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Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 235 records · Page 13Linked to original sources

Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model.

Various studies have demonstrated an increase in heat shock protein 70 (HSP70) synthesis in the brain following transiently induced ischemia, suggesting a protective role for HSP70 against ischemic insult. In this study, we determined the time course of HSP70 mRNA and protein induction in rat hippocampus following ischemia using Pulsinelli's four-vessel occlusion model, and suggested a protective role for HSP70 induction in limiting ischemic damage to neurons and delayed neuronal death. In Northern blotting analysis using human HSP70 DNA as a probe, the accumulation of HSP70 mRNA after 5 min ischemia became evident at 4 h, and continued until 16 h, while after 30 min ischemia, HSP70 mRNA appeared at 2 h, and continued above control level until 24 h after treatment. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 protein appeared 24 h and reached a maximum 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, staining was not detected in CA1 neurons until 16 h after 5 min ischemia, but staining in CA1 gradually increased 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in the staining pattern of HSP70 protein were observed in CA3 and CA4 neuronal cells following 30 min ischemia. When rats pretreated with 5 min ischemia (non-lethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, considerable staining of HSP70 was observed. Pretreated rats had much less neuronal damage in the CA1 sector than did rats subjected to lethal, 30 min ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Syrian hamster embryo cell lines useful for detecting transforming genes in mouse tumours: detection of transforming genes in X-ray-related mouse tumours.

The Syrian hamster embryo cell lines, SHOK and MC-1, were used as recipient cells for DNA transfection assay to detect transforming genes in experimental mouse tumours. A mouse repeat sequence was utilised to check whether each transformed focus included mouse genomic DNA in the Hamster background. We investigated five mouse tumours that are related to X-ray radiation, and detected activated c-K-ras, c-mos, and c-cot oncogenes which induced foci of hamster cells. These results show that SHOK and MC-1 cells have unique properties for detecting transforming genes in experimental mouse tumours.

3T3 Cells↗

[An epidemiological study on chronicity and incidence of hepatocellular carcinoma in the sequence of epidemic hepatitis].

From November 1951 to 1954, 416 patients in Kumayama Town, Okayama Prefecture, suffered from epidemic hepatitis, so-called "Kumayama Hepatitis". The mortality rate was 13.98% in the first one year, and the rate of progress to chronic hepatitis after 10 years was 24.6%. In the present study surveyed in 1991, 720 residents in this area had 13.6% positive anti-HCV (C100-3), significantly higher than in control areas. The rate of positive anti-HBs and abnormal liver functions in the subjects with positive anti-HCV was 42.9% and 40.8%, respectively. In 29 patients with clinically typical "Kumayama Hepatitis", the positivity rate of anti-HA IgG, anti-HBs, and anti-HCV, and the prevalence of abnormal liver function was 82.8%, 41.4%, 34.5%, and 10.3%, respectively. In conclusion, it is suggested that the hepatitis epidemic in Kumayama Town was caused by HAV and superinfected by HCV and/or HBV, then its clinical manifestations became complicated.

Adult↗

Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats.

The objective of this study was to evaluate the combined effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor (TNF) by alveolar macrophages. Rats were exposed to cigarette smoke in vivo, and production of TNF by alveolar macrophages was measured in the presence of mineral fibres in vitro. For smoke exposure, rats were divided into two groups. Five were exposed to a daily concentration of 10 mg/m3 of cigarette smoke for an eight hour period, and five rats (controls) were not exposed to smoke. Bronchoalveolar lavage was performed after exposure to smoke and the recovered alveolar macrophages were incubated with either chrysotile or ceramic fibres on a microplate for 24 hours. Activity of TNF in the supernatant was determined by the L-929 fibroblast cell bioassay. When alveolar macrophages were not stimulated by mineral fibres, production of TNF by rats exposed to smoke and unexposed rats was essentially the same. When alveolar macrophages were stimulated in vitro by chrysotile or ceramic fibres, production of TNF by alveolar macrophages from rats exposed to smoke was higher than that by alveolar macrophages from unexposed rats. The findings suggest that cigarette smoke and mineral fibres have a synergistic effect on TNF production by alveolar macrophages.

