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Biomedical subjects

H Ochiai

Publications and source records attributed to H Ochiai.

At least 91 records · Page 5Linked to original sources

Pancreatic damage resulting from temporary portal triad interruption during partial hepatectomy: protective effect of a prostaglandin I2 analogue.

BACKGROUND: Hyperamylasemia often occurs after hepatectomy, but the detailed mechanism of this phenomenon remains unclear. This study was designed to examine the influence on the pancreas and other organs of temporary portal triad interruption during hepatectomy and to evaluate the protective effect of a prostaglandin I2 analogue. METHODS: Sprague-Dawley rats were intravenously administered normal saline (NS group) or a prostaglandin I2 analogue (PG group) and underwent 70% hepatectomy with temporary portal triad interruption. The 7-day survival rate and the levels of plasma liver enzymes, portal pancreatic enzymes, and endotoxin were determined. Intestinal permeability was evaluated from the portal blood concentration of fluorescein isothiocyanate-labeled dextran administered into the small intestine. The liver, pancreas, small intestine, and lung were examined histologically. Apoptosis in the pancreas was observed by the terminal transferase-mediated dUTP-biotin nick end labeling method. RESULTS: The survival rate of the NS group was 50%, whereas that of the PG group was significantly higher at 100% (P < 0.05). Plasma liver enzymes increased in both groups and showed no significant difference. Portal amylase and lipase levels were significantly lower in the PG group than in the NS group at 12 and 24 h after hepatectomy. Tissue damage in the pancreas and other organs was observed histologically along with the elevation of pancreatic enzymes. Although there were no significant differences between the two groups on hematoxylin and eosin staining, apoptotic acinar cells were only seen in the NS group. The portal endotoxin level (at 3 and 6 h after hepatectomy) and small intestinal permeability (at 1 and 3 h after hepatectomy) were significantly lower in the PG group compared to the NS group. CONCLUSIONS: Temporary portal triad interruption induced hyperamylasemia, congestive damage to the pancreas, and portal endotoxemia due to increased small intestinal permeability. A prostaglandin I2 analogue was able to protect the pancreas and small intestine from such damage.

Alanine Transaminase↗

Failure of treatment with interleukin-2 receptor-specific monoclonal antibody in acute coxsackievirus B3 myocarditis in mice.

T cell activation is assumed to play a crucial role in many viral infections. An important marker for the activation of T cells is the interleukin-2 receptor (IL-2R); resting T lymphocytes do not bear detectable amounts of IL-2R. AMT13, a rat monoclonal antibody against mouse IL-2R, inhibits interleukin-2-dependent cell growth both in vitro and in vivo. Therefore, to clarify the effects of anti-IL-2R antibody treatment upon coxsackievirus B3 (CB3)-infected C3H/He mice, AMT13, 1 microg/mouse per day, was administered, subcutaneously, starting on day 0 (group 2) in experiment I or on day 7 (group 4) in Experiment II for 7 days, respectively. Groups 1 and 3 were examined as infected controls. In both experiments, there was no significant difference in mortality or in the severity of myocarditis between the treated and the untreated groups. Also, myocardial CB3 titers on day 7 did not differ significantly between groups 1 and 2. In addition, the distribution of activated T cell subsets in the inflamed myocardium was not changed by the treatment, and the paucity of myocardial IL-2R-positive cells was confirmed in all groups. Effects of the antibody treatment were confirmed by a decrease in delayed type hypersensitivity. Although some reports have shown that anti-IL-2R antibody has been successfully applied to ameliorate acute renal graft-versus-host disease, to enhance survival of skin allografts, and to suppress diabetic insulitis, it did not exert a beneficial effect on acute CB3 myocarditis in mice.

Animals↗

Effects of levamisole, an immunomodulator, upon murine encephalomyocarditis virus myocarditis.

