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S Manabe

Publications and source records attributed to S Manabe.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Carcinogenic heterocyclic amines in the environment].

The purpose of this report is to summarize data on carcinogenic heterocyclic amines mainly from the aspect of environmental medicine. Since 1977, a new series of heterocyclic amines has been isolated as potent mutagens and they have been shown to be carcinogenic to experimental animals. Among these carcinogens, carcinogenic amino-alpha-carbolines and amino-gamma-carbolines are widely distributed in such components of the environment as airborne particles, rain water, cigarette smoke, diesel exhaust particles and cooked foods. Moreover, most carcinogenic heterocyclic amines are reported to be present in cigarette smoke. These facts suggest that carcinogenic heterocyclic amines are likely to be ubiquitous environmental pollutants. These results also support the hypothesis that carcinogenic heterocyclic amines may be formed through combustion of various materials such as food, grass and petroleum.

Amines↗
PubMed1991

Urinary excretion levels of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives in humans.

UNLABELLED: The carcinogenic glutamic acid pyrolysis products 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido [1, 2-a: 3', 2'-d] imidazole (Glu-P-2), and their N-acetyl derivatives were measured in 24-h urine of individual subjects by high-performance liquid chromatography. These compounds were detected in all urine samples analyzed, although the contents varied widely among subjects. The mean levels of Glu-P-1, N-acetyl-Glu-P-1, Glu-P-2 and N-acetyl-Glu-P-2 in 24-h urine were 0.53, 0.41, 2.12 and 4.60 pmol, respectively. In vitro experiments revealed N-acetyltransferase activity with Glu-P-1 and Glu-P-2 in the cytosolic fractions from rat kidneys and human autopsy kidney specimens as well as those from liver specimens, suggesting that extrahepatic tissues may also play significant roles in the N-acetylation of these carcinogens. These results show that Glu-P-1 and Glu-P-2, after being partially N-acetylated in metabolic organs such as liver and kidney, are excreted into urine together with their N-acetyl derivatives. It is suggested that daily excretion of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives into urine can be a suitable biological monitor for exposure to these carcinogens. ABBREVIATIONS: Glu-P-1, 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; Glu-P-2, 2-aminodipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-1, 2-acetylamino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-2, 2-acetylaminodipyrido[1,2- a:3', 2'-d]imidazole; HPLC, high-performance liquid chromatography.

Acetylation↗
PubMed1991

Expression of the hepatitis B surface antigen gene containing the preS2 region in Saccharomyces cerevisiae.

We constructed a plasmid, pBH103-ME5, in which the region encoding the 10 preS2 amino acid residues and the S domain of the hepatitis B surface antigen (HBsAg) were regulated by the promoter of the yeast repressible acid phosphatase gene. Saccharomyces cerevisiae carrying pBH103-ME5 produced the HBs antigen (yHBsAg), when it was cultured in a medium containing a low concentration of phosphate. The antigen was purified to homogeneity. Its molecular weight was determined by Western blotting to be 24,000, and its amino acid composition agreed well with that deduced from the nucleotide sequence. The C-terminal amino acid sequence of yHBsAg was exactly the same as that predicted from the nucleotide sequence, while the N-terminal amino acid acetylserine, which was followed by 8 amino acid residues coded by the preS2 region. These results indicate that the recombinant yeast produced a single polypeptide consisting of the preS2 region and the subsequent S domain after being processed at the N-terminus.

Amino Acid Sequence↗
PubMed1991

Carcinogenic tryptophan pyrolysis products in the environment.

The purpose of this study is to evaluate the risk of carcinogenic tryptophan pyrolysis products to human health. During the last decade, a new series of heterocyclic amines has been isolated as potent mutagens and later shown to be potent carcinogens in experimental animals. Among them, 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), carcinogenic tryptophan pyrolysis products, have been investigated from various points of view and useful pieces of information about them have been collected. These carcinogens are widely distributed in the environment such as airborne particles, rain water, cigarette smoke and cooked foods, and they possess various pharmacotoxicological activities such as convulsant activities and potent inhibitory effects on platelet function and dopamine metabolism. Recent investigations revealed that these compounds are present in human samples such as plasma, urine and bile, indicating that humans are actually exposed to these compound. It is a matter of urgency to establish a suitable method for monitoring the exposure levels of these compounds to humans.

Animals↗
PubMed1991

[Dumbbell type tumor of a nerve root treated surgically by vertical curvilinear approach].

A 42-year-old man was admitted for further examination of an abnormal shadow on the posterior mediastinum which was incidentally detected by a routine chest X-ray. Myelography followed by computerized tomographic scanning (CT) revealed that a dumbbell shaped tumor had developed in the paravertebral area adjacent to the vertebral canal through an intervertebral foramen. A vertical curvilinear incision centered at T-6 was made with the patient in a prone position. Total laminectomy or T-5 and T-6 and resection of the left 6th rib provided sufficiently wide exposure for a one-stage resection of the tumor. The dumbbell shaped tumor originated from the root of 6th spinal nerve but did not extend to the spinal cord. The extirpated tumor was diagnosed histologically as schwannoma. Because tumor location had been determined preoperatively by CT scanning after myelography, it was possible to perform complete extirpation of the tumor while avoiding the complications of laminectomy and unnecessary thoracotomy.

Adult↗
PubMed1990

Simultaneous determination of amino-alpha-carbolines and amino-gamma-carbolines in cigarette smoke condensate by high-performance liquid chromatography.

A method for the simultaneous detection of amino-alpha-carbolines (2-amino-alpha-carboline and 2-amino-3-methyl-alpha-carboline) and amino-gamma-carbolines (3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole and 3-amino-1-methyl-5H-pyrido [4,3-b]indole) by high-performance liquid chromatography has been developed. It consists of a three-step purification using three different columns with fluorometric detection. With this method, we have demonstrated that both amino-alpha-carbolines and amino-gamma-carbolines are present in cigarette smoke condensate. The method may be useful for detecting these carcinogens in various materials.