Aluminum Silicates↗

Disappearance of pulmonary metastases by OK-432 treatment in a case of hepatocellular carcinoma.

We report here a case of hepatocellular carcinoma (HCC) with multiple lung metastases, which were disappeared by treatment of OK-432. The patient was a 65-year-old man and was diagnosed in 1986 with a small (17 x 11 mm) HCC in the anterior-superior segment of the liver. A part of the right hepatic lobe including the tumor was surgically removed, and transarterial injections of adriamycin (10 mg/week) and subcutaneous injections of OK-432 (10 KE/week) were given. Two and a half years later, recurrence of HCC in the liver and its invasion to vena cava inferior (IVC) were found. OK-432 administration was then stopped and percutaneous ethanol injection therapy (PEIT) was performed 10 times. Six months later, the PEIT was effective and the liver tumor with IVC invasion diminished. However, multiple lung metastases were visible on roentgenograms of the chest, and serum alphafetoprotein (AFP) concentration increased to 50,000 ng/ml. The OK-432 treatment resumed. After 6 months of OK-432 treatment, the multiple lung metastases were disappeared and the serum AFP level decreased to 100 ng/ml. At present, the patient is surviving without any sign of recurrence in either the liver or the lung. The clinical course of this case suggests that OK-432 might have effectively treated lung metastases of HCC, although the exact mechanisms are at present unclear.

Aged↗

Recombinant mouse cytochromes P1-450 and P3-450: enzymatic characterization of the hemoprotein expressed in human cells infected with recombinant vaccinia virus.

We expressed mouse cytochrome P1-450 and P3-450 using recombinant vaccinia virus gene expression system in HeLa cells that were devoid of significant basal levels of P-450. HeLa cells were infected with the recombinant vaccinia virus containing either mouse cytochrome P1-450 or P3-450 cDNA, and the cell lysates were analyzed for the kinetics of P-450 enzyme activity and protein expression at the same time. 7-Ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were measured as an expression of the cytochrome P-450 enzyme activities. Both cell lines began to express these enzyme activities as early as 12h after infection. The activities increased linearly up to the 24 h time point, and were kept for 36 h. Western immunoblot analysis showed that these cytochrome P-450 proteins were detected at 16 h and reached maximum quantity at 24 h after infection. These data showed a good correlation between cytochrome P-450 enzyme activity and protein concentration throughout the process of P-450 gene expression by vaccinia virus vector, suggesting a complete formation of cytochrome P-450 holoenzyme from the early stage of the protein expression.

7-Alkoxycoumarin O-Dealkylase↗

Loss of ICG uptake in the process of rat hepatocarcinogenesis correlates to the disappearance of glutathione-S-transferase alpha subunit.

Reduced indocyanine green (ICG) uptake is one of the functional changes of human hepatocellular carcinoma (HCC). To clarify the mechanisms of loss of ICG uptake, and determine which subunit of glutathione-S-transferase (GST), alpha or pi, plays a role in ICG transport in hepatocytes, an experimental HCC model was developed that used nodules induced by 2-acetylamino-fluorene (2-AAF) administration. Many of the ICG stained nodules, which consisted of benign and borderline lesions, were GST-alpha positive. However, the percentage of GST-alpha positive cells tended to decrease according to the disappearance of ICG staining in the process of hepatocarcinogenesis. HCCs unstained by ICG were also GST-alpha negative. GST-pi, not detected in normal rat hepatocytes, appeared in an earlier stage of hepatocarcinogenesis before the disappearance of GST-alpha, and was not observed in HCCs. No significant relationship between ICG staining and GST-pi was recognized. These results suggest that GST-alpha synthesis is disturbed in the process of hepatocarcinogenesis and results in loss of ICG uptake in HCCs, and also indicate that GST-pi may be useful for early diagnosis of preneoplastic hepatocytes showing no roles in ICG transport.

Animals↗

Malignant pheochromocytoma with hepatic metastasis diagnosed 20 years after resection of the primary adrenal lesion.

