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Biomedical subjects

T Noguchi

Publications and source records attributed to T Noguchi.

At least 469 records · Page 26Linked to original sources

Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains.

PTP1C is a non-transmembrane protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. Insulin stimulated the tyrosine phosphorylation of PTP1C in human 1M-9 lymphoblast cells, in rat H35 hepatoma cells and in Chinese hamster ovary cells over-expressing both insulin receptors and PTP1C. Insulin also stimulated the tyrosine phosphorylation of a mutant PTP1C lacking SH2 domains in Chinese hamster ovary cells, suggesting that the SH2 domains are not required for insulin-stimulated tyrosine phosphorylation of PTP1C. The insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1C in a cell-free system. Peptide mapping of phosphorylated PTP1C showed that Tyr538 in the C-terminal region was phosphorylated in response to insulin. The tyrosine phosphorylation of PTP1C by the insulin receptor kinase increased phosphatase activity. Furthermore, PTP1C was shown to bind to autophosphorylated insulin receptors through its C-terminal region, but PTP1C did not bind to unphosphorylated receptors. These results suggest that PTP1C is a target protein for the insulin receptor tyrosine kinase and that the C-terminal region of PTP1C may function both in the regulation of phosphatase activity and in the association of PTP1C with autophosphorylated insulin receptors.

Amino Acid Sequence↗

Amphibian allantoinase. Molecular cloning, tissue distribution, and functional expression.

The chain of enzymes necessary to convert uric acid to its metabolic products urea and glyoxylic acid in vertebrates is truncated through the successive loss of allantoicase, allantoinase, and urate oxidase during phylogenetic evolution. Previous studies have assigned the localization of both urate oxidase and allantinase to the peroxisome in the amphibian liver. This study reports the cloning of a cDNA encoding bullfrog (Rana catesbeiana) allantoinase, an enzyme that converts allantoin to allantoic acid. The cDNA is 2112 base pairs in length containing a 1449-base pair open reading frame which corresponds to a 483-residue protein (53,296 Da). Structural analysis of the deduced protein suggested two potential transmembrane segments and the presence of a putative mitochondrial localization sequence in the amino terminus. Immunocytochemical analysis revealed that allantoinase is localized to mitochondria and not to peroxisomes. On Northern blotting, a single mRNA species was detected in the liver and kidney of frog but not in other tissues; this distribution was confirmed by immunoblotting. The hepatic- and renal-specific expression of allantoinase coincides with the distribution of urate oxidase in these tissues in the frog. The allantoinase expressed in Saccharomyces cerevisiae and in Spodoptera frugiperda (Sf9) insect cells exhibits catalytic activity and is antigenically identical to the native frog enzyme.

Amidohydrolases↗

Molecular cloning of human hippocalcin cDNA and chromosomal mapping of its gene.

We have isolated a cDNA clone encoding human hippocalcin from a human hippocampus cDNA library. This clone (hHLP1) consists of 840 nucleotides, including the entire open reading frame of 582 nucleotides, 10 nucleotides of the 5' leader and 248 nucleotides of the 3' noncoding regions. Comparison of the human hippocalcin sequence with the corresponding rat sequence revealed an amino acid identity of 100% and nucleotide identity of 92%. Northern blot analysis showed that a single transcript at a position corresponding to 2.0 kb was detected only in the brain. The human hippocalcin gene was mapped to chromosome 1 by amplification of human hippocalcin-specific DNA fragment on DNA from human-rodent somatic cell hybrids by using the polymerase chain reaction.

Amino Acid Sequence↗

Transcriptional regulatory regions for expression of the rat pyruvate kinase M gene.

To study the regulatory mechanism of pyruvate kinase M gene transcription, we analyzed its chromatin structure and cis-acting DNA regions. Two DNase-I-hypersensitive sites were detected in dRLh-84 hepatoma cells, but not in hepatocytes, which coincides with expression of the M gene in the two types of cells. These sites, designated HS2 and HS1, were located around the major transcription start site and about 2.9 kb downstream from this site, respectively. A transient chloramphenicol acetyltransferase expression assay indicated that the region around HS1 did not show any activity, whereas the upstream region up to -457 had promoter activity in hepatoma cells. Most of this activity was lost by a 5'-deletion from -286 to -225. Further analysis identified a cluster of three cis-acting regions from -279 to -216, which are named boxes A, B and C. These regions did not have any independent effect, but the inclusion of all regions were synergistic. These regions were not active in hepatocytes, suggesting that they have cell-type specificity. A gel mobility shift assay indicated that unidentified, but distinct, nuclear proteins bound to the three boxes. These results suggest that transcriptional regulation of the M gene involves alteration of chromatin structure and binding of proteins to three cis-acting elements.

Animals↗

Immunohistochemical demonstration of tissue kallikrein in the neurons of rat brain.