To test the therapeutic efficacy of levamisole, 5-week-old DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units of encephalo-myocarditis virus. Levamisole (2.5 mg/kg/per day) was administered intraperitoneally daily, starting simultaneously with the virus inoculation, in experiment I for 14 days, and daily on days 14 to 28 in experiment II in mice that survived to 14 days after virus inoculation. In experiment I, survival was higher, the severity of myocarditis was less, and myocardial virus titers were lower in treated than in untreated animals. In experiment II, levamisole was not effective. No significant changes in serum neutralizing antibody titers occurred in either experiment. Furthermore, levamisole prevented associated lymphoid organ atrophy induced by the virus infection. An additional in vitro study revealed the absence of anti-viral activity of the drug. Thus, levamisole may have favorable effects upon encephalomyocarditis virus myocarditis by preventing the virus-induced lymphoid organ atrophy and reducing myocardial virus replication in the acute stage.

Adjuvants, Immunologic↗

Direct hepatic vein anastomosis during hepatectomy for colorectal liver metastases.

BACKGROUND: When the right and middle hepatic veins (RHV and MHV) and all the short hepatic veins are removed during resection of segments (S) 7 and 8 and part of S 5 and 6 including the caudate lobe, the remainder of S 5 and 6 shows congestion, so restoration of liver function may be delayed. METHODS: In 5 patients with hepatic metastases of colorectal carcinoma, which were in the region circumscribed by the RHV, MHV, and inferior vena cava, direct hepatic vein anastomosis was performed during hepatectomy. RESULTS: Hepatic vein reconstruction took 17 to 30 minutes to complete. All 5 patients had an uneventful postoperative course, and the anastomosis was patent at 1 month after operation. One patient died of recurrent carcinoma 6 months after operation. Four have remained alive and disease free for 12, 24, 40, and 61 months. CONCLUSION: Direct hepatic vein anastomosis is an option, which should be adopted in hepatectomy, especially in patients with carcinoma invading the major hepatic veins and short hepatic veins.

Aged↗

Cardiac and hemodynamic effects of TZC-5665, a novel pyridazinone derivative, and its metabolite in humans and dogs.

1. TZC-5665 is a novel pyridazinone derivative with vasodilatory and beta-adrenergic blocking activities and type III phosphodiesterase inhibitory action. 2. In healthy volunteers, TZC-5665 was rapidly absorbed and immediately metabolized. Its main metabolite, M-2, remained at a higher concentration in plasma. Orally administered TZC-5665 reduced end-diastolic left ventricular volume (20.16 ml) and exhibited a tendency to increase ejection fraction (0.04). 3. In dogs, M-2 dose-dependently increased cardiac contractility and reduced both preload and afterload. These effects appeared more potent in the failed heart than in the normal heart. At the same dose (30 micrograms/kg), the effects of M-2 seem to be more potent than those of milrinone. 4. We concluded that TZC-5665 is a useful medication for treating patients with chronic congestive heart failure (CHF) because of the positive inotropic and vasodilating effects due to its active metabolite in addition to its own beta-adrenergic blocking actions.

Adult↗

K(+)-Cl- cotransport and volume regulation in the light and the dense fraction of high-K+ dog red blood cells.

We examined a chloride (Cl-)-dependent K+ transport (K(+)-Cl- cotransport) and regulatory volume decrease in dog red blood cells with high K+, low Na+, and high glutathione (GSH) content (HK/HG) due to the presence of an Na(+)-K+ pump. The HK/HG cells were separated according to their density, and the age-marker enzyme activities, such as glucose-6-phosphate dehydrogenase and cholinesterase, were determined. Unexpectedly, we found that young cells were heavier (more dense) and smaller in size compared with the old cells, which were lighter (less dense) and larger. The K(+)-Cl- cotransport was nearly 10-fold higher in the most dense cells, representing a 12% fraction of the total population compared with the lightest cohort. Although K(+)-Cl- cotransport in both the dense and the light cells was activated by N-ethylmaleimide, swelling and depletion of cellular divalent cations and the activation of the transport in the dense cells was greater. Both the dense and light cells regulated their volume when they were isosmotically swollen. Therefore, the lower activity of K(+)-Cl- cotransport might not explain the relative large volume in old HK/HG cells. The concentration of GSH and glutamate was higher in the light cells. Thus the higher the GSH and glutamate concentration, the greater the cell volume and the lower the K(+)-Cl- cotransport.