A 59-year-old woman developed multiple hepatic tumors 20 years after resection of pheochromocytoma of the left adrenal gland. Thin-needle aspiration biopsy of the tumor at segment 2 of the liver under ultrasound control showed histology compatible to pheochromocytoma. Then, on the basis of the diagnosis of hepatic metastasis of malignant pheochromocytoma, transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastasis. After TAE, the size of the hepatic metastatic lesions was decreased. The present case suggests the necessity of long-term follow-up in pheochromocytoma cases.

Aclarubicin↗

Differentiation of discolouration in a body by an erythrocyte membrane component, glycophorin A.

In a differential study to distinguish antemortem bruise from postmortem infiltration of haemoglobin on the skin, a component of erythrocyte membrane, glycophorin A was extracted from experimental bruise and haemoglobin infiltration lesions over set periods of time. This extraction was accomplished by utilising anti-glycophorin A serum, after which the difference between the two lesions was evaluated. The glycophorin A was recovered from the bruise lesions satisfactorily up to the ninth to twelfth days and showed good resistance to putrefaction. In contrast, no glycophorin A was detected in haemoglobin infiltration lesions taken at any time. Glycophorin A was also detectable in human vital bruises which were taken in autopsies of four hours to ten days postmortem. These results suggest that a differential diagnosis of antemortem bruise and postmortem haemoglobin infiltration is possible in advanced stages of death.

Autopsy↗

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. I. Study design and results of the first cross-sectional observation.

A 4-year cohort study was designed to assess the exposure-effect relationship of working in polyurethane foam (PF) manufacturing factories with exposure to toluene diisocyanate (TDI) and its effects on the respiratory system. This paper describes the results of the first cross-sectional observations. The study population included 90 male workers who had been working in PF factories for 0.5-25 years (mean 13.3 years) (PF workers) and 44 reference workers in the same factories. The mean exposure concentration of TDI calculated from 129 personal samples was 3.2 ppb. Peak exposure excursions above 20 ppb occurred in 16 of 129 samples. Pulmonary function and its change during the working day as assessed by examining the forced expiratory flow-volume curve, respiratory impedance, and airway resistance and specific airway conductance were not different in the PF workers from those in the reference workers. Chest X-radiographs did not show any noteworthy radiological changes. Prevalences of "phlegm in winter," "nasal stuffiness or discharge in winter," and "irritation of eye and throat mucous membranes" were significantly higher in the PF workers. The findings indicate that TDI exposure at levels around 3 ppb may not adversely affect the pulmonary function over many years of exposure of those who are not hypersensitive to TDI. The causal chemicals inducing some respiratory and irritative symptoms could not be specifically identified since the PF workers were exposed not only to TDI but also to other irritative agents in the PF manufacturing processes.

Adolescent↗

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system.

Fifty-seven polyurethane foam manufacturing workers (PF workers) and 24 reference workers were followed for 4 years to clarify the effects on pulmonary function of working in PF factories with exposure to toluene diisocyanate (TDI). No significant differences in the average annual losses (AALs) of pulmonary function for 4 years were observed among the 28PF workers whose TDI exposure levels were very low (mean = 0.1 ppb, group L), the remaining 29 PF workers with mean TDI exposure of 5.7 ppb (group H), and the reference workers. However, 15 PF workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concentration of 8.2 ppb showed significantly larger AALs in percentage maximal mid-expiratory flow, forced expiratory volume in 1 s ratio to vital capacity (FVC), and forced expiratory flow at 25% of FVC than expected, and significantly larger AALs in some obstructive pulmonary function indices than those of the 14 remaining PF workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average (TWA) of 1.7 ppb, group L, and the reference workers. These findings suggest that the peak exposure excursion level of TDI might be important in inducing obstructive pulmonary function changes in the PF workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable.

Adult↗

Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution.

