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Biomedical subjects

H Hiraoka

Publications and source records attributed to H Hiraoka.

At least 19 recordsLinked to original sources

Enhanced expression of rat obese (ob) gene in adipose tissues of ventromedial hypothalamus (VMH)-lesioned rats.

A responsible gene of genetically obese (ob/ob) mouse has recently been isolated. Genetic disruption of ob gene causes massive obesity. To elucidate the pathophysiological regulation of ob gene, we examined the gene expression in fat tissues of a non-genetical obese model, VMH-lesioned rats. The ob mRNA was identified in both subcutaneous and mesenteric fat tissues in the control rats. In VMH-lesioned rats, the abundance of ob mRNA increased after the gain of body weight and marked expression was observed on 15th day after making VMH lesion. These data suggest that ob gene might be up-regulated with fat accumulation even in non-genetically obese animals.

Adipose Tissue

Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator.

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor from the producing cells, and normally remains in this form associated with the extracellular matrix. In response to tissue injury, the single-chain precursor is converted to a biologically active heterodimer by a serine protease, the activity of which is induced in the injured tissue. We have previously identified HGF activator, a serum serine protease that activates single-chain HGF. The sequence of HGF activator cDNA revealed that the HGF activator is homologous to blood-coagulation factor XIIa. In this study, we found that coagulation factor XIIa has an ability to activate single-chain HGF. Factor XIIa exhibited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was slightly lower than that of the HGF activator. Since factor XIIa is activated during the initiation of contact activation induced by tissue injury, factor XIIa may function as an HGF-converting enzyme together with HGF activator in the injured tissue. C1-inhibitor, antithrombin III and alpha 2-antiplasmin, that regulate the blood-clotting activity of factor XIIa, were also effective against the HGF-converting activity of factor XIIa. Furthermore, factor XIIa was not active in the HGF-converting activity in serum. Thus, the HGF-converting activity of factor XIIa may be regulated by these serum inhibitors.

Factor XIIa

Klippel-Trenaunay syndrome associated with splenomegaly: report of a case.

We report herein the case of a 19-year-old woman, diagnosed as having Klippel-Trenaunay syndrome at the age of 3 years, who presented to our hospital with severe abdominal pain. Abdominal computed tomography revealed splenomegaly, ascites, and paracentesis confirming an intraabdominal hemorrhage. Thus, an emergency laparatomy was performed for a suspected splenic rupture, and 2.5 L of blood was drained from the abdominal cavity. Splenomegaly was confirmed, and a splenectomy was performed. The patient's postoperative course was complicated by disseminated intravascular coagulation, but she recovered and was discharged 3 weeks following surgery. Pathological examination of the spleen suggested that the splenomegaly was caused by high venous pressure due to splenic vein stenosis. To our knowledge, this is the first reported case of Klippel-Trenaunay syndrome associated with marked splenomegaly.

Adult

Large and cholesteryl ester-rich high-density lipoproteins in cholesteryl ester transfer protein (CETP) deficiency can not protect macrophages from cholesterol accumulation induced by acetylated low-density lipoproteins.

High-density lipoprotein (HDL) has been speculated to have an anti-atherogenic function. Many in vitro studies have demonstrated that HDL has the ability to remove cholesteryl ester (CE) from lipid-laden macrophages. However, the effect of alteration in chemical composition and particle diameter on the in vivo function of HDL is unknown. In the study described here, we have isolated the HDL from patients homozygous for cholesteryl ester transfer protein (CETP) deficiency and examined its function in vitro, in order to clarify the anti-atherogenic property of HDL in CETP-deficient subjects. Apolipoprotein (apo) E-free HDL2 from the patients, separated by heparin-Sepharose column chromatography, was rich in CE, poor in triglycerides (TG), and enlarged in size on 4-30% nondenaturing polyacrylamide gradient gel electrophoresis. In contrast, HDL3 from the patients was normal in size and in its chemical composition. First, we examined the effect of HDL on CE accumulation in macrophages. After mouse peritoneal macrophages had been incubated with both acetylated low-density lipoproteins (Ac-LDL) and HDL, cellular CE content was determined by an enzymatic, fluorometric method. Ac-LDL alone induced a 9-fold accumulation of CE. The addition of apo E-free HDL2 and HDL3 from controls and patients' HDL3 prevented CE accumulation in macrophages, while patients' HDL2 had no preventive effect. We next investigated the in vitro ability of HDL to remove cellular CE from lipid-laden macrophages after incubation with Ac-LDL. After loading of macrophages with cholesterol by Ac-LDL, HDL was added to the culture medium and the cellular CE content was measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents

Low-density lipoproteins in hyperalphalipoproteinemic heavy alcohol drinkers have reduced affinity for the low-density lipoprotein receptor.