Acetylcholinesterase↗

Enhanced interleukin-8 production by cultured Chang liver cells subjected to ethanol exposure and subsequent stimulation with tumor necrosis factor-alpha.

We investigated the production of interleukin-8 (IL-8) and chemotactic activity released from Chang liver cells subjected to long-term treatment with ethanol (Et) and subsequent stimulation with tumor necrosis factor-alpha (TNF-alpha). Chang liver cells were cultured in the presence of 5, 50 or 100 mmol/l Et for 4 weeks and then treated with recombinant TNF-alpha (1, 10, 100 U/ml). The culture supernatants were assayed for IL-8 using a sandwich ELISA and chemotactic activity was measured using a chemotactic chamber. Total RNA was also extracted from these cells and IL-8 mRNA was assayed by RT-PCR. In addition, TNF-receptor expression on the Et-treated cells was analyzed by flow cytometry. IL-8 levels in supernatants of cells stimulated with 100 U/ml of TNF-alpha for 48 h rose significantly with increasing concentrations of Et and values obtained were as follows: 4,918 +/- 244.4 pg/ml at 0 mmol/l Et, 5,335 +/- 266.2 pg/ml at 5 mmol/l Et, 8,726 +/- 873.4 pg/ml at 50 mmol/l Et and 9,134 +/- 866.0 pg/ml at 100 mmol/l Et. The chemotactic activity also increased with increasing concentrations of Et and was almost completely suppressed by anti-IL-8 antibody. Using semiquantitative analysis of radioactivity of IL-8 mRNA using a 32P gamma ATP-labeled primer for IL-8 mRNA, Et-treated cells were shown to have markedly higher levels of radioactivity than untreated cells. In addition, TNF-receptor expression was significantly higher in cells treated with 100 mmol/l Et. These data suggest that long-term Et treatment of Chang liver cells stimulated with TNF-alpha may enhance transcription of the IL-8 gene with up-regulation of the TNF receptor.

Antibodies↗

Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese.

To clarify the role of genetic factors in atherosclerotic plaque formation in the carotid artery and magnetic resonance imaging abnormalities in the brain, we investigated the association of these abnormalities with the angiotensin-converting enzyme (ACE) genotype. One hundred sixty-nine subjects (age, 59.2+/-0.8 years, mean+/-SE) admitted to our hospital for health checkups underwent brain magnetic resonance imaging to evaluate lacunar infarction. B-mode ultrasound examinations of the carotid arteries were performed to detect atherosclerotic plaque. The I/D polymorphism of the ACE gene was determined by the polymerase chain reaction method. Multivariate regression analysis was performed to assess the effects of the following variables on the presence of plaque, mean plaque thickness, and number of plaques: fibrinogen, sex, age, body mass index, mean blood pressure, glycosylated hemoglobin, LDL cholesterol, HDL cholesterol, hematocrit, and the D allele of the ACE gene. The frequency of carotid atherosclerotic plaque was significantly (P=.034) higher in subjects with the D allele than in those without this allele. However, the frequency of lacunar stroke was similar in these groups. A multivariate regression analysis showed that the presence of plaque was independently associated with the D allele (odds ratio=3.27, P=.016). However, mean plaque thickness and the number of plaques were not associated with the D allele. The D allele of the ACE gene may be involved in the presence of carotid plaque but not in the extent of this plaque or asymptomatic lacunar stroke in Japanese subjects.

Aged↗

Angiotensin-converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers.

