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Biomedical subjects

Y Sakamoto

Publications and source records attributed to Y Sakamoto.

At least 451 records · Page 25Linked to original sources

Lipid peroxidation in the liver of carcinogen-resistant rats.

Recently, we developed a new strain of rats that exhibit marked resistance to the hepatotoxic and carcinogenic actions of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) and some other carcinogens. In this work, we compared lipid peroxidation in the liver of these carcinogen-resistant (R) rats and the parental Donryu strain rats that are sensitive (S) to hazardous actions of these carcinogens. The liver microsomal fractions of the R group contained less amounts of polyunsaturated fatty acids. Microsomal lipid peroxidation in the presence of exogenous NADPH was much lower in R rats than in S rats. Liver microsomes of R rats were much less active than those of S rats also in producing 4-hydroxynonenal, carbonyl compounds and conjugated diene. The hepatic contents of ascorbic acid, glutathione, alpha-tocopherol and coenzyme Q in the R rats were similar to those in S rats. The activities of the free radical scavenger enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), in the two groups were also similar. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are both thought to function in disposal of these cytotoxic aldehydes. The liver microsomal and mitochondrial ALDH activities of the two groups were similar. The ADH activity of the liver cytosolic fraction of R rats was nearly twice that of S rats, as measured with 4-hydroxynonenal as substrate. The higher ADH activity may explain the decreased lipid peroxidation in R rats at least partly, if this enzyme is involved in lipid peroxidation.

Alcohol Dehydrogenase↗

Alanine dehydrogenases from two Bacillus species with distinct thermostabilities: molecular cloning, DNA and protein sequence determination, and structural comparison with other NAD(P)(+)-dependent dehydrogenases.

The gene encoding alanine dehydrogenase (EC 1.4.1.1) from a mesophile, Bacillus sphaericus, was cloned, and its complete DNA sequence was determined. In addition, the same gene from a moderate thermophile, B. stearothermophilus, was analyzed in a similar manner. Large parts of the two translated amino acid sequences were confirmed by automated Edman degradation of tryptic peptide fragments. Each alanine dehydrogenase gene consists of a 1116-bp open reading frame and encodes 372 amino acid residues corresponding to the subunit (Mr = 39,500-40,000) of the hexameric enzyme. The similarity of amino acid sequence between the two alanine dehydrogenases with distinct thermostabilities is very high (greater than 70%). The nonidentical residues are clustered in a few regions with relatively short length, which may correlate with the difference in thermal stability of the enzymes. Homology search of the primary structures of both alanine dehydrogenases with those of other pyridine nucleotide-dependent oxidoreductases revealed significant sequence similarity in the regions containing the coenzyme binding domain. Interestingly, several catalytically important residues in lactate and malate dehydrogenases are conserved in the primary structure of alanine dehydrogenases at matched positions with similar mutual distances.

Alanine Dehydrogenase↗

Suppressive effect of adrenalectomy on growth of L1210 leukemic cells in ascites.

This study was designed to evaluate the effect of adrenalectomy on growth of L1210 leukemic cells in ascites of BDF1 mice. Varying doses of 1.5 x 10(4), 5.0 x 10(5), and 1.5 x 10(6) viable tumour cells were inoculated intraperitoneally into groups of either adrenalectomized or sham-operated mice. At days 4 to 7 after the inoculation, adrenalectomized mice inoculated with 1.5 x 10(4) or 5.0 x 10(5) tumour cells had a smaller number of tumour cells in ascites than sham-operated controls. However, after inoculation of 1.5 x 10(6) cells, no significant differences were found at days 2 to 4 between adrenalectomized and sham-operated mice. The growth retardation by adrenalectomy was not observed in adrenalectomized mice supplemented with 4 or 6 micrograms dexamethasone per day per mouse. It suggested that the ablation of glucocorticoids was at least partially responsible for the growth retardation observed in adrenalectomized mice. Cell kinetic analysis revealed that the difference in a potential doubling time could not explain these results. Tumour retention in the peritoneal cavity was measured using [125I]-iododeoxyuridine-labelled tumour cells as a tracer. At days 4 to 6 after inoculation of 5.0 x 10(5) labelled cells, radioactivity in the peritoneal cavity in adrenalectomized mice was about 70 per cent of that in sham-operated mice. This ratio was almost equivalent to the ratio of the number of cells in ascites of adrenalectomized mice to that of sham-operated ones. Consequently, growth retardation observed in adrenalectomized mice resulted from an increase in tumour cell migration and/or in tumour cell death, but not from an increase in doubling time.