Carbolines↗
PubMed1990

Identification of carcinogenic tryptophan pyrolysis products in human bile by high-performance liquid chromatography.

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 demonstrated to be present in human bile through use of a high-performance liquid chromatography (HPLC) method. The method consists of the acid-induced release of the carcinogens from bile components and their extraction with methylene chloride and subsequent quantification by HPLC. In seven subjects who had received catheterization of the bile duct and external biliarydrainage, the average amounts of Trp-P-1 and Trp-P-2 excreted daily in the bile were 408 fmol/day (n = 7) and 864 fmol/day (n = 7), respectively. In one subject, furthermore, significant daily changes of these carcinogen levels in bile and plasma were confirmed during 2 weeks of observation. These results indicate that one of the excretory pathways of these carcinogens is via bile. Our data also may suggest that Trp-P-1 and Trp-P-2 are derived from everyday foods.

Bile↗
PubMed1990

Correlation between lipid peroxidation and morphological manifestation of paraquat-induced lung injury in rats.

Biochemical and morphological studies of rat lung were performed to determine the role of lipid peroxidation in the in vivo lung toxicity of paraquat. Two injections of 20 mg/kg paraquate were administered intraperitoneally every other day. While notable epithelial damage in the lungs was observed on the day after the second paraquat injection and progressed through the 5th day, the concentration of lipid peroxides in the rat lungs did not increase by the 3rd day after the injection. The lipid peroxide concentrations increased after the 5th day post-injection, and reached the maximum concentrations on the 7th day, when the damaged alveolar surface had been mostly repaired by regenerative pneumocytes. On the other hand, the delayed increase of lung lipid peroxides in paraquat-treated rats paralleled the increased number of macrophages in the lung, which reached maximum numbers on the 7th day. Glutathione peroxidase activity in the lungs also increased with a similar time course. Macrophages from the lungs contained a large amount of engulfed degradation products and cellular debris, and immunohistochemical study showed high glutathione peroxidase content on the 5th and 7th days. These results suggest that lipid peroxidation is a relatively late event in the in vivo paraquat-treated lung and that the delayed increase of lipid peroxides in the lungs occurs from the phagocytic activities of macrophages rather than from toxic cell injury.

Animals↗
PubMed1990

Detection of carcinogenic glutamic acid pyrolysis products in cigarette smoke condensate.

Carcinogenic glutamic acid pyrolysis products were measured in condensate of cigarette mainstream smoke by HPLC. These carcinogens were found to be present in all brands of filter-tipped cigarette analyzed. The mean levels of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-aminodipyridol[1,2-a:3',2'-d]imidazole in the cigarette mainstream smoke were 0.66 and 0.63 ng/cig respectively.

Carcinogens↗
PubMed1990

Analysis of the molecular requirements for T cell recognition and activation by using Ia-containing lipid vesicles and stopped-flow fluorometry.

Using Ia antigen-containing lipid vesicles, we investigated by stopped-flow fluorometry the requirements for helper T cell recognition and activation. When azobenzenearsonate-L-tyrosine (ABA-L-Tyr)-specific, I-Ak-restricted helper T cell hybridomas 2-45-12 were mixed with ABA-L-Tyr and purified I-Ak molecules on lipid vesicles, an increase of intercellular calcium ion concentration ([Ca2+]i) in the T cells were detected within 1-2s. The average increases of [Ca2+]i were not much different when the lipid vesicles were composed of dimyristoylphosphatidylcholine or of egg phosphatidylcholine, but they were dependent on the density of I-Ak molecules on the liposomes. The increase of [Ca2+]i was inhibited in the presence of anti-I-Ak monoclonal antibody 10.2.16, but not by the addition of anti-L3T4 monoclonal antibody GK1.5. However, the addition of anti-L3T4 antibody during the first 3 h of cultivation completely inhibited the T cell activation [interleukin (IL-2) production]. In our experimental system, IL-2 production was observed either when L3T4-positive T cell hybridomas 2-45-12 were stimulated with ABA-L-Tyr and Ia molecules on the vesicles in the presence of phorbol 12-myristate 13-acetate, or when L3T4-negative T cell hybridomas 3H60.12 were incubated with ABA-L-Tyr and Ia molecules on the planar membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Surgical treatment of metastatic spinal malignancies].

The goal of surgical treatment of metastatic tumors of the spine is maintaining the relief of pain and/or neurologic symptoms for as long as possible after surgery. For the quality of life, thirty-five patients were surgically treated. By preoperative analyses, tumor invasion was divided into 3 types as follows; Type 1: involvement of vertebral body, Type 2: involvement of posterior column, Type 3: involvement of anterior and posterior column. Of 35 patients, 31 were in Type 1 or 3, who underwent anterior and/or posterior direct decompression by removal of the tumor, followed by vertebral reconstruction. Posterior surgery was performed on the remaining 4 patients in Type 2, resulting in complete decompression. A combined anterior or posterior instrumentation with anterior reconstruction for the involved vertebral body in Type 1 and 3 provided rigid spinal stability immediately after surgery. Neurologic improvement was evaluated by Frankel's classification. As a result, 4 patients who are alive have been ambulatory for an average duration of 26.3 months. Thirty-one, who survived for an average duration of 10 months, had no neurologic deterioration in an average duration of 8.4 months. Removal of the tumor and reconstructive surgery combined with rigid spinal instrumentation may provide satisfactory results.

Adult↗
PubMed1990

[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↗
PubMed1990

[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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