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Biomedical subjects

M Satake

Publications and source records attributed to M Satake.

At least 181 records · Page 10Linked to original sources

[Fatal ichthyosarcotoxism after eating shark meat. Implications of two new marine toxins].

A fish poisoning involving 188 hospitalizations occurred in November 1993, in Manakara, a middle-sized town on the south-east coast of Madagascar, following the ingestion of shark. A single shark was involved in this poisoning and was identified as Carcharinus leucas. There was no unusual characteristic of this shark or its meat. The attack rate was about 100%. First clinical signs appeared within five to ten hours after ingestion. The patients presented neurological symptoms almost exclusively, the most prominent being a constant, severe ataxia. Gastrointestinal troubles, like diarrhoea and vomiting were rare. The overall case-fatality ratio was close to 30% among the 200 poisoned inhabitants. Search for similar poisoning previously reported in this area was negative, and fishermen in Manakara usually eat that kind of shark without mistrust. Bacteriological and chemical origins were eliminated. Two liposoluble toxins were isolated from the shark liver and tentatively named carchatoxin-A and -B respectively. They were distinct from ciguatoxin in chromatographic properties.

Adult↗

Xenorecognition and xenoimmunity.

Human T lymphocytes can respond against pig stimulator cells according to a direct pathway of activation, indicating that no major differences exist between human T cell mediated alloresponses and xenospecific responses against pig stimulator cells in vitro. However, even if pig PBMC can activate T cells directly, it is believed that porcine islet cell clusters are incapable of activating cellular immunity directly in vivo, since ICC xenotransplants are thought to lack antigen-presenting cells. Therefore, specifically immunized T lymphocytes are not likely to be able to interact directly with xenogeneic target cells. We propose that xenogeneic transplants lacking antigen-presenting cells are subjected to antibody-dependent cell-mediated rejection mechanisms. The humoral xenoimmune response against pig antigens was swift and strong in all transplanted patients with peak antibody reactivities recorded on days 30-40. Titer increases in all lg-classes and subclasses were found. The humoral immune response was mainly, if not exclusively, directed against alpha-linked galactose-containing sugar residues, present on many different glycoproteins, including SLA class I antigens. There were no signs of de novo stimulation of B cell clones following xenoimmunization, rather an increased reactivity in cells producing xenospecific antibodies as part of the normal background of antibody production in healthy individuals. The findings form part of a basis for understanding xenoimmune mechanisms in man. The relatively homogeneous antibody specificities found both in normal and in immune patients are promising for future xenotransplantation using pig organs in man.

Animals↗

PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene.

cDNAs representing the alpha subunit of polyomavirus enhancer binding protein 2 (PEBP2; also called PEA2) were isolated. The products of the cDNAs are highly homologous to that of Drosophila segmentation gene runt (run) for an N-proximal 128-amino acid region showing 66% identity. The run homology region encompasses the domain capable of binding to a specific nucleotide sequence motif and of dimerizing with the companion beta subunit. The human AML1 gene related to t(8;21) acute myeloid leukemia also had a run homology region. Together with the beta subunit, which increases the affinity of the alpha subunit to DNA without binding to DNA by itself, PEBP2 represents a newly discovered family of transcription factor. The major species of PEBP2 alpha mRNA was expressed in T-cell lines but not in B-cell lines tested. Evidence indicated that PEBP2 functions as a transcriptional activator and is involved in regulation of T-cell-specific gene expression.

Amino Acid Sequence↗

Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha.

Polyomavirus enhancer binding protein, PEBP2 (PEA2), is a heterodimer of two distinct subunits, alpha and beta, of which the former directly binds to DNA and the latter acts auxiliary to enhance the DNA binding. Recent cloning studies has revealed that the alpha subunit is homologous to the products of the Drosophila segmentation gene runt and the human AML1 gene, and that it functions as a major regulator for the T cell-specific gene expression. We have currently cloned cDNAs for the beta subunit. The isolated cDNAs contain three isoforms that are presumed to arise from alternative RNA splicing and encode polypeptides consisting of 187, 182, and 155 amino acids, respectively. These polypeptides neither show any significant homology with known other proteins including the alpha subunit nor have any known DNA-binding and dimerization domains. Thus, PEBP2, as the complex of these subunits, is thought to constitute an entirely novel category of heteromeric transcriptional regulator together with the Runt and AML1 proteins. Gel retardation assays of the cDNA-encoded proteins produced in an in vitro translation system or in Escherichia coli demonstrated that the larger two beta isoforms, but not the smallest one, can dimerize with the alpha subunit. Furthermore, this heterodimerization was shown to cause a marked increase in the intrinsic DNA binding affinity of the alpha subunit.

3T3 Cells↗

Transacting activities of the E7 genes of several types of human papillomavirus.