Adrenalectomy↗

Unusual trihydroxy bile acids in the urine of patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and those with cirrhosis.

Urinary bile acids from 20 patients treated with chenodeoxycholate, 18 treated with ursodeoxycholate, 15 treated with rifampicin and 8 patients with advanced cirrhosis were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry. Occurrence rates and amounts of three so-called unusual trihydroxy bile acids, hyocholate, ursocholate and omega-muricholate, were increased in patients treated with chenodeoxycholate, ursodeoxycholate or rifampicin and decreased in cirrhotic patients as compared with those in untreated healthy adults. These data suggest that chenodeoxycholate and ursodeoxycholate are hydroxylated to produce unusual trihydroxy bile acids in bile acid-loaded humans and that this metabolism may be related to the induction of hepatic microsomal enzymes by rifampicin. In contrast, the hydroxylation of chenodeoxycholate and ursodeoxycholate may be impaired by severe hepatic damage. Because the urine is a secretory pathway for internal bile acids, the occurrence of unusual trihydroxy bile acids in the urine may be used as an indicator of hepatic ability to metabolize "hydrophobic" dihydroxy bile acids to their secretory forms.

Bile Acids and Salts↗

Electron microscopic study of the effect of capsaicin on the mouse chorda tympani nerves.

Studies were made to determine whether this nerve contains capsaicin-sensitive fibres. Capsaicin (50 mg/kg, subcutaneously) was injected into 2 animals on day 2 after birth and into one animal on days 2 and 3 after birth. Both chorda tympani of these and 4 control mice were later excised. The constituent fibres of 3 of the capsaicin-treated and all 8 control nerves were then analysed. The myelinated fibres in 3 chorda tympani of treated and control animals were measured, and the unmyelinated axons in Schwann cells were counted from electron-micrograph montages of the entire nerve. Normal chorda tympani contained about 600 nerve fibres, 55% myelinated and 45% unmyelinated. Capsaicin-treatment did not change the constituent fibres nor the size distribution of the myelinated fibres. Thus no capsaicin-sensitive, nociceptive fibres were found in the mouse chorda tympani. Capsaicin does not destroy the neurones of the geniculate ganglion and parasympathetic, presynaptic fibres. Therefore, gustation and secretion of saliva are not influenced by capsaicin.

Animals↗

Phosphorylation of P0 glycoprotein in peripheral nerve myelin.

The P0 protein in mammalian PNS myelin is known to undergo several posttranslational modifications, such as glycosylation, acylation, sulfation, and phosphorylation. Phosphorylation of purified P0 protein in vitro was studied comparatively using three enzymes, i.e., calcium/phospholipid-dependent protein kinase (protein kinase C), calcium/calmodulin-dependent protein kinase II (CaM kinase II), and the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase). The phosphorylation of P0 protein by CaM kinase II was the greatest, followed by that by protein kinase C; phosphorylation by A kinase, however, was much lower. In order to identify phosphorylation sites, P0 protein was phosphorylated with [32P]ATP and each kinase and then digested with lysylendopeptidase. The resulting phosphopeptides were isolated by HPLC. Subsequent amino acid sequence analysis and comparison with the known sequence of P0 protein revealed that Ser181 and Ser204 were strongly phosphorylated by both protein kinase C and CaM kinase II. In addition, Ser214 was also phosphorylated by protein kinase C, but not by CaM kinase II. Because all of these sites are located in the cytoplasmic domain of P0 protein, phosphorylation may be important for maintenance of the major dense line of PNS myelin.

Amino Acids↗

Calcium-associated cytoprotective effect of taurine on the calcium and oxygen paradoxes in isolated rat hepatocytes.

