Studies on Habu snake venom. VII. Heat-stable myolytic factor and development of its activity by addition of phospholipase A.
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Biomedical subjects
Publications and source records attributed to Y Hara.
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A bio-antimutagen, isolated from Japanese green tea (leaves of Camellia sinensis), reduced high spontaneous mutations due to altered DNA-polymerase III in a mutator strain of Bacillus subtilis. Chemical studies showed that the factor was epigallo-catechin-gallate (EGCg).
Theaflavins, polyphenolic ingredients of black tea, were observed to inhibit in vitro lipid peroxidation in the erythrocyte membrane ghost and microsomal systems. Theaflavins also showed inhibition of DNA single-strand cleavage and mutagenicity, both induced by hydrogen peroxide. These results suggest that theaflavins scavenge radicals to produce antioxidative and antimutagenic effects. It was also found that the gallic acid moiety of theaflavins is essential for their potent antioxidative activities.
The purpose of the present study was to elucidate the characteristic lipoprotein disorder in essential hypertension. Twenty-six patients with essential hypertension (HT) but without diabetes mellitus or obesity and 24 healthy subjects (control) were recruited into this study. Lipoproteins of HT and controls were separated by ultracentrifugation to very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low-density liproprotein (LDL), and (HDL) fractions. Cholesterol and triglycerides were determined with enzyme assay, and apoB were determined by highly sensitive latex agglutination (Kyowa-hakko Co. LD). There was no difference in age (mean +/- SE; HT, 63 +/- 2 versus control, 60 +/- 2 years) or body-mass index (22.7 +/- 0.4 versus 21.7 +/- 0.5 kg/m2) between HT and controls. Blood pressure in HT and controls was 158 +/- 2/87 +/- 12 mm Hg and 123 +/- 3/72 +/- 2 mm Hg, respectively. Cholesterol did not change significantly in plasma (192.1 +/- 7.0 versus 176.4 +/- 4.2 mg/dL), VLDL (15.2 +/- 2.4 versus 11.8 +/- 1.7 mg/dL), IDL (14.8 +/- 2.4 versus 10.7 +/- 1.6 mg/dL), LDL (93.7 +/- 4.6 versus 83.1 +/- 3.9 mg/dL), nor in HDL (51.9 +/- 2.7 versus 58.1 +/- 3.2 mg/dL). Triglycerides (TG) increased in plasma (120.0 +/- 10.0 versus 87.5 +/- 9.3 mg/dL, p < 0.05), although TG did not change in all subfractions. ApoB increased in plasma (105.5 +/- 5.1 versus 85.6 +/- 3.6 mg/dL, p < 0.01), IDL (9.0 +/- 1.3 versus 5.4 +/- 0.6 mg/dL, p < 0.05), and LDL (76.3 +/- 4.3 versus 59.4 +/- 3.7 mg/dL, p < 0.01) in HT compared with controls. The ratio of cholesterol to apoB in LDL decreased (1.27 +/- 0.06 versus 1.48 +/- 0.08, p < 0.05). In essential HT, number of apoB containing lipoproteins (IDL, LDL) increased. Low ratio of cholesterol to apoB was noted in LDL, indicating the presence of small, dense LDL. As cholesterol in LDL was normal, hyperbetalipoproteinemia is also a characteristic disorder of essential HT.
INTRODUCTION: The protective role of nitric oxide (NO) against hepatic ischemia-reperfusion (I/R) injury remains controversial. In this study we investigated the effect of tetrahydrobiopterin (BH4) on the survival of rats exposed to an hepatic I/R injury. METHODS: The rats were subjected to 100 minutes of 70% hepatic ischemia 30 minutes after administration of BH4 or saline. A specific inducible NO synthase (iNOS) blocker, 1400W, was used to evaluate endogenous iNOS. NOS protein measured the histological appearance of the liver by Western blotting, and survival was evaluated after reperfusion. RESULTS: The 1-week survival rate was 60% among the BH4 group and 10% for the saline group. The serum ALT and bilirubin values in the BH4 group were significantly lower than the saline group. Histological examination of the liver revealed only a small necrotic area in the BH4 group as opposed to massive necrosis and cell infiltration in the saline group. Injection of 1400W significantly decreased the prolongation of survival produced by BH4. CONCLUSIONS: BH4 significantly improved the survival rate, the histological findings, and the liver function, thereby reducing liver failure. Western blotting showed a higher level of iNOS protein in the BH4 group than the saline group, 1400W suppressed this effect of BH4. Taken together, these observations suggest that NO derived from reactions driven by BH4-induced iNOS exerts a protective effect against reperfusion injury.
