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Biomedical subjects

S Manabe

Publications and source records attributed to S Manabe.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparative study of goitrogenic actions of 3-substituted 1, 2, 4-triazoles in rats.

Antithyroid actions of 3-amino-1, 2, 4-triazole (ATZ), 3-mercapto-1, 2, 4-triazole (MTZ) and 3-nitro-1, 2, 4-triazole (NTZ), which are substituents on the 3-position of 1, 2, 4-triazole (TZ), and those of the parental compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of colloid content and a proliferation of the follicular epithelia. The serum concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NTZ inhibited thyroid peroxidase activity both in vivo and in vitro. These antithyroid actions were the most remarkable in case of MTZ and were the least in case of NTZ. TZ had no effect on the thyroid function in vivo and in vitro. The results of Lineweaver-Burk analysis on the effect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ showed competitive inhibition. These results suggest that both MTZ and NTZ have goitrogenic effects on the thyroid through antiperoxidase action, such as ATZ. Thus, the 3rd carbon position of TZ is thought to be important for induction of goiter in rats. A comparison of the relationship between substituent on the 3-position of TZ and antithyroid activity shows that a mercapto moiety has more potent antithyroid action than an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the substituents.

Animals↗
PubMed1994

A case of intracytoplasmic edema of follicular epithelial cells in rat thyroid.

Hydropic change of follicular epithelial cells in the thyroid was observed in a female Fischer 344 rat. Microscopically follicular epithelial cells were characterized by edematous swelling with weakly eosinophilic and homogeneous cytoplasm. The cytoplasm was negative for periodic acid-Schiff reaction, and thyroxine- and thyroglobulin-immunohistochemical reactions. Electron-microscopically, a small amount of amorphous substance was noted in remarkably dilated rough-surfaced endoplasmic reticulum (r-ER), and slight regressive changes of cytoplasmic organella were also observed. These morphological changes may indicate that focal intracytoplasmic edema was occurred in r-ER, and that the change belonged to hydropic degeneration of the thyroid follicular cells in the thyroid.

Animals↗
PubMed1993

A fluorescent carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in human lens.

A fluorescent carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been identified in both human normal lenses and cataractous lenses. The total amounts of PhIP in normal lenses were 50.7 +/- 36.0 pg (n = 7) while those of PhIP in senile and diabetic cataractous lenses were 143 +/- 29.2 pg (n = 10) and 148 +/- 55.0 pg (n = 10), respectively. Although it was not possible to strictly compare the contents of PhIP among normal, senile and diabetic lenses, due to the limited numbers of normal lenses available, the mean total amounts of PhIP in normal lenses were the lowest among normal, senile and cataractous lenses when allowing for differences in age. Furthermore, there was a significant correlation between total amounts of PhIP in human lenses, and age of the lens, suggesting that the content of PhIP in human lens is increased with age. In all types of lenses, the concentrations of PhIP in the insoluble-protein fraction (pg mg-1 protein) were significantly higher than those in the water-soluble protein fraction. In addition, PhIP was formed when bovine lens was incubated at 37 degrees C under the presence of creatinine and glucose for various time periods, and the yield of PhIP during incubation was found to be time-dependent. The results from our study suggest that PhIP may be one of the age-related fluorogens in the human lens.

Adolescent↗
PubMed1993

Nucleic acids induce the formation of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system.

Effects of nucleic acids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in a model system. When a mixture of a certain amount of DNA or RNA, creatinine (1 mmol) and phenylalanine (1 mmol) in 10 ml of 50 mM phosphate buffer, pH 7.4, was heated at 60 degrees C for 4 weeks in a screw-capped vial, PhIP was produced, and the yield of PhIP was dependent on the heating time as well as the dose of nucleic acid added to the mixture. However, PhIP was not detectable in the mixtures without the presence of nucleic acids. Both deoxyribonucleotides and ribonucleotides tested induced the formation of PhIP under the presence of phenylalanine and creatinine, although bases of nucleic acids such as adenine and guanine did not induce PhIP formation. Moreover, we confirmed that 2-deoxy-D-ribose as well as D-ribose induced the formation of PhIP in the presence of creatinine and phenylalanine. These results indicate that nucleic acids can induce the formation of PhIP in the presence of creatinine and phenylalanine in the model system. Our data also suggest that pentose in nucleic acids may participate in PhIP forming reactions.