Our study was designed to determine the calcium and oxygen paradoxes in isolated rat hepatocytes, and to evaluate the cytoprotective effects of taurine on hepatocytes during oxygenation, hypoxia, and on these paradoxes. The calcium and oxygen paradoxes were clearly revealed in isolated rat hepatocytes. As the formation of the superoxide radical was accelerated by the hyperbaric conditions and the calcium ions, drugs such as superoxide dismutase and a calcium channel blocking agent (verapamil), prevented these paradoxes. Taurine decreased the oxygenation-induced lipid peroxidation of hepatocytes, and prevented the hypoxia-induced hepatocyte death in a calcium-containing medium, but not in a calcium-free medium. Taurine also protected the hepatocytes from injuries associated with the calcium and oxygen paradoxes due to the inhibition of sudden calcium influx into the hepatocytes.

Animals↗

Spinal cord compression due to ossification of ligaments: MR imaging.

A total of 108 patients with ossification of the posterior longitudinal ligament (OPLL) (n = 92), ossification of the yellow ligament (OYL) (n = 8), or both (n = 8) were examined with magnetic resonance (MR) imaging performed with 0.5-T superconductive and 0.22-T resistive units. OPLL was demonstrated as a low-signal-intensity band between the bone marrow of the vertebral body and the dural sac on T1- and T2-weighted images. Continuous cervical OPLL was easier to diagnose than segmental cervical OPLL. T2-weighted images were more useful for detection of ossification of the ligaments. OYL was recognized as an impression on the posterior dural sac. Formation of bone marrow within an area of ossification, shown as increased or intermediate signal intensity, was observed in 56% of the cases of continuous OPLL, 11% of the cases of segmental OPLL, and none of the cases of OYL. The degree of cord compression was more severe in continuous OPLL. Degeneration of the disk was frequently associated with both types of OPLL.

Adult↗

Chronic injuries of the spinal cord: assessment with MR imaging.

Seventy-six patients with persistent myelopathy secondary to chronic spinal cord injuries underwent examination with magnetic resonance (MR) imaging, the results of which were correlated with neurologic findings. Twenty-one patients received follow-up study during and after the acute stage; 55 patients were examined only at a chronic stage. Spinal cord abnormalities were seen in 48 patients according to five patterns: (a) normal signal intensity on T1- and T2-weighted images (pattern N/N, n = 28), (b) normal signal intensity on T1-weighted and hyperintensity on T2-weighted images (pattern N/Hi, n = 18), (c) hypointensity on T1-weighted and hyperintensity on T2-weighted images (pattern Lo/Hi, n = 17), (d) cord atrophy (n = 5), and (e) longitudinal syrinx formation with hypointensity on T1- and hyperintensity or isointensity on T2-weighted images (n = 8). Patients with pattern N/N had only slight neurologic damage and an excellent prognosis. Patients with pattern N/Hi had mild neurologic impairment, frequently associated with cord compression. Patients with pattern Lo/Hi had the worst prognosis. Atrophy was observed in patients with a long history of myelopathy.

Adult↗

Effects of anoxia and low free fatty acid on myocardial energy metabolism in streptozotocin-diabetic rats.

To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization.

Adenosine Triphosphate↗

The multi-purpose camera: a new anterior eye segment analysis system.

A new device for the analysis of the anterior eye segment was developed. With this device, a Scheimpflug slit image and a retroillumination image can be taken separately using a CCD camera. The quality of the images obtained was satisfactory enough for analysis. The data obtained were stored and analyzed on an almost real-time level using an on-line computer. The menu for the data analysis provided for this device includes multilinear densitometry, with planimetry, area densitometry, measurement of anterior chamber depth and thickness of lens layers, determination of chamber angle and positioning of implanted intraocular lenses, and measurement of opaque areas in the retroillumination image.

Animals↗

Evaluation of nuclear opacification using a lens opacity meter.

The lens opacity meter, a recently developed clinical device for the examination of cataractous lenses, was used to evaluate nuclear opacification. In 215 noncataractous lenses of subjects aged 6-86 years, the opacity value (OV) ranged from 5.2 to 24.8 and increased with ageing. The OV measured in cortical cataracts with intrapupillary opacification was relatively higher than that without opacities. The scattered light intensity of the nuclear zone, measured from a Scheimpflug image, correlated well with the OV. In some cases with noncataractous eyes, the correlation between small-sized protein particles and the OV was examined. The lens opacity meter is useful to objectively evaluate changes in nuclear opacity.

Adolescent↗

Comparison of retroillumination images of crystalline lenses taken with different camera types.

