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Biomedical subjects

S Manabe

Publications and source records attributed to S Manabe.

At least 91 records · Page 5Linked to original sources

[The crystallinity of hypomineralized rat enamel caused by fluoride administration].

It has been well known that there are extreme amounts of inter-crystalline spaces and large amounts of enamel matrix in fluorosed human enamel. Our previous study discussed the fact that amelogenins in developing fetal enamel matrix protein may have a role in regulating or controlling enamel crystal growth. These results positively suggest that amelogenins degradation may be associated with the etiology of fluorosed enamel. The purpose of this study was to examine the relationship of the crystallinity of fluorosed enamel of rats and the molecular weight of enamel matrix protein. The crystallinity of fluorosed enamel of rats, caused by the ingestion of fluoride containing water was evaluated with the microbeam x-ray diffraction analysis and the molecular weight of enamel matrix protein was examined by SDS-polyacrylamide-gel electrophoresis. The results obtained in the study are summarized as follows. 1) The plasma fluoride level of rats increased linearly with the fluoride concentration in the drinking water. 2) The microradiographs of maturing incisor enamel of the group with 100 ppmF- and 200 ppmF- injected showed diffused radiolucent zone from the subsurface toward the dento-enamel junction. The disturbances in enamel mineralization were most apparent in the 200 ppmF- group. 3) The crystallinity of the radiolucent zone of the fluorosed enamel decreased in both the a and c-axis directions, and particularly decreased more in the a-axis compared with the control. 4) The pattern of the SDS-polyacrylamide gel electrophoresis of the enamel protein in the mature stage showed higher remaining molecular weight of amelogenins in rats in the 100 ppmF- and 200 ppmF- group. These results suggest that in hypomineralized enamel caused by long-term administration of fluoride containing water, the degradation of amelogenin protein was disturbed, and consequently the crystallinity of enamel apatite decreased.

Amelogenin↗

[Changes in the muscle fiber conduction velocity (MFCV) due to the masticatory muscle development. 1. Preliminary study in adults].

The purpose of this study was to investigate the methods involved in observing the muscle fiber conduction velocity (MFCV) both in the masseter muscle and the m. biceps brachii in healthy persons. Three adults were the subjects in this study, none of whom had any gnathofacial dysfunction. The EMG activities were recorded from the m. biceps brachii with the arm bent at right angles and the masseter muscle in the intercuspal position, in both muscles during 50% of maximum voluntary isometric contraction on the habitual side. Three types of surface electrodes were used. Type 1. the disc type electrodes array arranged straight, Type 2. the disc type electrodes array arranged independently, Type 3. the strip type surface electrodes array arranged straight. The EMG activities preamplified at three conditions of time constant, e.g., 0.003, 0.01, 0.03 sec on m. biceps brachii were analyzed through a personal computer system and a FFT analyser. The conduction velocity was calculated by the cross-correlation method. The results obtained in this study were as follows: 1) No differences in the MFCV between the time constant were noticed. 2) The electrode array arranged straight was effective in the measurement of the MFCV in adults and in particular the strip type series electrodes array arranged straight was the most effective to measure the MFCV in the masseter muscle. 3) The average MFCV of the m. biceps brachii and the masseter muscle were 4.13 +/- 0.29 m/sec and 14.28 +/- 1.21 m/sec respectively.

Adult↗

Antagonism of gamma-aminobutyric acidA receptor-mediated responses by amino-gamma-carbolines.

The amino-gamma-carbolines 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole were demonstrated to be potent convulsants. Administered i.p. in rats, these compounds penetrated the blood-brain barrier rapidly and appeared in the cerebrospinal fluid. When administered i.c.v., they induced convulsions with short onset latencies, suggesting that these compounds themselves have convulsant activities. In in vitro experiments using the whole cell clamp method, they suppressed gamma-aminobutyric acid (GABA)-induced Cl- current isolated on the dissociated mouse sensory neurons in dose-dependent manners through their actions as antagonists at GABAA receptors. The relative potency of the suppressive effects on GABA-induced Cl- current was compatible with that of the convulsant activities in mice. Furthermore, Ro15-1788 did not affect their convulsant activities. These results suggested that the amino-gamma-carbolines induced convulsions through their actions as antagonists at GABAA receptors and not through their actions as inverse agonists or antagonists at benzodiazepine receptors. Structure-activity relationships indicated that the 3-amino-group is important for the activities of amino-gamma-carbolines as GABAA receptor antagonists.