Carcinogens↗
PubMed1993

Effect of excess phenylalanine diet during pregnancy on fetal brain growth in rats.

The effects of 10 and 20% casein diets containing 7% phenylalanine (Phe) during pregnancy on fetal brain growth were examined in rats. Control pregnant rats were fed the casein diets ad libitum or in restricted amounts. Total food intakes during 21-day period in the Phe excess groups decreased to about 50% of those of the liberally fed control groups. In control rats given 10 and 20% casein diets, fetal brain weights (Y, mg) were significantly and hyperbolically correlated to total food intakes (g/21 days), conforming to the following equations: Y = -10283/X + 130.5 (n: 13, r = 0.89, p < 0.001) and Y = -4396/X + 130.4 (n: 15, r = 0.68, p < 0.005), respectively. Similar plots for rats fed 10 and 20% casein diets with Phe fell below these lines, meaning that fetal brain growth was impaired by both the decreased food intake due to excess Phe (nonspecific effect) and the toxicity of excess Phe per se (specific effect). Total amounts of RNA and protein and protein/DNA ratio decreased in the fetal brain from excess Phe dams, suggesting that protein synthesis of brain cells was disturbed. This may be partly due to the disruption of normal patterns of free amino acids observed in the fetal brains. Reduction of total DNA was also seen in fetal brain from excess Phe groups, meaning impaired proliferation. From above findings we concluded that proliferation and hypertrophy were impaired in fetal brain from excess Phe dams.

Amino Acids↗
PubMed1993

Effect of excess phenylacetate diet during pregnancy on fetal brain growth in rats.

The effects of phenylacetate (PA) on fetal brain growth were examined in pregnant rats receiving a 20% casein diet with 1.0, 1.5, 2.0 or 2.5% PA. Control rats were fed the 20% casein diet ad libitum or restricted to daily consumption of 9 and 6 g. In experimental groups of rats total food intake during pregnancy decreased, however the decrease was not so large as we had expected. By plotting the fetal brain weight (Y, mg) against maternal food intake (X, g/21 days) in control groups the following hyperbolic regression equation was obtained: Y = -4243/X + 124.6 (n: 18, r = 0.80, p < 0.001). Similar plots for excess PA rats fell below this line, indicating that prenatal fetal brain growth was impaired by an excess in PA per se specifically, as well as by decreased food intake nonspecifically. Administering the excess PA diets resulted in decreases in total RNA, total protein and RNA/DNA ratio in the fetal brain, whereas total DNA was unchanged, showing the impairment of protein synthesis, not proliferation. No remarkable changes in concentration and pattern of free amino acids in maternal plasma in excess PA groups were observed. Using a relation between total food intake during pregnancy and fetal brain weight, the extent of specific and nonspecific effects of excess PA and phenylalanine on brain growth was compared.

Amino Acids↗
PubMed1993

Effect of dietary proteins on zinc bioavailability in pregnant rats.

In order to clarify the effects of dietary proteins on zinc bioavailability during pregnancy, two experiments were carried out. In Experiment 1, changes in zinc retention due to pregnancy (difference in retention between pregnant and nonpregnant animals) during early-mid and late pregnancy were examined in rats fed 10 and 20% egg white diets. Total amounts of retained zinc due to pregnancy were about 1000 micrograms or slightly more, equal to the zinc content in the products of conception at term. However, extra zinc retention during late pregnancy ranged between only 20 to 40% of overall retention, suggesting that almost all zinc retained during early-mid pregnancy moved from the mothers to the fetuses near term. Zinc retention in early-mid and late periods of pregnancy was higher in pregnant than nonpregnant rats, due mainly to increases in intake and bioavailability. In Experiment 2, to examine the effects of quality and quantity of dietary proteins, pregnant rats were fed either 10 or 20% egg white (EW), whole egg (WE), casein (C) and soy protein isolate with or without methionine (SM and S, respectively) diets. Total zinc retention during pregnancy was affected by both zinc and nitrogen intakes, though the former effect was greater than the latter. Because rats fed the EW diets retained dietary zinc efficiently, a relationship between zinc retention (Y, microgram/100 g BW/21 d.) and zinc intake (X, microgram/100 g BW/21 d.) was also examined in the non-EW protein groups, resulting in the following regression equation: Y = 0.471X-1790 (n: 51, r = 0.81, p < 0.001). Dietary protein quality affected the food intake resulting in different zinc intake and retention during pregnancy. Zinc from EW diets was more available than from the other four protein diets, because similar plots for rats fed the 10 and 20% EW diets fell above this line. Reasons for efficient bioavailability of zinc in EW were discussed in connection with the forms of zinc in diets and the pancreatic or intestinal responses to ingested EW.

