbutamol alone (odds ratio, 0.32; 95% confidence interval, 0.11-0.90). CONCLUSION: Adding multiple doses of oxitropium bromide to salbutamol delivered by means of a metered-dose inhaler with a spacer device for acute severe asthma produces a significant improvement in lung function and reduces the need for additional ED treatment.

Acute Disease↗
PubMed2000

Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats.

Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.

Animals↗
PubMed1999

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver.

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6). Saline water was administered in the same way in the control group (n = 6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function after warm ischemia of porcine liver.

Analysis of Variance↗
PubMed1997

Endothelin-1 levels in portal venous blood in relation to hepatic tissue microcirculation disturbance and hepatic cell injury after ischemia/reperfusion.

This study was conducted to clarify the role of endothelin-1 in the portal vein after hepatic ischemia/ reperfusion and to ascertain whether it is related to hepatic microcirculation disturbance. Using a canine ischemic liver model, the portal and systemic endothelin-1 levels were measured before ischemia, then after 1 h and 2 h of reperfusion, and comparatively evaluated with the serum levels of GOT and lactic dehydrogenase (LDH). As an indicator of liver tissue microcirculation, tissue blood flow volume (TBF) was also measured in the site subjected to ischemia. The animals were divided into: group 1, which received ischemia for 30 min; group 2, which received ischemia for 60 min; and group 3, which received a sequence repeated four times of 15 min ischemia and 10 min reperfusion. The portal endothelin-1 level became significantly elevated after reperfusion compared to that before ischemia in all groups, being significantly higher in group 2 than in the other groups. The systemic endothelin-1 level also increased after reperfusion; significantly in group 2. The portal endothelin-1 level was generally higher than the systemic level, which again was statistically significant in group 2. After 2 h of reperfusion, a significant positive correlation was found between the portal endothelin-I level and serum LDH, whereas a significant negative correlation was found between the portal endothelin-1 level and TBF. The finding that the portal endothelin-1 level became elevated after hepatic ischemia/reperfusion suggests that it probably plays an essential role in hepatic ischemia/ reperfusion injury by adversely influencing tissue microcirculation.

Animals↗
PubMed1996

A human transforming growth factor-beta type II receptor that contains an insertion in the extracellular domain.

In the signal transduction of transforming growth factor-beta (TGF-beta), the TGF-beta type II receptor (betaR-II) binds TGF-beta, presents the ligand to type I receptor, and forms a heterodimeric receptor complex that functions as an active signaling receptor. We isolated cDNA clones encoding an isoform of human betaR-II from vascular endothelial cells by RT-PCR. The deduced structure of the isoform designated as betaR-IIb contained a 25-amino-acid residue inserted at the extracellular region. The insert exhibited 73% homology to a similar insertion found in a mouse betaR-II variant. BetaR-IIb mRNA was ubiquitously expressed in all human cell lines examined. BetaR-IIb as well as betaR-II stably expressed in betaR-II deficient DR26 cells acted as a functional receptor transducing signals from TGF-beta for growth inhibition and the transcriptional activation of the plasminogen activator inhibitor-1 promoter. These results indicated that the betaR-IIb expressed in mammalian cells functions indistinguishably from in betaR-II. The potential function of betaR-IIb is discussed.

Amino Acid Sequence↗
PubMed1996

Continuous measurement of tissue oxygen and carbon dioxide gas tensions in dog liver in ischemia/reperfusion.

An experiment was conducted to determine whether the oxygen and carbon dioxide gas tensions in liver tissue (PtO2 and PtCO2, respectively) reflect the state of microcirculation and/or metabolism in the ischemic liver. Subjects were divided into three groups: group 1, 30 min ischemia; group 2, 60 min ischemia; group 3, four times of intermittent 15 min ischemia after every 10 min of reperfusion. PtO2, PtCO2 and tissue blood flow (TBF) were measured by mass spectrometry, comparatively studied with the serum GOT level as an indicator of liver tissue damage. Furthermore, the time point at which the PtCO2 increase for 1 min initially became less than 1/2 of the maximum value was located on the transit curve of PtCO2, referred to as the critically anaerobic (CA) point, with which new indices of critically anaerobic score (CAS) and time (CAT) (see details in text) were developed. The profiles of PtO2 and PtCO2 during ischemia and reperfusion were clearly demonstrated, and the CA point was observed 12.7 +/- 2.9 min after induction of ischemia. PtO2 was positively correlated with TBF and negatively with the serum GOT level. Furthermore, not only CAS but also CAT were significantly correlated with PtO2, TBF, and the serum GOT level. It was concluded that PtCO2 reflects the state of anaerobic tissue metabolism during ischemia and PtO2 reflects the magnitude of microcirculatory disturbance and tissue injury caused by ischemia/reperfusion. Therefore, continuous monitoring of not only PtO2 but also PtCO2 is beneficial for patients undergoing hepatic surgery with ischemia.

Animals↗
PubMed1995

[Suppression of postoperative liver metastases from colon cancer by continuous intraportal infusion of an angiogenesis inhibitor FR-118487].

A rabbit VX2 colon cancer model with spontaneous liver metastases was used to evaluate the antitumor effect of an angiogenesis inhibitor, FR-118487. FR-118487 (1 mg/kg/day) was infused continuously into the portal vein for a week after resection of primary colon cancer lesions (FR group). The incidence of liver metastases was 71.4% (5/7) in FR group, and 100% (7/7) in control group. The number and the weight of liver metastatic nodules were 31.0 +/0 36.0 and 1.4 +/- 1.8 g in FR group versus 83.7 +/- 73.9 and 6.5 +/- 4.9 g in control group, respectively. The metastases in FR group were significantly decreased in weight compared with those in control group (p < 0.05). No anastomotic leakage was recognized in either group. No side effects of FR-118487 such as body weight loss were found. Continuous intraportal infusion of FR-118487 in the early postoperative period may be effective to suppress liver metastases from colon cancer by inhibiting the angiogenesis concerning liver metastases.