Animals↗

Evidence that chromium is an essential factor for biological activity of low-molecular-weight, chromium-binding substance.

Biologically active Low-molecular-weight, chromium-binding substance (LMCr) has been isolated from the liver of rabbits injected with potassium bicarbonate and cow's milk. This substance enhances glucose oxidation and lipogenesis from glucose in rat adipocytes [Yamamoto A. et al. (1987) Eur. J. Biochem. 165, 627-631; (1988) J. Nut. 118, 39-45]. LMCr was shown to lose its activity almost completely as an effectant of glucose metabolism when Cr was deleted under acidic conditions and separated from LMCr by EDTA-chelation and successive molecular-sieve chromatography. Reincorporation of Cr3+ into apo-LMCr resulted in 50-90% recovery of its original activity. These findings suggest that the biological activity of LMCr resides in Cr.

Adipose Tissue↗

Suppression of GABA-induced chloride current by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2).

The effect of a convulsive agent, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), on the GABA-induced chloride current (ICl) in dissociated mouse sensory neurons was investigated using the whole cell clamp method. Trp-P-2 reversibly suppressed the GABA-induced ICl in a dose-dependent manner. The IC50 for Trp-P-2 on the ICl evoked by 3 microM GABA was 11.1 microM. Ro15-1788 had no effect on the suppressive action of Trp-P-2. These results suggest that the observed effect of Trp-P-2 is mediated by its action as an antagonist at GABAA receptors.

Alanine↗

Exposure level monitor of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, a dietary carcinogen, in rabbits.

The present investigation describes a method for the detection of minute amounts of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), a carcinogenic tryptophan pyrolysate, bound to the hemoglobin of erythrocytes and plasma from rabbits dosed orally with the dietary carcinogen. The method consists of the acid-induced release of the dietary carcinogen adducts as the free carcinogen and their extraction with methylene chloride and subsequent quantitation by high-performance liquid chromatography (HPLC). With this method, Trp-P-1 levels in plasma, platelets, and red blood cells were monitored for 12 weeks to determine a suitable indicator for estimating the exposure levels of the dietary carcinogen. The results suggest that Trp-P-1 in red blood cells that bound covalently to the hemoglobin is the most suitable for monitoring the long-term exposure levels.

Administration, Oral↗

Exposure level monitor of a carcinogenic glutamic acid pyrolysis product in rabbits.

In order to determine a suitable indicator for estimating the exposure levels of the dietary carcinogen 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), a carcinogenic glutamic acid pyrolysis product, the levels of Glu-P-1 bound to blood components were monitored for 8 weeks by a high-performance liquid chromatography method after the dietary carcinogen was administered as single oral doses (0.2-50 mg) to rabbits. In all rabbits dosed with Glu-P-1, Glu-P-1 in erythrocytes was detectable even on day 42 after administration. Glu-P-1 in plasma disappeared faster than did Glu-P-1 in erythrocytes. Glu-P-1 levels in rabbit hemoglobin were linearly related to administered doses at all points of time investigated. The results suggest that Glu-P-1 covalently bound to hemoglobin is very suitable for monitoring long-term exposure levels.

Administration, Oral↗

Carcinogenic tryptophan pyrolysis products in airborne particles and rain water.

This is the first report that carcinogenic tryptophan pyrolysis products are present in airborne particles and rain water. The airborne particles were collected from August 1988 through October 1988 at 4 locations in Japan. The amounts of 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) in the air were 0.23 +/- 0.17 pg/m3 air (mean +/- SD, n = 18) and 0.16 +/- 0.15 pg/m3 air (n = 18), respectively. Moreover, these carcinogens were detected in rain water. These results indicate that Trp-P-1 and Trp-P-2 are ubiquitous environmental components.