Animals↗
PubMed1993

Nutritional improvements of soy protein isolate by different levels of methionine supplementation in pregnant rats.

The effects of various levels (0, 0.3, 0.4, 0.5, 0.7, 1.0 and 1.5%) of methionine supplementation to a 10% soy protein isolate (SPI) diet were investigated in pregnant and nonpregnant rats in terms of body weight gain, food efficiency, net protein utilization (NPU), growth of the conceptuses and free methionine concentration in the dam's plasma. Supplementation of 0.3 to 0.7% methionine resulted in increases in the weights of the body, fetus and placenta and improvements of food efficiency and NPU in both groups of rats. The extents of increases or improvements of these parameters were more in pregnant rats than in nonpregnant rats, though they were similar in each group independent of the dietary methionine level. No beneficial effects on body weight gain, food efficiency or reproductive performance were observed in rats fed diets with 1.0 or 1.5% methionine. The concentrations of free methionine in the plasma were increased by methionine supplementation to the diet and were consistently higher in nonpregnant rats than in pregnant rats at each level of methionine supplementation. From these results, we proposed that a level of 0.5% methionine (intermediate between 0.3 to 0.7%) is optimal for supplementing 10% SPI diet for rats. The appropriateness of this level is discussed in relation with the methionine equipment of growing rats.

Animals↗
PubMed1992

HCV RNA and antibody to HCV core protein in Japanese patients with chronic liver disease.

We evaluated the prevalence of hepatitis C virus (HCV) RNA and antibody (anti-HCVcore) to the putative HCV core protein in Japanese patients with chronic liver disease. Sera were screened by solid-phase enzyme immunoassay with a recombinant HCV core protein and by the reverse transcription-polymerase chain reaction (RT-PCR) test which directly detects the HCV genome. Anti-HCV core was detected with high titers in 95% (69/73) of chronic non-A, non-B hepatitis, and 94% (65/69) of anti-HCVcore-positive patients had the genome. Anti-HCVcore was also found with lower titers in 24% (10/41) of chronic hepatitis B virus carriers, and three of them had the genome. Only one (3%) of the 35 patients negative for anti-HCVcore tested positive to RT-PCR. These findings indicate the overwhelming prevalence of HCV infection in Japanese patients with chronic non-A, non-B hepatitis and a close relationship between the presence of anti-HCVcore and chronic hepatitis C in this population.

Adult↗
PubMed1992

Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating.

A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L-phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low-temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine.

Acetaldehyde↗
PubMed1992

The effects of hyperthermia on the spinal cord.

This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function.

Animals↗
PubMed1992

Species difference in susceptibility to phorbol myristate acetate-induced leukopenia and lung injury: rat vs. dog.

Phorbol myristate acetate (PMA) was administered intravenously in a single dose to rats (400 micrograms/kg) and in a single and repeated doses to dogs (40 micrograms/kg). Severe leukopenia was observed in both species. The leukopenia in rats was due to a decreased number of both lymphocytes and neutrophils while the leukopenia in dogs was mainly due to a decreased number of neutrophils. The rats recovered from leukopenia much faster than the dogs. The dog which received a single injection developed focal fibrosis in the lungs. Rats showed only slight localized hemorrhage in the lungs, although the rats received a ten-fold larger dose of PMA than the dogs. Lungs of dogs which received multiple injections revealed severe hemorrhagic lesions in most alveoli. Lung lesions induced by PMA are thought to be mediated by activated leukocytes. This suggests that the severity of lung lesion correlates with the degree and duration of neutropenia. In conclusion, intravenous administration of PMA caused lung damage in rats and dogs. However, rats show much less sensitivity to PMA than dogs, resulting from the different response of leukocytes to PMA.

Animals↗
PubMed1992

Protein and energy metabolism in patients with progressive muscular dystrophy.