After 12 days of culture, VX2 carcinoma cells were inoculated into the liver of 16 rabbits; 14 days later, 131I-labeled iodized oil ([131I]-Lp) suspended in lipiodol was injected into the hepatic artery. Selective accumulation of the contrast material in the tumor for an extended time was evident on X-rays and hepatic scintiphotographs. The antitumor effect was remarkable. [131I]-Lp agents warrant further examination for their clinical usefulness. Internal radiation therapy by transcatheter hepatic arterial injection of [131I]-Lp (group A) was evaluated in 9 patients with hepatocellular carcinoma (HCC, tumor stage III or IV) associated with liver cirrhosis (LC) and compared with combination therapy of Lp-TAE (group B) in 18 patients with HCC (tumor stage III or IV) associated with LC. In group A, serum AFP levels dropped rapidly in eight of the nine patients who had an elevated initial level of more than 500 ng/ml. The average reduction in tumor size was 50% in eight cases as determined by computed tomography. Histological examination of one resected liver specimen at 3 months after the third injection of [131I]-Lp revealed microscopic features highly suggestive of a radiation effect in the [131I]-Lp-containing area. The 1-year survival value for patients with HCC was estimated at 49.0% using the Kaplan-Meier method. The survival of patients treated with internal radiation therapy tended to be better than that of those treated with Lp-TAE (P = 0.119).

Aged↗

Genetic polymorphism of human factor H (HF, beta 1H globulin) in Chinese Han population in northeast China.

The distribution of human factor H of serum phenotypes were studied using ultrathin polyacrylamide gel isoelectric focusing (PAGIEF) and subsequent immunoblotting techniques in 203 Chinese of Han population in Liaoning Province of northeast China. The gene frequencies of HF*A and HF*B were 0.4828 and 0.5172, respectively. All the observed numbers of the phenotypes were in agreement with the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies among Chinese, Japanese, and Caucasian populations were compared.

China↗

Long-term course of childhood epilepsy with intractable grand mal seizures.

Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 year of age) were followed up for more than 5 years. The children were divided into 3 groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies.

Child, Preschool↗

Determinant factor for clearance of ceramic fibres from rat lungs.

Deposition, clearance, retention, and durability of inhaled particles from lungs are known to be important factors for induction of pulmonary fibrosis or lung cancer. To study the deposition and clearance of alumina silicate ceramic fibres from the lung, male Wistar rats were exposed to ceramic fibre particles with a mass median aerodynamic diameter (MMAD) of 4.2 micron, for six hours a day, five days a week for two weeks. The average exposure concentration was 20.7 (standard deviation (SD) 4.5) mg/m3. The rats were killed at one day, three months, and six months after the end of exposure, and the fibre numbers and dimensions were measured with a scanning electron microscope. No significant differences in number and geometric mean length of residual ceramic fibres in the lungs were found between the groups. The geometric mean diameter, however, decreased according to the duration of the clearance period. These findings suggest that solubility of fibre contributes most in the clearance of the inhaled ceramic fibres from the lungs.

Animals↗

Biological monitoring of workers exposed to acetone in acetate fibre plants.

Concentrations of acetone in urine, alveolar air, and blood were measured by gas chromatography with flame ionisation detection for 110 subjects occupationally exposed to acetone (mean 372 ppm) in three factories. Significant relations were found between the time weighted average environmental concentration and the concentration in the biological samples. The strongest correlation was between the concentration of acetone in urine and the degree of exposure (r = 0.71, 95% CI 0.64-0.77). This suggests that urinary acetone concentration is the best biological index of occupational exposure to acetone.

Acetone↗

Rat liver nodules induced by 2-acetylaminofluorene lose an ability to take up indocyanine green in the process of hepatocarcinogenesis.

Indocyanine green (ICG) was injected into rat liver nodules induced by 2-acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG staining and cell atypism of liver nodules was examined by means of histology and DNA flow cytometry. After 2-AAF administration, many small nodules appeared on the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after the administration, but some nodules were not stained after 14 weeks. ICG-stained nodules histologically consisted of benign tissues and borderline lesions, and many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them showed "aneuploidy". In this way, it has been suggested that HCC could derive from hyperplastic nodules and that they might lose an ability to take up ICG in the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione-S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was well correlated with ICG staining in the nodules, suggesting that the loss of ICG uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the appearance of ICG unstained and aneuploid nodules was significantly inhibited in rats which were fed on diet containing Syosaiko-to after the administration of 2-AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was identified.

2-Acetylaminofluorene↗