To investigate the relation between the angiotensin-converting enzyme (ACE) gene polymorphism and acute coronary syndromes with respect to environmental factors, we analyzed the association of genotype with the coronary angiographic findings of patients with acute myocardial infarction or unstable angina pectoris, and we examined the linkage of each genotype with established risk factors for coronary artery disease. We determined the ACE genotype in 152 Japanese patients with acute coronary syndromes and 399 healthy individuals. The genotype distributions were not different between the two groups (P=.74, chi2 test). In the former group, coronary angiograms were evaluated by criteria based on the number of diseased vessels, the number of stenotic lesions (> or = 50%), and the relative abnormal arterial portion (extent index). Although the number of stenotic lesions was higher in patients with the DD genotype than in those with the ID or II genotype (P=.006), there were no differences in the number of diseased vessels or the extent index. When only smokers were analyzed, the number of diseased vessels (P=.032), number of stenotic lesions (P=.003), and extent index (P=.019) were all higher in patients with the DD genotype than in those with the ID or II genotype. In contrast, these differences in the respective parameters did not exist in nonsmokers. The results indicate smoking-associated effects of the ACE genotype on the severity of coronary atherosclerosis.

Coronary Artery Disease↗

Tissue angiotensinogen gene expression induced by lipopolysaccharide in hypertensive rats.

There is now convincing evidence that various tissues express their own tissue renin-angiotensin system, which may be regulated independently of the systemic renin-angiotensin system. However, little information is available on the regulation of the tissue renin-angiotensin system. We investigated the regulation of tissue angiotensinogen gene expression with respect to the development of hypertension. We measured basal and lipopolysaccharide-stimulated plasma angiotensinogen concentrations by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 and 13 weeks of age. Basal plasma angiotensinogen concentration in SHR was comparable to that in WKY at 4 weeks of age and was significantly higher than that in WKY at 13 weeks of age. Lipopolysaccharide induced a significant increase in plasma angiotensinogen concentration in both WKY and SHR at 4 and 13 weeks of age. At 4 weeks of age, the basal levels of angiotensinogen mRNA in the liver, fat, adrenal, and aorta were higher in WKY than in SHR. At 13 weeks of age, the basal levels of angiotensinogen mRNA in the fat, adrenal, aorta, spleen, and kidney were higher in WKY than in SHR, while that in the liver did not differ significantly between the two strains. At 4 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, fat, adrenal, and aorta in both WKY and SHR. At 13 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, aorta, and adrenal; decreased those in the spleen; and had no effect in the kidney in both WKY and SHR. Interestingly, lipopolysaccharide increased the angiotensinogen mRNA level in fat only in SHR, with no effect in WKY, at 13 weeks of age. Lipopolysaccharide stimulated tumor necrosis factor-a mRNA expression in fat of WKY and SHR, and the increase in tumor necrosis factor-alpha mRNA level in SHR was significantly greater than that in WKY. Therefore, the increased tumor necrosis factor-alpha mRNA expression may be involved in the increased lipopolysaccharide-induced expression of angiotensinogen gene in fat of SHR at 13 weeks of age. These data suggest that the transcriptional and probably posttranscriptional regulation of angiotensinogen mRNA differs between SHR and WKY, that the regulation of angiotensinogen gene expression is tissue-specific, and that the altered expression of the angiotensinogen gene may be involved in the development of hypertension.

Angiotensinogen↗

Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene.

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

Angiotensinogen↗

Incidence of dogs possessing red blood cells with high K in Japan and East Asia.

The phenotype of high K (HK) red blood cells, which is an autosomal recessive, was found in dog groups from 10 of 13 breeds or populations in Japan. The incidence of HK was 26 to 38% in the San'in-Shiba, Shinshu-Shiba and Akita breeds, and the gene frequencies of HK ranged from 0.513 to 0.612. The highest incidence (42%) was found in the Jindo breed from Korea, and the gene frequency was 0.652. Two other groups from Korea also possessed this HK variation. However, although HK cells were not found in dogs from Taiwan, Indonesia, Mongolia and Sakhalin, Russia, the HK phenotype is clearly distributed now throughout Japan and Korea.