Studies were made on whether body weight loss in patients with muscular dystrophy is due to reduced intake and/or abnormal expenditure of energy. For this, food intakes and various physiological variables were surveyed in totals of 310 patients with Duchenne muscular dystrophy (DMD) of 11 to 29 years old and 28 patients with limb-girdle muscular dystrophy (LGMD) of 30 to 47 years old. Energy and protein intakes, expressed on a unit body weight basis, in DMD patients were comparable to, or higher than the allowances for age-matched healthy controls, whereas those in LGMD patients were 92 and 94% respectively of these allowances. The basal metabolic rate (BMR), expressed as kcal/kg/day, of DMD patients of all ages was higher than that of controls, the difference increasing with age, and being about 20 to 30% higher than that of controls in older patients with DMD. The BMR of LGMD patients was nearly normal. The maintenance requirements of conventional dietary protein in DMD and LGMD patients were 1.26 and 0.84 g/kg/day, respectively. These values were about 68 and 12% higher than the normal adult value (0.75 g/kg/day), indicating decreased protein utilization and increased protein catabolism. Daily excretion of urinary 3-methylhistidine (3MH) per unit muscle mass (micrograms/mg creatinine) by MD patients was significantly higher than that by controls, indicating increased degradation of muscle protein. The BMR, maintenance protein requirement and 3MH excretion of DMD patients suggest that DMD is a hypercatabolic disease. Comparison of the energy and protein intakes with the allowances estimated in consideration of increased requirements showed deficiencies of energy and protein in DMD patients. Thus, we conclude that the underweight of the DMD patients resulted from nutrient deficiencies due to hypercatabolism, despite their considerably high intakes of energy and protein, expressed as per kg body weight. These deficiencies were confirmed by demonstrating decreased concentrations of free essential amino acids, particularly branched chain amino acids, in their serum. The values of variables of LGMD patients were intermediate between those of DMD patients and control subjects.

Adolescent↗
PubMed1992

Predictions of energy intake and energy allowance of patients with Duchenne muscular dystrophy and their validity.

Patients with Duchenne muscular dystrophy are so malnourished that energy supplementation is crucial. Their degree of energy deficiency was assessed as difference between their energy intake and their energy allowance, which were deduced from easily measured parameters. A significant, negative relationship was found between the basal metabolic rate (BMR) (Y, %, BMR/standard BMR) and body weight (X, %, body weight/standard body weight) in the patients, from which the formula for the BMR was deduced to be Y = -1.116X + 174.5 (n = 202, r = -0.72, p less than 0.001). Thus, it is possible to estimate the energy allowance for individual patients by a factorial procedure from the presumed BMR and a factor for physical activity. In addition, their energy intake was calculated from a constant protein-energy % (14.6%) in their diet and nitrogen intake which was deduced from a significant positive correlation between their nitrogen intake (Y, mg/kg/day) and their nitrogen excretion in 24 h urine samples (X, mg/kg/day). This correlation conformed to the equation Y = 1.053X + 32.4 (n = 267, r = +0.76, p less than 0.001). The validities of the above predictions for energy intake and allowance were examined by plotting the degree of energy deficiency (% ratio of presumed intake/presumed allowance) against the concentrations of retinal binding protein, prealbumin and transferrin in the serum, because rapid turnover proteins are sensitive to energy deficiency. Significant positive correlations were obtained with both variables, suggesting that these predictions were valid.

Adolescent↗
PubMed1992

Elevation of levels of carcinogenic tryptophan pyrolysis products in plasma and red blood cells of patients with uremia.

The carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), have been measured in plasma and red blood cells (RBC) of patients with uremia and normal subjects by using a high-performance liquid chromatography (HPLC) method. In both uremic patients and normal subjects, these carcinogens have been detected in RBC as well as plasma. Trp-P-1 and Trp-P-2 levels in plasma of uremic patients were significantly higher than those of normal subjects. Moreover, these carcinogen levels in RBC (per hemoglobin) were significantly elevated in uremic patients in spite of the presence of severe anemia. These results suggest that patients with uremia are continuously exposed to higher levels of these carcinogens as compared with normal subjects. Our data also support the idea that these carcinogens in plasma and RBC are suitable for monitoring exposure levels in humans.

Adult↗