In accordance with previous reports by others, the E7 gene of human papillomavirus (HPV) 16, considered to be etiologically associated with cervical cancer, transactivated the E2 promoter of adenovirus. This promoter, however, was equally stimulated by the E7 gene of HPV1, a skin type HPV never associated with human malignancy. A variety of promoters were tested to see the effect of the E7 genes of low-risk and high-risk type HPVs. The result indicated that there was no obvious relationship in the levels of transactivation or transrepression by the E7 gene between low-risk and high-risk types. It has been suggested that the binding of the E7 protein to the product of retinoblastoma susceptibility gene (pRb) is the underlying mechanism by which the E7 protein transactivates the E2 promoter. Therefore, the association of the E7 protein and pRb alone did not seem to fully explain the mechanism by which this protein participates in the activation of transcription and induction of human malignancies.

Adenoviridae↗

A case of steroid-responsive organizing pneumonia in a patient with rheumatoid arthritis showing migratory infiltration and normal glucose levels in pleural effusions.

A 59-year-old Japanese man with RA was referred to us with arthralgia and pulmonary infiltration. Chest roentgenogram showed migratory infiltration and pleural effusion, the glucose levels of the pleural fluid were not reduced. Transbronchial lung biopsy showed granulation tissue plugging the alveolar ducts, indicating organizing pneumonia and interstitial inflammation. These pathological findings were identical with those for cryptogenic organizing pneumonitis (COP). There was a good clinical and roentgenographic response and the pleural effusion responded well to corticosteroids. The characteristic migratory infiltration in rheumatoid lung disease responds well to corticosteroids.

Arthritis, Rheumatoid↗

Comparative study on the accelerative effect of "koushikon" and "nanshikon" and their constituents on proliferation of granuloma tissue in rats.

This study was carried out to compare the accelerative effect in ether extracts of "Koushikon" and "Nanshikon" on proliferation of granuloma tissue in rats, and to elucidate this effect on optical isomer of naphthoquinone derivatives in those extracts. The content of total naphthoquinone derivatives in the ether extracts of Koushikon and Nanshikon were found to be 56.1% and 25.4%. Among naphthoquinone derivatives, Koushikon contained mostly acetyl derivative and Nanshikon mostly teracryl derivative. The percentage of R-type (shikonin-type) in total naphthoquinone derivatives of the extracts was 85.5% and 3.8%. Each ether extract showed a dose-dependent acceleration on the cotton pellet-induced granuloma formation. Comparison with corresponding doses containing the same quantity of naphthoquinone derivatives showed the accelerative potency of ether extracts of Koushikon and Nanshikon to be about the same. The result suggests that the accelerative effect on proliferation of granuloma tissue depends primarily on the total content of naphthoquinone derivatives, and not on the ratio of the optically active isomers.

Animals↗

Ascaridole as a pharmacologically active principle of "Paico," a medicinal Peruvian plant.

"Paico," Chenopodium ambrosioides L., is a traditional Peruvian medicine which is considered to be nervine, antirheumatic, anthelmintic, etc. An attempt was made to isolate the component having sedative and/or analgesic properties from "Paico" and "Aritasou" (the Japanese name for C. ambrosioides). Ascaridole was identified as the active principle in both materials.

Analgesics↗

Analgesic component of Notopterygium incisum Ting.

Notopterol was identified as the analgesic component of Notopterygium incisum TING by using the acetic acid-induced writhing method. Notopterol also indicated an anti-inflammatory activity by its inhibitory effect in the vascular permeability test. The intensive prolongation of pentobarbital-induced hypnosis was possibly caused by its inhibitory effect on the drug metabolism in liver. Pharmacological differences between the analgesic components of N. incisum, Aralia cordata and Angelica pubescens were also discussed.

Animals↗

[Comparative studies on concentration of berberine in plasma after oral administration of coptidis rhizoma extract, its cultured cells extract, and combined use of these extracts and glycyrrhizae radix extract in rats].

The present study was carried out to evaluate the bioequivalence between Coptidis Rhizoma and the cultured cells of Coptis japonica Makino var. dissecta Nakai to compare the concentration of berberine in the rat plasma after oral administration of both aqueous extracts. The concentration of berberine in the plasma after oral administration of both extracts was determined by HPLC. It was found that the values of time required for the maximum concentration (Tmax), the maximum concentration (Cmax) and the area under the plasma-time curve (AUC24h) of berberine in the rat plasma after oral administration of both extracts were about the same. It was also found that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts and an aqueous extract of Glycyrrhizae Radix were about the same as that of individual administration of both extracts. From these results, to evaluate the bioequivalence between Coptidis Rhizoma and cultured cells, it is important that the values of Tmax, Cmax and AUC24h of berberine after oral administration of both extracts are not different, and about the same values of berberine by the combined use of both extracts and the aqueous extract of other crude drugs are required.

Administration, Oral↗

Impact of stress on serum gastrin in Zollinger-Ellison syndrome.