Animals↗

Assessment of the accuracy of indirect blood pressure measurements.

This study assessed the accuracy of indirect blood pressure (BP) measurements by simultaneously performing three kinds of indirect BP measurement on the left arm (auscultatory, microphone and oscillometric methods) and a direct BP measurement on the left arm. The subjects were 34 hospitalized patients, ranging in age from 18 to 73 years (average 47.5 years). Highly significant correlations in systolic or diastolic BP between a given pair of the three indirect methods. The indirect methods underestimated systolic BP and overestimated diastolic BP compared with the direct method, with differences of -12.2 +/- 10.5/+4.6 +/- 7.6 (systolic/diastolic BP) with the oscillometric method, -8.1 +/- 9.7/+1.2 +/- 8.9 with the microphone method and -10.6 +/- 8.1/+3.7 +/- 6.5 mmHg with the auscultatory method. The difference in systolic BP between the auscultatory and direct methods was greater and the difference in diastolic BP was smaller in subjects older than 50 years than in those aged 50 years or less (p < 0.001 for systolic BP, p < 0.05 for diastolic BP). The auscultatory method revealed greater systolic BP in subjects with increased carotid arterial wall stiffness assessed by echoarteriography. Thus, it is concluded that there are inherent differences in BP between the indirect and direct methods which can be attributed to the changes in arterial wall physical properties partly due to aging.

Adolescent↗

Heredity of red blood cells with high K and low glutathione (HK/LG) and high K and high glutathione (HK/HG) in a family of Japanese Shiba Dogs.

Forty-two of 81 dogs from a family of Japanese Shiba dogs had red blood cells with a high K and a low Na concentration (HK). Of the HK dogs, 32 were high K and low glutathione (HK/LG) and 10 were high K and high glutathione (HK/HG). These variants were found in both males and females. The phenotype of HK was inherited in a recessive mode as reported earlier. A high incidence of HK/LG dogs was found in this family, and the phenotype was also inherited in a recessive mode. Glutamate (Glu) influx, which defines the cellular glutathione concentration, was lower in HK/LG cells than in HK/HG cells (in some cases extremely low). The fact that the red blood cells of HK/LG dogs have the two varying characteristics of a remaining Na, K-pump and low Glu transport suggests that 2 or more genes may be involved. Since an extremely low Glu influx was also found in normal low K and high Na (LK) red blood cells, the characteristic of low Glu transport also exists in LK cells. The phenotype of low Glu transport may also be inherited in a recessive mode. This family therefore had a very high incidence of homozygous recessive genes which control the phenotypes for the Na, K-pump and low Glu transport.

Animals↗

Torsades de pointes complicating pentamidine therapy of Pneumocystis carinii pneumonia in acute myelogenous leukemia.

Pentamidine isethionate induced torsades de pointes in a 33-year-old woman with acute myelogenous leukemia. This is the first report of Pentamidine-induced torsades de pointes in Japan for over ten years. On the 4th day of intravenous pentamidine for Pneumocystis carinii pneumonia, asymptomatic sinus bradycardia was noted with QT interval prolongation, and torsades de pointes were revealed on the 8th day. Although torsades de pointes was dissolved with discontinuation of the intravenous pentamidine and administration of magnesium sulfate, sinus bradycardia and prolonged QT interval persisted. Ventricular pacing resulted in no arrhythmia and normalization of the QT interval on the 10th day after discontinuation of pentamidine. Careful monitoring of the electrocardiogram should be carried out during intravenous pentamidine therapy.

Adult↗

[Brain stem glioma presenting with contralateral sensory impairment of ascending nature].