The distribution of tissue kallikrein (EC.3.4.21.35) in the rat brain was investigated by an enzyme-linked immunosorbent assay (ELISA) and immunohistochemical technique using antiserum against rat urinary kallikrein. More than 75% of the total amount of kallikrein in the extracts of the cerebral cortex and brain stem was determined by the ELISA to be in the form of prokallikrein, suggesting that the greater part of the enzyme exists in the form of pro-enzyme in the central nervous system. Furthermore, immunohistochemical examination revealed that, although the kallikrein-positive cells were widespread and scattered in the brain, the immunoreactive substances preferentially locate in the neuronal cell bodies and their processes in both the cerebral cortex and brainstem.

Animals↗

The ter primordial germ cell deficiency mutation maps near Grl-1 on mouse chromosome 18.

A single recessive gene, ter (teratoma), causes germ cell deficiency and a high incidence of congenital testicular teratomas in the 129/Sv-ter strain of the mouse. Linkage analyses between the ter gene and 36 marker genes of 19 chromosomes were performed with matings between the C57BL/6J-ter congenic strain and four inbred strains. Results showed that the ter gene was linked to D18Mit9, D18Mit14, and D18Mit17 on Chromosome (Chr) 18. Gene order estimated on the basis of recombination distance (in centimorgans) was [centromere-D18Mit14-5.1 (cM)-ter-0 (cM)-D18Mit17-23.8 (cM)-D18Mit9]. D18Mit17 is the microsatellite DNA of the Grl-1 (glucocorticoid receptor-1) locus. We conclude that the ter gene is closely linked to Grl-1 on Chr 18 and is a new mutation involving the developmental modification of primordial germ cells in mice.

Animals↗

Experimental study and clinical use of poly(vinyl acetate) emulsion as liquid embolisation material.

A new material, an emulsion of poly(vinyl acetate) was experimentally developed and clinically used to overcome several disadvantages in currently used liquid embolisation materials. The emulsion microparticles, 0.3-0.7 microns in size, possessed cationic charge on the surface and hence aggregated immediately on contact with fluids containing anions. This inert polymer has the advantage that it does not induce a deleterious reaction in living tissue. Moreover, its medium is water and it is not adhesive, like the cyanoacrylates. Several concentrations of emulsion were injected into the renal arteries of dogs. For the investigation of tissue reactions and the possibility of recanalisation, the emulsion was injected into rats both subcutaneously and into the renal arteries. The renal artery injections in dogs showed adequate radiopacity and consistent complete occlusion. The lower the concentration of the emulsion, the smaller the arteries which could be occluded. Even at very low concentrations, however, venous occlusion did not occur. Histological study of the embolised rat kidney revealed no detectable damage in the vessel wall and no recanalisation for up to 6 months. The subcutaneously injected PVAc emulsion elicited mononuclear cell infiltration and gradual centripetal fibrosis, without any deleterious effect on the surrounding tissue. A cerebral arteriovenous malformation (AVM) was embolised using the material. Histology of the resected nidus showed findings similar to those in the animal experiments.

Adult↗

Surgical treatment of hepatocellular carcinoma.

The effect of surgical treatment for hepatocellular carcinoma (HCC) was evaluated in 149 resected cases, 83.2% of which were associated with liver cirrhosis. The 3- and 5-year survival rates were 60.1% and 39.4%, respectively. The mortality rate was 4.1%. In patients aged over 70 years, liver cirrhosis was found in 53.3% of cases and the mortality rate was 6.7%. The 3- and 5-year survival rates were 50.8% and 33.9%, respectively. Factors that significantly affected survival for more than 5 years were a tumor size of less than 3 cm, Stage I disease, vp(-), IMo, and diploid type. The 5-year survival rate for patients with a single tumor of 3 cm or less was 54.2%, regardless of the surgical procedure. All 15 patients with a solitary tumor of 2 cm or less (Stage I, small liver tumor) were alive with a 5-year survival rate of 100%. The problem is the treatment of patients with a tumor measuring 3-5 cm in diameter and associated liver cirrhosis, because their prognosis after surgery is the worst. HrS (subsegmentectomy) is the minimal procedure of limited hepatectomy for these cases with postoperative multidisciplinary therapy.

Adult↗

Reproductive failure in mice chronically infected with Toxoplasma gondii.

Nya: NYLAR female mice infected with Toxoplasma gondii for 1 and 2 months were cohabited with normal males for 1 week, then sequestered individually to monitor their reproductive performance. Mice bred 1 month postinfection (p.i.) exhibited reproductive failure, with 1 of 16 females delivering 2 sickly pups; in others, interruption of pregnancy and fetal wastage occurred. Mice infected for 2 months were uniformly infertile. Vaginal lavage showed cessation of estrus cycling and constant diestrus cytology at as early as 1 month p.i. Histologic examination of the ovaries revealed impaired folliculogenesis and few corpora lutea, if any. Uterine atrophy was marked. Coronal sections of the cerebrum disclosed widespread vasculitis, focal disruptions of the ependymal cell layer lining the lateral and third ventricles, and periventricular edema. We suggest that the reproductive failure of the infected mice is due to an acquired hypogonadotropic hypogonadism secondary to hypothalamic dysfunction.

Adrenal Glands↗

Occurrence of carbamoyl-N-hydroxy derivatives of saxitoxin and neosaxitoxin in a xanthid crab Zosimus aeneus.