Heavy alcohol intake causes a marked inhibition of cholesteryl ester transfer protein (CETP) activity resulting in cholesterol ester enrichment of HDL. In this study we have characterized LDL of 35 chronic heavy alcohol drinkers with hyperalphalipoproteinemia to clarify the effect of alcohol on the metabolism of LDL. Serum concentrations of LDL-cholesterol and apolipoprotein B were normal, while the chemical composition of LDL was characterized by depletion of cholesteryl ester and enrichment of triglyceride. The LDL particles of the drinkers were significantly smaller in size than those of controls and had reduced affinity for LDL receptors of normal human fibroblasts. After cessation of alcohol, these abnormal characteristics returned toward normal along with elevation of CETP activity. These results suggest that heavy alcohol intake alters the compositions and particle size of LDL, consequently reducing their affinity for LDL receptors. This may be attributed, at least in part, to the reduction of CETP activity.

Adult

Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity.

Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% +/- 4.2%/10 microL/18 h in alcohol drinkers v 20.5% +/- 2.4%/10 microL/18 h in control; mean +/- SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (< 25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Plasmid transformation in Bacillus subtilis NB22, an antifungal-antibiotic iturin producer.

A transformation system with plasmids was developed for Bacillus subtilis NB22, an antibiotic iturin producing strain. Treatment of B. subtilis NB22 with 4 M KCl was effective for the induction of competence, followed by uptake of plasmid DNA in the presence of polyethylene glycol. The efficiency of transformation of this bacterium with pC194 and pUB110 was 4.1 X 10(3) and 1.5 X 10(3) transformants per micrograms DNA, respectively and the transformation frequency was 3.3 X 10(-3) and 7.2 X 10(-4), transformants per viable cell, respectively. This method was much faster and three orders of magnitude more efficient in transformation efficiency than protoplast transformation methods.

Anti-Bacterial Agents

The effects of hyperthermia on the cell cycle of Ehrlich ascites cancer cells in vivo.

The effects of hyperthermia on the cell cycle of Ehrlich ascites cancer cells were studied, and these effects simultaneously evaluated in terms of prolonging the survival of test mice inoculated with tumor cells from heat-treated mice. DDY mice bearing Ehrlich ascites cancer cells were placed in a water bath at 37 degrees C, 39 degrees C, 41 degrees C, 42 degrees C. The heating of mice at 41 degrees C, 42 degrees C and 43 degrees C induced the accumulation of cancer cells at the G2M phase of the cell cycle with many cells exhibiting polyploidy (16 C). The extent of accumulation increased as the temperature of incubation was raised, however the interrupted cell cycle resumed 120 hours after heating. The retransplantation of cells from the heat-treated mice revealed that the mice which were inoculated with Ehrlich ascites cancer cells from mice heated at 43 degrees C survived longer, while the mice which were inoculated with Ehrlich ascites cancer cells from mice heated at 39 degrees C survived for only a slightly shorter time than those which were inoculated with cells from mice heated at 37 degrees C.

Animals

[Doppler echocardiographic features of the atrial and ventricular filling modes and their significance in restrictive myocardial diseases].

The filling modes into the right atrium and both ventricles were observed using pulsed Doppler echocardiography in six cases of restrictive myocardial diseases, and these were compared with those of 13 cases of constrictive pericarditis, six cases of lone atrial fibrillation and 16 healthy subjects. Special attention was paid to the mechanical properties of the cardiac walls which might be reflected in the filling modes. 1. In the restrictive cases, right atrial filling from the superior caval vein during ventricular systole was reduced in velocity and duration, but the atrial filling during ventricular diastole was not appreciably changed. This flow pattern was similar to that of lone atrial fibrillation, indicating reduced distensibility or impaired contraction and ejection fraction of the right atrium. In constrictive pericarditis, the right atrial filling time was shortened both in ventricular systole and diastole, reflecting stiffening of the pericardium. 2. In the restrictive cases, the first half of the left ventricular rapid filling wave was steep and the skirt of the descending limb was prolonged, while there was no such tendency in the right ventricle. In constrictive pericarditis, the rapid filling time was shortened in the right ventricle, and was not significantly changed in the left ventricle. 3. The differences in the atrial and ventricular filling patterns between restrictive myocardial disease and constrictive pericarditis may serve to distinguish these two disease entities.