Cataractous lens images taken with different camera types for retroillumination photography were compared. Images taken by conventional photo slitlamp and fundus cameras were not suitable for image analysis. Retroillumination photography with a conventional fundus camera with additional polarizing filters seemed to be useful as a daily clinical routine examination. The image quality obtained from devices especially designed for retroillumination photography was almost the same, providing material for further analysis. An anterior eye segment analysis system gave high-contrast images and less background variations of image density.

Cataract↗

A new analysis method for cataractous images taken by retroillumination photography.

Photographic data have been used to diagnose cataracts. In particular, retroillumination photographs are popular and useful owing to their clearness of whole images of crystalline lenses at a glance. A new procedure called grid method for the quantitative analysis of retroillumination photographs is proposed here. With this method a ratio of cataractous area to total area can be calculated by separating an image of a lens in grids, with a greater precision compared with the usual threshold method. Furthermore, based on a correlation check of the grid number and the resulting accuracy we determined that 25 grids is the optimal cutting for our grid method.

Cataract↗

Quantitative chamber angle measurement utilizing image-processing techniques.

An image-processing technique was applied to the measurement of the anterior chamber angle. The anterior eye segment was documented by a new instrument, named anterior eye segment analysis system for biometry of the anterior eye segment. The approximated curve of the corneal posterior curvature and the line tangent to the anterior surface of the iris were calculated as the anterior chamber angle. The mean error of the reproducibility of repeated measurements for the same image was 1.6 +/- 0.81% and that of 3 images of the same eye which were taken at 3 different times was within 5.2%.

Adult↗

[Relative weight and mortality during a five-year follow-up study in an aged population--a study of aged inhabitants of a rural area in Japan].

The present study, a follow-up study for 669 aged examinees of a health check performed in July 1983 in a rural area in Fukushima Prefecture, was conducted to clarify the relationship between relative weight and mortality among aged individuals living in a Japanese rural area. Using the standard body weights calculated from Japanese mean body weights by sex, age class (60-69 and 70 or more) and height cited from the data of the Ministry of Health and Welfare from 1966, mortalities during the five year follow-up were compared among four groups different in relative weight at baseline. The results are as follows. 1) The mortalities in the group of 'Relative weight less than or equal to -10% the leanest group among the four groups, were highest in both sexes, 52.8 per 1000 person-years for males and 33.2 per 1000 person-years for females. On the other hand, those in the group of '+10% less than or equal to Relative weight less than +20%' were lowest in both sexes, 23. 1 per 1000 person-years for males and 7.0 per 1000 person-years for females. In females, the difference in the mortality between these two groups was statistically significant at the 0.05 level, provided age structures in both groups were taken into consideration. 2) In both sexes, the mortalities of cancer and cerebrovascular disease in the group of 'Relative weight less than or equal to -10%' were highest among the four groups, whereas such mortalities in the group of '+10% less than or equal to Relative weight less than +20%' were lowest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Mechanisms of the depolarization and contracture due to Na removal in the circular muscle of the guinea-pig stomach.

Verapamil (10(-6) M) significantly reduced a development of the membrane depolarization and the contracture which were induced by Na removal. The fully developed depolarization, after exposure to Na-free solution, was reduced greatly by verapamil, excess Ca (15 mM) or sodium nitroprusside (10(-6) M), but some depolarization still remained. This remaining depolarization was completely blocked by readmission of 10 mM Na to Na-free solution containing verapamil, excess Ca or sodium nitroprusside. However, Mn (1.5 mM) did not block the depolarization due to Na removal and if Mn was present in Na-free solution, readmission of 15 mM Na to Na-free solution was not able to block the depolarization. On the other hand, the contracture due to Na removal was inhibited by addition of Mn (1.5 mM) or sodium nitroprusside (10(-6) M), but partially by addition of verapamil (10(-6) M) or excess Ca, to Na-free solution. These remaining contractures were also abolished by readmission of 10 mM Na to Na-free solution containing verapamil or excess Ca. Thus, these results suggest that the depolarization and the contracture due to Na removal are induced by increase in cytoplasmic Ca concentrations through (1): verapamil-sensitive Ca channel, (2): Na-Ca exchange system and (3): some mechanism which is inhibited by sodium nitroprusside.

Animals↗