Two novel paralytic toxins were isolated from toxic specimens of a xanthid crab Zosimus aeneus inhabiting Ishigaki Island, Okinawa. The structures of two of these were deduced to be carbamoyl-N-hydroxysaxitoxin and carbamoyl-N-hydroxyneosaxitoxin based on electrophoresis, high performance liquid chromatography, electrospray ionization mass spectrometry, 1H NMR, 13C NMR and conversion experiments. They showed specific toxicities of 1700 and 1400 mouse units per mg on i.p. injection into mice.

Animals↗

Poisoning by the red alga 'ogonori' (Gracilaria verrucosa) on the Nojima Coast, Yokohama, Kanagawa Prefecture, Japan.

A food poisoning case due to the ingestion of 'ogonori', an edible red alga, occurred at Yokohama, Kanagawa Prefecture, Japan, in late October 1993, resulting in two victims, including one death (female). No causative agent present in the ogonori was found from a routine bioassay for marine toxins. From the production of increased amounts of prostaglandins (PGs), mainly PGE2, by the alga on stimulation by cutting or soaking in fresh water, and further increase of PGE2 by addition of arachidonic acid, it appeared that an enzyme, probably fatty acid cyclooxygenase, in the ogonori and the body of the victim, was acting on the highly unsaturated fatty acids in the oil of the ingested seafood and in the blood hemorrhaged from the stomach of the victim. This resulted in the production of over 30 mg of PGE2 and small amounts of other PGs in a comparatively short time. With this dosage the victim suffered from nausea, vomiting, and hypotension, and died of hypotensive shock. PGE2 seems to work more selectively on females. This type of poisoning is very unusual, and differs from the more familiar forms of poisoning occurring after ingestion of marine organisms.

Animals↗

Biotransformation of (+)-camphor by cultured cells of Eucalyptus perriniana.

Seven new biotransformation products were isolated from a jar fermentor culture of Eucalyptus perriniana following administration of (+)-camphor. The main product was (1S,4R,6S)-6-hydroxybornan-2-one 6-O-beta-D-glucopyranoside. The minor components were (1S,4R,6R)-6-hydroxybornan-2-one 6-O-beta-D-glucopyranoside, (1R,4S,6S)-6-hydroxybornan-2-one 6-O-beta-D-glucopyranoside, (1R,4R,5R)-5-hydroxybornan-2-one 5-O-beta-D-glucopyranoside, (1R,3R,4S)-3-hydroxybornan-2-one 3-O-beta-D-glucopyranoside, (1R,4R,7R)-8-hydroxybornan-2-one 8-O-beta-D-glucopyranoside and 2-(4-oxo-2,2,3-trimethylcyclopentyl)-ethyl-beta-D-glucopyranoside. All products were mono-glucosides and the oxygen function was introduced before glucosylation. Reduction of the ketone group of camphor was not observed.

Biotransformation↗

A survey of spinal cord injuries resulting from sport.

We surveyed 35 patients who had been admitted to the Hakone National Hospital with a traumatic spinal cord injury (SCI) resulting from sports accidents, from 1975 to 1991. There were 32 males and three females. Thirty-one patients (88.6%) under the age of 30 had been injured. The most common sport was swimming (51.4%), followed by gymnastics (22.8%). The most common factors were conceit and lack of skill. The injuries were predominantly at the C4-5-6 level. Thirty-four of the patients had a cervical spine injury. Paralysis at the sixth cervical level occurred in 15 cases. Regarding the mechanism of injury, impact on the ground due to misjudgment in the depth of water was the most frequent in swimming; and failure in a somersault the most frequent in gymnastics. The most important point raised in the prevention of SCI sport was education about the dangers during elementary schooling.

Adolescent↗

Problems of long-term hospitalised cervical spinal cord injury patients in university hospitals.

Of the 215 cervical spinal cord injury (CSCI) patients treated in Tokai University Hospital over the last 17 years, 42 who were hospitalised for more than 90 days were selected as the subjects for this survey. They were divided into two groups: group A: patients hospitalised for 180 days or more; and group B: patients hospitalised for more than 90 but less than 180 days. The aspects surveyed were: the number of days of hospitalisation, type of injury, level of spinal cord injury, extent of spinal cord paralysis, assessment based on Frankel's classifications, whether a tracheotomy was performed or not, surgical treatment, complications, and the clinical course after discharge. The most common injury for the 13 patients in group A (average stay 281 days) was a fracture-dislocation, followed next by those with a burst fracture. The majority of the 28 patients in group B (average stay was 117 days) had a central type of spinal cord injury. Characteristics observed in group A in particular were: higher segment injuries to the cervical spinal cord, complete paralysis, respiratory complications such as pneumonia, tracheotomy, or a waiting time of at least 6 months before discharge, in cases where a transfer to a rehabilitation hospital was possible. The major problems of treating CSCI patients in university hospitals are that severe cases, which are concentrated in university hospitals, are forced to occupy private rooms for long term treatment, and there is a difficulty in transferring these patients to rehabilitation hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