Adult

Effects of thermotherapy on the morphology and cell cycle of a transplanted ascites hepatoma in rats.

The effects of heating on the morphology and cell cycle of ascites hepatoma AH-100B cells were investigated. Five rats with AH-100B ascites cells were warmed in a water bath at 39 degrees C, 41 degrees C, or 43 degrees C, respectively. After heating, changes in the morphology of tumor cells were observed every day over a 3-day period under a light microscope and changes in the nuclear DNA content were measured by microspectrophotometry. Morphologic changes in AH-100B cells, which included swelling and vacuolization of the cytoplasm and constriction, vacuolization and destruction of nuclei, were observed. Multinucleated giant cells were characteristically observed in the cells from rats heated to 43 degrees C. In the case of rats heated to 43 degrees C, an increase was seen in the number of cells with a DNA content of 8C to 10C, and some of the cells exhibited polyploidy with a DNA content greater than 10C. It appears that one of the mechanisms of the antitumor effect of hyperthermia in vivo involves changes in the cell cycle of cancer cells and the accumulation of polyploid cells.

Animals

Primary leiomyosarcoma of the inferior vena cava with Budd-Chiari syndrome.

A 44-year-old Japanese woman with leiomyosarcoma of the inferior vena cava is reported. She presented with Budd-Chiari syndrome and died of hepatic failure about 3 months after the onset of symptoms. The tumor arose from the middle segment of the inferior vena cava, occluded the inferior vena cava and projected into the right atrium. A total of 28 cases of Budd-Chiari syndrome due to primary leiomyosarcoma of the inferior vena cava are reviewed.

Adult

[Significance of disturbances of cardiac filling in constrictive pericarditis].

Using pulsed Doppler echocardiography, blood filling patterns of the right atrium and left and right ventricles in constrictive pericarditis were studied to evaluate the physiological role of the pericardium in the hemodynamics of this disease. Thirteen cases were examined including five cases with atrial fibrillation. The control subjects consisted of 16 healthy persons and six cases of lone atrial fibrillation. 1. Peak velocity of the atrial filling wave during ventricular systole was reduced, and the filling time was shortened, suggesting reduced compliance and restricted motion of the atrial wall, because of the thickening and adhesions of the pericardium. Duration of the atrial filling wave during ventricular diastole was also shortened, reflecting disturbance of the early diastolic filling of the right ventricle. 2. In healthy subjects, duration of the rapid filling wave was longer in the right ventricle than in the left ventricle, probably due to the greater compliance of the right ventricular wall as compared to that of the left ventricular wall. In constrictive pericarditis, the rapid filling time of the right ventricle is shortened, so that the difference in this time between the right and left ventricles is minimized, which may be related to a thinner right ventricular wall. Duration of the rapid filling wave of the right ventricle correlated with right ventricular end-diastolic pressure, indicating that the duration of the right ventricular rapid filling wave is proportional to the severity of constrictive pericarditis. In conclusion, constriction of the pericardium definitely influences the hemodynamics of the right side of the heart more than it does the left side in constrictive pericarditis. This difference appears to result from the difference in thickness of the myocardial layers of both ventricles.

Adult

Characterization of a human monoclonal antibody with broad reactivity to malignant tumor cells.

Lymphocytes from mediastinal lymph nodes of 9 patients with primary lung cancer were fused with murine myeloma cells (P3U1). One of the clones (4G12) was stable for secretion (10 micrograms/ml) of human IgM lambda for 24 months. The antigen detected by 4G12 was sensitive to both trypsin and periodic acid-Schiff treatment. It immunoprecipitated a glycoprotein with an Mr of 65,000 upon analysis in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reduced conditions. Immunohistochemical staining demonstrated that 4G12 possessed a high reactivity to squamous cell carcinomas of the lung (29 of 29) and also reacted with other lung carcinomas [adenocarcinomas (14 of 20) and large cell carcinomas (3 of 8)] and with some nonpulmonary malignant tumors (15 of 56). However, it did not react with small cell carcinomas of the lung. No benign tumors (0 of 26) so far tested have been positive. 4G12 did not react with most of the normal tissues; an exception was that it was weakly reactive on the glandular cells of the trachea and bronchi and on the proximal tubular cells of the kidneys. Thus 4G12 showed a broad reactivity to malignant tumors (68% of lung carcinomas, 27% of nonpulmonary carcinomas, and 0% of benign tumors). The reactivity of 4G12 on tissues from squamous cell carcinomas of the lung indicated that the expression of the antigenic determinant was much more in the well-differentiated grade than in the poorly differentiated grade. Thus the antigen detected by 4G12 appears to be related to tumor differentiation. Moreover, fluorescence-activated cell sorter analysis demonstrated that the expression of the antigen epitope depended on the cell cycle (G2-M). These data suggest that the 4G12 monoclonal antibody detects a new tumor-associated antigen that is recognized by the human immune system.