We previously reported that mouse embryonic stem (ES) cells are capable of differentiating into hepatocytes in cultured embryoid bodies (EBs) and that hepatocytes generate in the recipient liver injected with cultured day-9 EB cells via spleen without the formation of a teratoma. Because ES cells frequently form teratomas in recipient mice, we investigated incidence of teratoma formation when day-9 EBs derived from ES cells were transplanted directly into the subcapsule of mouse liver. In contrast to injection of day-9 EB cells through the portal vein via the spleen, direct subcapsular injection of cultured day-9 EB cells into liver, and even of cultured day-15 EBs, resulted in an high incidence of teratoma in the liver. In teratomas of livers injected directly with day-15 EBs, hepatocytes were detected singly and in clusters. These results imply that undifferentiated cells capable of developing into teratomas exist in cultured EBs, and even in cultured day-15 EBs containing differentiated hepatocytes.
Respiratory complications, such as pneumonia and atelectasis, are major causes of mortality and inhibit rehabilitation programs in spinal cord injury. Tetraplegic patients cannot cough enough to clear their sputum because of expiratory muscle weakness, mainly of the abdominal muscles. However, tetraplegics are still able to activate some muscles during coughing. Some tetraplegics, even though they cannot contract the abdominal muscles, can cough effectively. It was supposed that some accessory expiratory muscles were activated during coughing in tetraplegics. We, therefore, studied the peak expiratory flow rate, expiratory muscle strength, and the activities of the pectoralis major and latissimus dorsi muscles in 11 complete tetraplegics. Peak expiratory flow rate was measured by spirometry. Expiratory muscles strength was assessed by maximal expiratory mouth pressure; muscle activity was assessed by means of the root mean square voltage obtained by surface electromyography. The results showed that peak expiratory flow rate, maximal expiratory mouth pressure, and root mean square of these two muscles were correlated with neurological level. Peak expiratory flow rate was correlated with peak expiratory flow rate. Peak expiratory flow rate was correlated with the root mean square voltage of the pectoralis major and latissimus dorsi muscles. It was supposed that these two muscles were activated as accessory expiratory muscles and play an important role in expiratory function in tetraplegic patients.
We report the demonstration by magnetic resonance (MR) imaging of brain involvement in two of four subjects with human T-cell lymphotropic virus type I (HTLV-I) associated myelopathy. The four cases had slowly progressive spastic paraparesis, urinary incontinence, and positive HTLV-I antibodies in serum or CSF or both. Magnetic resonance revealed areas of abnormal intensity in the cerebral hemispheres of two of these cases; one of them also showed brain stem involvement. No spinal cord lesion could be detected in any case by MR.
Brainstem auditory evoked responses (BAERs) to click and tone-burst stimuli (0.5, 1, 2, 4, and 8 kHz) were recorded from 32 ears in 16 adult Beagles. BAERs were used to establish a normative database and describe response thresholds and latencies (wave I-IV) for the different stimuli. The frequencies of sound used were 8, 4, 2, 1, and 0.5 kHz. Sound stimuli were delivered by a closed headphone and masking stimuli were not applied. The BAER waveforms obtained were similar to those reported previously, except for a frequency-following response evoked by 1-kHz tone-bursts. The threshold was lowest when clicks and 4-kHz tone-bursts were used. Significant differences were observed between the mean values of the peak latencies for clicks and 4- and 8-kHz tone-bursts. The tone-burst stimulation used in our experiment was shown to be an appropriate method for detecting the BAERs. Thus, for investigating the frequency-specificity of the auditory sense, BAER data obtained using tone-burst sound in dogs may be meaningful.
The cardiorespiratory responses to weight reduction due to physical exercise were examined in fourteen women with obesity, aged 36 to 67 years (Body Mass Index, 32.4 +/- 1.5 kg/m2). The patients were instructed to exercise at approximately 60% of maximum oxygen uptake for 2 h every day for approximately 3 months. To evaluate physical strength, a graded cycling exercise test was performed both before and after the exercise period, monitoring gas exchange, ventilation, and heart rate. After the exercise period the body mass index and percentage fat both decreased by 11% and 18%, respectively (P < 0.001), although lean body mass did not change; maximum oxygen uptake and maximum heart rate did not change significantly, but peak ventilation equivalent, maximum metabolic equivalent and maximum load increased by 12%, 14% and 11%, respectively (P < 0.05, P < 0.001 and P < 0.001, respectively). Maximum oxygen uptake per unit body weight increased by 5% (P < 0.001). These results suggest that weight reduction as a result of exercise improves cardiorespiratory function in middle-aged women with obesity.