Air Pollutants↗

Carcinogenic tryptophan pyrolysis products in human lens.

Mutagenic and 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 identified in human cataractous lenses, but not in young bovine lenses. The amounts of Trp-P-1 and Trp-P-2 in senile cataractous lenses were 156.34 +/- 35.63 fmol (mean +/- S.D., n = 10) and 128.27 +/- 40.45 fmol (n = 10), respectively, while those of Trp-P-1 and Trp-P-2 in diabetic cataractous lenses were 158.29 +/- 40.06 fmol (n = 10) and 150.34 +/- 23.77 fmol (n = 10), respectively. In both senile and diabetic cataractous lenses, the concentrations of Trp-P-1 and Trp-P-2 in the insoluble protein fraction (fmol mg-1 protein) were significantly higher than those in the water-soluble protein fraction. Moreover, proteinase-K treatment of lens protein before extraction with methylene chloride significantly increased the recoveries of Trp-P-1 and Trp-P-2. These results clearly indicate that carcinogenic tryptophan pyrolysis products, gamma-carboline derivatives, are present in human cataractous lenses and that these fluorescent carcinogens are significantly concentrated in the insoluble lens proteins.

Adult↗

Surgical treatment of metastatic tumors of the spine.

The goal of surgical treatment of metastatic spinal tumors is to maintain neurologic functioning without pain for the duration of the life expectancy. Of 28 patients in this series, 25 who had metastasis in the vertebral body underwent direct decompression by removal of the tumor, followed by vertebral reconstruction. A combined anterior or posterior instrumentation provided rigid spinal stability immediately after surgery. Three patients with involvement of the posterior part of the vertebra were treated by laminectomy for removal of the tumor, followed by posterior instrumentation. As a result, of nine patients who are alive with improved neurologic functions, seven have been ambulatory for an average duration of 13 months. Of 19 patients who have already died, recurrence of neurologic deficits was observed in five (26%), and 14 had no neurologic deterioration until they succumbed to the malignancy. Removal of the tumor and reconstructive surgery may be expected to produce satisfactory results.

Adult↗

Experimental analysis of the spinal cord compressed by spinal metastasis.

The purpose of the present study of experimental spinal metastasis, developed in rats by inoculation of tumor cells through the spinous process, was to find the factor that causes the initial damage to the cord in this disorder. In the early stage of paralysis, the degenerated posterior funiculus originated from a small hemorrhagic area in the posterior column of the involved cord. Using the scanning electron microscope, the hemorrhage was found to be from the intrinsic vein, resulting from the disturbance of venous drainage in the compressed portion. In the early stage of compression, extravasation of horseradish peroxidase was observed in the white matter, but histologic degeneration was not. A hemorrhage existed wherever degeneration of the funiculus was observed. Therefore, the trigger to induce the initial damage on the cord in spinal metastasis was not likely to be vasogenic edema, but instead the intrinsic venous hemorrhage.

Angiography↗

A novel method for removal of human immunodeficiency virus: filtration with porous polymeric membranes.

We propose a new method to rid solutions of a virus by using a novel regenerated multilayered structured cellulose membrane (BMM). When the filtrate of human immunodeficiency virus (HIV) preparation was obtained through BMM it showed no infectivity. Electron microscopic observation revealed that HIV was completely caught by the multilayers of the BMM. Conveniently, BMM was seldomly found to adsorb protein molecules and also to have a high filtration rate. These characteristics may have a use in the removal of other variously sized pathogenic agents from plasma.

Cells, Cultured↗

The decomposition and aggregation of rat lens protein induced by selenite in vitro and in vivo.