A case of brain stem glioma, presenting with impairment of contralateral pain-temperature sense of ascending nature, is reported. A 38-year-old woman with documented neurofibromatosis type 1 (NF-1) was admitted to our hospital for treatment, complaining of diminished pain-temperature sense in the left lower extremity. On admission, the symptom was first evaluated to be due to cervical myelopathy although motor involvement was absent. An MRI, myelography and CT-myelography of the cervical spine were done, demonstrating no abnormality. Shortly after the admission the sensory impairment progressed to the upper chest level and then to the upper extremity on the left. Because of her documented NF-1 a brain CT was checked, revealing a small mass with ring enhancement in the dorsal midbrain on the right. On MRI, the tumor location was at the right dorsolateral tectal region of superficial situation. Under the diagnosis of midbrain glioma the tumor was partially removed by the occipital transtentorial approach. At operation, the tumor has grown intraaxially, having pinkish-gray color and central necrosis. Histologically the tumor was diagnosed as glioblastoma multiforme. Postoperatively she presented a definite improvement of the sensory impairment in the reverse order, that is from upper extremity and then to the lower extremity. Progression and post-treatment improvement of the impaired pain-temperature sense in this case suggested that the topography and lamination of the lateral spinothalamic tract might be present even in the dorsal midbrain, namely the posterior-superficial layer to be sacral segment and the anterior-deep layer to be cervical one.

Adult↗

[Assessment of auscultatory blood pressure measurements versus intra-arterial pressure in patients with atrial fibrillation].

The accuracy of auscultatory blood pressure (BP) determination was assessed in patients with chronic atrial fibrillation by performing simultaneous auscultatory BP determination on the upper arm and a direct BP determination on the contralateral arm. The subjects were three hospitalized patients, aged from 52 to 75 years. A Teflon catheter was introduced into the radial artery which was connected to a pressure transducer, and a cuff was twisted around the contralateral upper arm in the supine position. Simultaneous recording of directly determined BP and cuff pressure enabled the comparison of direct BP with auscultatory BP. The appearance of the Korotkoff I sound (systolic BP) and V sound (diastolic BP) was marked on the cuff pressure curve. This maneuver was repeated five times in each patient. The method of Bland and Altman was employed to assess the agreement between auscultatory and direct determinations. The auscultatory method estimated BP with differences of -14.3 to +27.3 mmHg in systolic BP and -12.1 to +11.9 mmHg (+/-2SD) in diastolic BP compared with the direct method. The difference in systolic BP between the auscultatory and the direct methods was greater than that in diastolic BP. Thus, there are unacceptable differences in systolic BP between auscultatory and direct methods that can be attributed to BP fluctuations. The auscultatory method in diastolic BP is more accurate than that in systolic BP and may be more useful in the clinical setting.

Aged↗

Contribution of tumor necrosis factor alpha and interleukin-1 alpha on the production of macrophage inflammatory protein-2 in response to respiratory syncytial virus infection in a murine macrophage cell line, RAW264.7.

The production of several inflammatory cytokines, such as murine macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor (TNF), and interleukin (IL)-1, was investigated in response to respiratory syncytial virus (RSV) infection in a murine macrophage cell line, RAW264.7, with special reference to mutual relation of their productions. The kinetics of MIP-2 production showed a trend for a biphasic pattern, that is, MIP-2 levels became detectable from 2 h postinfection (p.i.) and increased markedly until 8 h p.i. Thereafter, this level fell to the same level until 16 h p.i. and then increased again. TNF alpha was also detectable at 2 h p.i. and then increased sharply until 8 h p.i., when the peak level attained. Compared with the levels of MIP-2 and TNF alpha, that of IL-1 alpha/beta, especially IL-1 beta, was lower (ng versus pg/ml order). The presence of anti-TNF alpha or anti-IL-1 alpha antibody did not influence the early phase of MIP-2 production but significantly inhibited the late phase, suggesting that MIP-2 is induced by the combined effects of RSV infection via direct induction and indirectly after initial induction of TNF alpha and IL-1 alpha productions. Although RSV-infected RAW264.7 cells had no alteration in viability compared with mock-infected control, these data demonstrate that RSV is a potent inducer of inflammatory cytokines by direct induction and indirectly via the initial production of other cytokines.

Animals↗