Exercise testing was used to examine 19 cardiorespiratory diabetes mellitus patients, aged 32-68 years (body mass index, 27.8 +/- 4.8 kg/m2), and 16 healthy volunteers, aged 23-57 years (body mass index, 22.7 +/- kg/m2). A graded cycling exercise test was done, monitoring gas exchange, ventilation and heart rate. Values were significantly higher in the non-insulin-dependent diabetes mellitus (NIDDM) patients than in the controls for fasting blood glucose (P < 0.01), glycosylated haemoglobin (P < 0.01), body weight (P < 0.05) and body mass index (P < 0.05). The exercise testing produced values that were significantly lower in the patients with NIDDM than in the controls for percentage oxygen uptake (P < 0.05), maximum load (P < 0.05), maximum metabolic equivalent (P < 0.01) and maximum oxygen uptake per unit body weight (P < 0.01). Ventilatory capacity and forced expiratory volume at 1 sec did not differ significantly in the two groups. These results suggest that general fitness is diminished due to reduced cardiorespiratory function in patients with NIDDM.
The first case of isolated thyrotropin (TSH) deficiency with Cushing's syndrome was reported. A 46-year-old female was admitted to our hospital because of fatigability, puffy eye-lids, leg edema and petechia. She was treated with thyroid hormone. A low free triiodothyronine continued. Serum TSH was undetectable and serum thyrotropin releasing hormone (TRH) was elevated. No response of serum TSH and normal response of serum prolactin after administration of exogenous TRH suggested the abnormalities of anterior pituitary gland. The secretion of growth hormone and gonadotropin were intact, but the secretion of adrenocorticotropic hormone (ACTH) was impaired. A high level of serum cortisol, no response of serum ACTH by metyrapone test and a tumor mass of abdomen detected by computed tomography led to the diagnosis of Cushing's syndrome. Histological examination of the tumor revealed adrenal adenoma. Twenty two months after the surgery, serum ACTH level was normalized, but the secretion of serum TSH to exogenous TRH was still absent. The results indicated that hypothyroidism in our patient was due to isolated TSH deficiency.
The exposure of human stomach cancer KATO III cells to green tea catechin extract and epigallocatechin gallate (EGCG), a main component of the extract led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological changes showing apoptotic body were observed in the cells treated with green tea catechin extract and EGCG. The fragmentation of DNA to oligonucleosomal-sized fragments, characteristic of apoptosis was determined to be concentration- and time-dependent. These data suggest that drinking of green tea in large amounts is recommended possibly to protect humans from stomach cancer.
A 50-year-old woman with antiphospholipid antibody syndrome (APAS) awoke in a morning to notice dizziness, so she came to our hospital. Several hours later she developed left oculomotor paralysis. Further two hours later she developed right oculomotor paralysis and could not stand. Brain MRI showed high signal intensity lesion of paramedian thalamic and midbrain on the T2-weighted image. Cerebral angiography did not reveal any occlusion. Transesophageal echocardiography disclosed mitral valvular vegetation. We thought this valvular abnormality was non-bacterial thrombotic vegetation associated with APAS and this suggests that cerebral infarction was due to emboli from this vegetation.
BACKGROUND: Thymidylate synthetase and thymidine kinase are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. MATERIALS AND METHODS: Weekly injections of 1,2-dimethyl-hydrazine induced high incidence of colorectal adenocarcinomas in rats. RESULTS: An increased activity of thymidylate synthetase was found in the poorly differentiated adenocarcinomas of the chemically induced rat colorectal tumors. Six-week oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) reduced the total number of colorectal tumors, with the reduction of thymidylate synthetase activity in the poorly-differentiated type, though the mRNA expression of thymidylate synthetase and thymidine kinase differed little between the groups with or without UFT treatment. CONCLUSIONS: These results indicate that the long-term oral administration using UFT suppresses colorectal carcinogenesis and the growth of the poorly-differentiated type tumors.