A single subcutaneous injection of sodium selenite at the dose of 20 mumol/kg body weight induced bilateral nuclear cataracts in suckling rats. This selenite-induced cataract incidence can be increased by pretreating animals with a glutathione synthesis inhibitor. Sodium dodecyl sulfate polyacrylamide electrophoresis of urea-soluble proteins from selenite-induced cataractous lenses showed the appearance of high molecular weight aggregates and decomposed products of lens proteins. These products were found in association with the emergence of a 45 K band. Incubation of water-soluble lens proteins with selenite in vitro produced changes similar to those demonstrated in selenite-induced cataractous lenses. Furthermore, selenite induced the gradual development of opalescence and the oxidation of sulfhydryl in the lens protein solution. Therefore, we presume that the oxidation of lens protein sulfhydryl by selenite is associated with both aggregate formation and the decomposition of lens proteins, and that these changes may provide a partial explanation for the mechanism of selenite cataract.

Animals↗

[Present and future of carcinogenic tryptophan pyrolysis products in the environment].

Food has been considered an important factor for the genesis of cancer in man, as important as cigarette smoking. Diet influences the incidence of human cancer in many ways, directly and indirectly. Various kinds of carcinogens such as polynuclear aromatic hydrocarbons, N-nitro compounds and mycotoxins have been reported to be present in various foods. During the last decade, a new series of heterocyclic amines has been isolated as potent mutagens and later shown to be potent carcinogens in animals. Among them, carcinogenic tryptophan pyrolysates have been investigated from various points of view and useful pieces of information about them have been collected. Now, it is a matter of urgency to evaluate the effects of these carcinogens on humans. From this aspect, this review describes the information about carcinogenic tryptophan pyrolysates which has been collected and also future problems, especially those the hygienist will have to solve.

Carbolines↗

[Study on the repeated oral administration method in infant rats].

The purpose of this study was to establish a new technique for repeated oral administration to infant rats. To determine the maximum volume which could be administered to infant rats the following amounts of the Chinese ink were given by metal gastric zonde for mice: 0.01, 0.04 and 0.08ml/g B. W. General conditions and the arrival distance of the Chinese ink in the gastro-intestinal tract were also observed in infant rats. The best way of administration to infant rats was decided as follows: infant rats were isolated from the dums for one hour before administration and held tenderly by their neck to sustain their mouth upward, then a metal gastric zonde for mice 2 cm long was inserted to their mouth and drug solution was injected slowly. From the observation of general conditions and pathological examination, the maximum volumes for single or repeated administration were considered to be 0.04ml/g B. W. and 0.01 ml/g B. W. respectively. Daily oral administration of 0.1ml/g B. W. of distilled water, 1% CMC solution or 1% tragacantha gum suspension for 44 days caused no effects in infant rats when administration was begun 4 days after birth. These results show that the new method for administration to infant rats is useful to evaluate the toxicity or pharmacological activity of drugs.

Administration, Oral↗

Preliminary dose finding study for subacute toxicological study of pravastatin sodium in monkeys.

Pravastatin sodium was orally administered to cynomolgus monkeys at dosage levels of 50, 200 and 800 mg/kg/day for 7 successive days. Excretion of diarrhea and/or loose stool were observed in the more than 50 mg/kg dose group, but the changes are quite mild. Animals of the 800 mg/kg dose group showed vomiting, diarrhea and/or excretion of soft stool and reduction of cholesterol content in serum. In conclusion, it is estimated that the no effective level is less than 200 mg/kg because no abnormalities were observed except for only very slight excretions of diarrhea and/or loose stool, and that the effective dose is 800 mg/kg in which vomiting was observed.

Administration, Oral↗

Subacute toxicological study in monkeys treated orally with pravastatin sodium for 5 weeks.

Pravastatin sodium was administered orally to cynomolgus monkeys at dosage levels of 50, 100, 200 and 400 mg/kg/day for 5 successive weeks. Five animals of 200 mg/kg and 400 mg/kg dose groups were sacrificed during the study period, because these animals deteriorated in general condition and/or showed remarkable changes in serum biochemical examination. Pathological examination revealed hepatic and/or renal disturbance in these animals. These changes are thought to be the cause of deterioration of general condition or changes in serum biochemical examination. All other animals were terminated at the end of the study period. In the animals of the 100 mg/kg dose group, only one animal showed hepatic and renal disorder similar in nature to the changes in the animals sacrificed during the study period. No animals in the 50 mg/kg dose group showed toxic findings in any examination.

Administration, Oral↗