Adenocarcinoma

Malignant pleomorphic adenoma (malignant mixed tumor) of the trachea. Report of a case.

Malignant pleomorphic adenoma arising in the trachea has not been reported in the literature. We report here a case of malignant pleomorphic adenoma (malignant mixed tumor) occurring in the trachea of a 65-year-old woman. The tumor metastasized to the lung and the chest wall 11 years after complete resection of the primary tumor, which was a polypoid submucosal tumor, 1.3 cm in diameter. Light microscopic examination of the primary and metastatic tumors showed the presence of epithelial and stromal elements, consisting of grandular structures, foci of squamous metaplasia and a myxochondroid stroma. Many tumor cells showed myoepithelial cell features by electron microscopy, and immunoreactivity for S-100 protein and GFAP was also seen in many of them. These findings were consistent with those of pleomorphic adenoma. However, the epithelial elements were cytologically atypical with prominent mitotic figures. Infiltration of the tumor cells into the surrounding soft tissue was also seen. No foci of benign pleomorphic adenoma were found in the primary tumor. These findings indicate that this tumor was not a carcinoma ex pleomorphic adenoma, but a true malignant pleomorphic adenoma (true malignant mixed tumor) of the trachea.

Aged

The lca as an onco-fetal gene: its expression in human fetal liver.

The lca-transforming DNA was isolated from human hepatocellular carcinomas. This gene has no homology with known transforming DNA from human sources, and its role in neoplastic tissue formation has been left unanswered. In this communication, we report that RNAs prepared from human fetal livers hybridize to the lca DNA probe. The RNA is 1.8 kilobase in size and appears in the fetal liver only for a limited period during its development, viz. 19 weeks through 24 weeks of gestation. No other tissues carry detectable levels of the lca messenger RNA. Fetal hepatocytes at 5 weeks of gestation showed no transcripts of lca, but upon culturing for 2 more weeks in vitro, the cells became producers of the lca messenger RNA. These results suggest that the lca plays some role in the proliferative stage of the liver.

Carcinoma, Hepatocellular

Effect of lidocaine on the asphyxial responses in the mature fetal lamb.

The effects of lidocaine on the fetal circulatory responses to asphyxia were evaluated in chronically instrumented pregnant sheep. Twenty-six preparations were studied. Animals were assigned to one of three groups. The animals in group I (N = 10) did not have umbilical cord occluders placed. Lidocaine at 0.1 mg X kg-1 X min-1 was infused to the mother for 180 min. The animals in group II (N = 11) had an umbilical cord occluder, which was inflated to induce fetal asphyxia (PaO2 15 mmHg) for 90 min. Occlusion was then maintained for an additional 180 min while lidocaine at 0.1 mg X kg-1 X min-1 was infused. The animals in group III (N = 5) also had an umbilical cord occluder inflated for 90 min. While occlusion was maintained for an additional 180 min, saline was infused, in place of lidocaine. The infusion rate of lidocaine of 0.1 mg X kg-1 X min-1 over 180 min resulted in a steady-state arterial lidocaine blood concentration in the mother of approximately 2.15 micrograms/ml. Fetal circulatory responses to asphyxia were evaluated before and after maternal infusion of lidocaine or normal saline. Measurements included heart rate, blood pressure, arterial pH, and blood gases. Cardiac output and organ blood flow were determined using the radio-labelled microsphere technique. In general, arterial and tissue lidocaine concentrations in asphyxiated fetuses were higher than those in the nonasphyxiated ones, the differences being significant in the brain, heart, liver, and adrenal glands.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural

[Heart metastasis of gallbladder cancer--a case report].

A 42-year-old man with gall bladder cancer was given a pancreatoduodenectomy. Chest-roentgenograms revealed a prominence of the left cardiac silhouette 6 months after operation. Two months later, the patient developed exertional dyspnea and chest pain. A diagnosis of heart metastasis of gall bladder cancer was established by aspiration cytology. Intravenous administration of 5-FU and cis-DDDP proved ineffective in controlling the disease. The patient died 14 months after operation. An autopsy revealed metastasis to the left ventricle of the heart. This is the 6th such case of gallbladder cancer in the literature.

Adult