We report an impressive case with Zollinger-Ellison syndrome (ZES), in which stress-induced sympathetic discharge influenced serum gastrin. Our patient was a 35-yr-old female who complained of frequent and massive vomiting (more than 4000 ml of gastric juice) which was aggravated especially by psychosocial stress. Basal hypergastrinemia (1900 pg/ml) was found after the admission. The most striking finding was that laboratory stress dramatically increased serum gastrin (from 1900 to 5400 pg/ml) and plasma noradrenaline (from 180 to 1130 pg/ml). Mental arithmetic stress further enhanced hypergastrinemia (5800 pg/ml) with a concomitant increase in plasma noradrenaline (1240 pg/ml). Neostigmine (10 micrograms/kg im) also increased serum gastrin up to 6100 pg/ml but propranolol (40 micrograms/kg i.v.) reduced these elevations (noradrenaline: 990 pg/ml, gastrin: 5000 pg/ml). In this case, the effect of stress on serum gastrin mimicked the effect of catecholamine infusion in ZES. These findings suggest that psychological stress induces serum gastrin secretion via beta-adrenoceptor with exacerbation of symptoms in some cases with ZES.

Adult↗

Treatment of hepatocellular carcinoma by intraarterial injection of adriamycin/mitomycin C oil suspension (ADMOS) alone or combined with cis-diaminodichloroplatinum (CDDP).

We evaluated the effects of intraarterial injection of Adriamycin/Mitomycin C oil (Lipiodol) suspension (ADMOS) alone and ADMOS+cis-diaminodichloroplatinum (CDDP) in 135 patients with hepatocellular carcinoma (HCC). A total of 59 patients received ADMOS alone and 76 patients received ADMOS+CDDP (ADMOS/CDDP). Tumor size was reduced by over 25% in 13 (34%) of the evaluable 38 patients in the ADMOS-alone group and in 39 (51%) of the 76 evaluable patients in the ADMOS/CDDP group. Serum alpha-fetoprotein (AFP) levels decreased by more than 50% in 10 (59%) of 17 ADMOS-alone patients and in 23 (70%) of 33 ADMOS/CDDP patients whose pretreatment AFP levels were above 0.2 mg/l. The overall one- and 2-year survival rates were 68% and 41%, respectively. No severe complications and no significant changes in laboratory values were observed, except for one patient in the ADMOS/CDDP group who developed a liver abscess. Although the tumor response was significantly better in patients treated by ADMOS/CDDP than in those treated by ADMOS-alone (p < 0.05), there was no significant difference in the survival rates between the 2 groups. The intraarterial injection of ADMOS and CDDP was concluded to be effective in treating HCC judging by tumor response.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of lidocaine metabolite (monoethylglycinexylidide) as a liver function test].

In order to determine whether or not the lidocaine metabolism, monoethylglycinexylidide (MEGX) formation, could be used as a liver function test, we measured the serum levels of MEGX in 38 patients. There were significant correlations between values of MEGX (MEGX15, MEGX30, AUC15-30, AUC0-180) and conventional liver function tests (ICG R15, AT III, T. Bil). It appeared that value of MEGX 30 had maximum factor loading on conventional liver function tests by using principal component analysis. The advantage of adapting the MEGX formation as a liver function test of drug metabolism is simplicity of the method. MEGX formation could be useful index of the total liver function.

Evaluation Studies as Topic↗

Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1.

Breakpoints of the t(8;21) chromosome translocation in acute myeloid leukemia are clustered within the human gene, AML1, located on chromosome 21 [Miyoshi, H., Shimizu, K., Maseki, N., Kaneko, Y. & Ohki, M. (1991). Proc. Natl. Acad. Sci. USA, 88, 10431-10434]. The product of AML1 has a region about 130 amino acids long that is highly homologous to the Drosophila segmentation gene runt (runt homology region). The cDNA isolated from mouse fibroblasts encoding the alpha-subunit of polyomavirus enhancer binding protein 2 (PEBP2/PEA2) revealed that it also has a runt homology region (E. Ogawa et al., submitted). In this study, a different cDNA clone presumed to represent the mouse homolog of human AML1 (PEBP2 alpha B) was isolated from a cDNA library derived from B cells. The deduced amino acid sequence of PEBP2 alpha B is 99% identical to that of AML1 for the first 241 residues, including the runt homology region, though their sequences diverge thereafter. On the other hand, PEBP2 alpha B and PEBP2 alpha share only 92% and 82% homologies at the amino acid and nucleotide levels respectively, even for the runt homology region, indicating that these proteins are encoded by distinct genes. While PEBP2 alpha is highly expressed in T-cell lines but not in most of the B-cell lines and functions as an activator of T-cell-specific genes, PEBP2 alpha B is expressed in both types of cells. A possible functional relationship between PEBP2 alpha and PEBP2 alpha B is discussed in relation to leukemogenic potential of AML1.

3T3 Cells↗