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Biomedical subjects

S Manabe

Publications and source records attributed to S Manabe.

At least 73 records · Page 4Linked to original sources
PubMed1991

Zone-specific hepatotoxicity of gossypol in perfused rat liver.

Gossypol selectively damages the periportal region of lobules in perfused rat liver, while retrograde perfusion caused pericentral liver damage. Moreover, the addition of 0.4% bovine serum albumin(BSA) to the perfusate completely prevented the toxic effect of gossypol on hepatocytes, decreasing the absorption of gossypol by the liver. This study indicates that the damage caused by gossypol depends upon the direction of exposure and can be protected against by its binding to BSA.

Animals↗
PubMed1991

The particle size of hepatitis C virus estimated by filtration through microporous regenerated cellulose fibre.

To estimate the particle size of hepatitis C virus (HCV), a major causative agent of post-transfusion non-A, non-B hepatitis, we filtered plasma or serum samples through microporous cellulose fibres with different pore sizes. The amount of HCV particles in samples before and after filtration was determined by a quantitative reverse transcriptase polymerase chain reaction (PCR) method. Since there is no quantitative biological assay for HCV, except for that in chimpanzees, the HCV titre obtained from the PCR method was used in an equation constructed previously for application to filtration experiments with a flavivirus which is distantly related to HCV. The particle was estimated to be between 30 and 38 nm in diameter, although the possibility remained that larger HCV particles or HCV aggregates with a diameter of more than 39 nm might exist. Double-step filtration through microporous cellulose fibres with a pore size of 35 nm reduced the HCV content to below levels detectable by our PCR method, indicating that it is possible to eliminate HCV particles by simple filtration techniques.

Base Sequence↗
PubMed1991

Structure and organization of the hepatitis C virus genome isolated from human carriers.

Hepatitis C virus (HCV) is a major causative agent of posttransfusion non-A, non-B hepatitis, which often develops into malignant chronic diseases, including liver cirrhosis and hepatocellular carcinoma. We have cloned from human carriers overlapping cDNAs (9,416 bp) covering the entire coding region of the HCV genome. The latter encodes a 3,010-amino-acid polyprotein. In addition, there are 332 and 54 bases of 5' and 3' noncoding sequences, respectively. Our HCV strain has a 77% nucleic acid identity to the HCV strain cloned by workers at Chiron Corporation. The hydrophobicity profile of the putative polyprotein is similar to those of flaviviruses, but it has limited amino acid homology to polyproteins of flaviviruses and other viruses, indicating that HCV is at most distantly related to flaviviruses.

Amino Acid Sequence↗
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

An attempt to prepare hepatitis B virus (HBV)-free plasma by ultrafiltration using microporous regenerated cellulose hollow fiber.

Hepatitis B virus (HBV) can be effectively removed from HBV-positive plasma by filtration with a Bemberg Microporous Membrane (BMM) with a pore size of 30 nm or less, however considerable amounts of macromolecular IgM and Factor VIII are trapped in the BMM. We report that HBV-free plasma with adequate amounts of all of the plasma proteins can be obtained by double filtration with a BMM with a port size of 50 nm. Thus it may be possible to remove HBV or other transfusion-associated viruses from plasma by BMM filtration with good recovery of all of the plasma components.

Blood Proteins↗
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↗