Animals↗
PubMed1994

Ultrastructural analysis of tyrosine hydroxylase-, substance P-, and calcitonin gene-related peptide-immunoreactive nerve fibers in the rat iris.

Different patterns of distribution of chemically different nerve fibers in the rat iris were studied by immunoelectron microscopy. The iris was immunostained either singly for tyrosine hydroxylase (TH), or doubly for substance P (SP) and calcitonin gene-related peptide (CGRP), or triply for TH, SP and CGRP. TH-positive fibers were distributed in the stroma near the iris dilator and within the iris sphincter. SP/CGRP-positive fibers were found mainly in the anterior half of the stroma and partly in the stroma close to the sphincter, but were hardly ever seen in the stroma near the dilator or within the sphincter. Fibers neither positive for TH, SP nor CGRP were observed in the stroma near the dilator and within the sphincter.

Animals↗
PubMed1994

[An immunoelectron microscopic study of distribution and density of nerve fibers innervating the rat iris].

We studied the sympathetic, parasympathetic and sensory nerve fibers in the rat iris using electron microscopic immunohistochemical techniques. Antibodies raised against tyrosine hydroxylase (TH), substance P (SP), and calcitonin gene-related peptide (CGRP) were used alone or combined together to characterize the nerve fibers. The ratios of the TH-positive, SP/CGRP-positive and TH/SP/CGRP-negative fibers were 18%, 37%, and 45% in the anterior half of the dilator stroma, 11%, 3%, and 86% in the posterior half of the dilator stroma, 45%, 26%, and 29% in the sphincter stroma, and 23%, 1%, and 76% in the sphincter muscle layer. These results confirm that the sympathetic and parasympathetic fibers doubly innervate both rat iris sphincter and iris dilator muscles, whereas sensory nerve fibers innervate mainly the stroma.

Adrenergic Fibers↗
PubMed1993

Enhancement of T-cell proliferation by PSK.

Protein-bound polysaccharide, PSK, is a biological response modifier and influences various immunological functions in vivo, including those of T-cells. However, PSK has not been proved to stimulate proliferation of T-cells in vitro in contrast to various lines of evidence that indicate the proliferation of B-cells in vitro. PSK enhanced the proliferation of spleen cells in C3H/He and nude mice in vitro. In this study such proliferating cells were detected by monoclonal antibody to bromodeoxyuridine (BrdU) incorporated into DNA, and their subsets were determined by flowcytometry with monoclonal antibody to Thy1 as a cell surface marker of T-cells. When spleen cells from C3H/He mice were cultured with PSK for 3 days, the percentage of BrdU positive cells increased, and about 67% of BrdU positive cells were Thy1.2 positive. In addition, PSK also had the activity to enhance the proliferation in a T-cell-enriched fraction from spleen cells by nylon fiber columns as well as that in original spleen cells. These results suggest that PSK enhances the proliferation of T-cells as well as B-cells.

Adjuvants, Immunologic↗
PubMed1992

Inhibition of different steps of the ubiquitin system by cisplatin and aclarubicin.

Ubiquitin is involved in such fundamental cellular processes as cell cycle control, DNA repair, protein degradation and stress responses. We previously reported that cisplatin could inhibit the ubiquitin-ATP-dependent proteolysis and ubiquitination. We further investigated the effect of various antitumor agents on the ubiquitin system and found that aclarubicin (ACR) inhibits the ubiquitin-ATP-dependent proteolysis but not the ubiquitination process. We found that ACR as well as cisplatin inhibited the ubiquitin-ATP-dependent proteolytic activity of rabbit reticulocytes. The IC50 values of these agents were 52 and 90 microM, respectively. Although cisplatin inhibits the conjugation of ubiquitin to proteins through the inhibition of a ubiquitin-activating enzyme, ACR, at 120 microM, does not. Thus, the antitumor agents affecting the ubiquitin system could be classified into two groups; one is represented by cisplatin, which inhibits the ubiquitination of the proteins, and the other is ACR, which does not inhibit the ubiquitination but does inhibit the ubiquitin-ATP-dependent proteolysis. Mitomycin C belongs to the latter group.

Aclarubicin↗
PubMed1992

Species-specific differences in the mitogenic activity of heparin-binding growth factors in the sera of various mammals.

Sera from different mammalian species displayed great differences in mitogenic activity, as measured by stimulation of DNA synthesis in BALB/c 3T3 cells (3T3 cells). Among the sera examined, fetal bovine serum was least active, and increasing activity was detected in calf serum, human serum, rat serum and mouse serum, in that order. Rat and mouse sera exhibited extremely high mitogenic activity with 3T3 cells, but when TIG-1 human fetal lung fibroblasts were used for the DNA assay instead, the activity levels of all of the sera were lower, and the differences between them were smaller. To determine the reasons for these differences, the heparin-binding growth factors in each serum were separated on a heparin affinity column. Five peaks of DNA-stimulating activity were obtained. Three of these were found in all sera examined, with both 3T3 cells and TIG-1 cells. Two other peaks were found only with 3T3 cells; one was peculiar to rat and mouse sera, with extremely high activity in the rat, and the other was specific to fetal serum. The dependence of the activity of these peaks on the cells used for the test was confirmed using normal rat lung fibroblasts and immortalized rat kidney cells. These findings adequately explain the species-specific differences in mitogenic activity of whole sera, and the variation in activity depending on the cells used for assay of DNA synthesis.

3T3 Cells↗