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Biomedical subjects

M Hoshi

Publications and source records attributed to M Hoshi.

At least 73 records · Page 4Linked to original sources

Thyroid abnormality trend over time in northeastern regions of Kazakstan, adjacent to the Semipalatinsk nuclear test site: a case review of pathological findings for 7271 patients.

From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population.

Adenocarcinoma, Follicular↗

High incidence of micronuclei in lymphocytes from residents of the area near the Semipalatinsk nuclear explosion test site.

The Semipalatinsk area is highly contaminated with radioactive fallout from 40 years of continuous nuclear testing. The biological effects on human health in this area have not been studied. Significant remaining radioactivities include long-lived radioisotopes of 238,239,400Pu, 137Cs and 90Sr. To evaluate the long-term biological effects of the radioactive fallout, the incidence of micronuclei in lymphocytes from residents of the area was observed. Blood was obtained from 10 residents (5 females and 5 males, aged 47 to 55 years old) from each of the 3 areas of Znamenka, Dolon and Semipalatinsk, which are about 50-150 km from the nuclear explosion test site. For micronucleus assay, PHA-stimulated lymphocytes were cultured for 72 h and cytochalasin B was added at 44 h for detecting binuclear lymphocytes. Five thousand binuclear lymphocytes in each resident were scored. The means of micronucleus counts in 1,000 lymphocytes in residents of Semipalatinsk, Dolon and Znamenka were 16.3, 12.6, and 7.80, respectively, which were higher than those of the normal Japanese persons (4.66). These values were equivalent to the results obtained from 0.187-0.47 Gy of chronic exposure to gamma-rays at a dose rate of 0.02 cGy/min. The high incidence of micronuclei in residents of the Semipalatinsk nuclear test site area was mainly caused by internal exposure rather than external exposure received for the past 40 years.

Bone Marrow↗

Hypoglossal neurinoma--two case reports.

Two patients presented with hypoglossal neurinoma extending both intra- and extracranially. A 63-year-old male presented with right trigeminal neuralgia and hypoglossal nerve paresis. The intracranial part of the tumor was removed totally via a suboccipital craniectomy. Over-coagulation of the venous collaterals, particularly the emissary veins, resulted in dural venous sinus thrombosis and cerebellar infarction. Unfortunately this patient died. A 48-year-old male presented with pareses of the VII, IX, X, XI, and XII cranial nerves and cerebellar sign. The tumor extended both extra- and intracranially, and was completely removed by opening the hypoglossal canal and the jugular foramen without over-coagulation of the venous collaterals. Preservation of the venous collaterals is very important for the prevention of postoperative venous complications.

Cerebral Angiography↗

Activation of the proteasomes of sand dollar eggs at fertilization depends on the intracellular pH rise.

The mechanism of the activation of intracellular proteasomes at fertilization was measured in living sand dollar eggs using the membrane-impermeant fluorogenic substrate, succinyl-Phe-Leu-Arg-coumarylamido-4-methanesulfonic acid. When the substrate was microinjected into unfertilized eggs, the initial velocity of hydrolysis of the substrate (V0) was low. V0 measured 5 to 10 min after fertilization was five to nine times the prefertilization level and remained high throughout the first cell cycle. Hydrolysis of the substrate was inhibited by clasto-lactacystin beta-lactone, a specific inhibitor of the proteasome. There has been in vitro evidence that calcium may be involved in regulation of proteasome activity to either inhibit the increase in peptidase activity associated with PA 28 binding to the 20S proteasome or stimulate activity of the PA 700-proteasome complex. Since both intracellular free Ca2+ concentration ([Ca2+]i) and intracellular pH (pHi) increase after fertilization, hydrolysis of the proteasome substrate was measured under conditions in which [Ca2+]i and pHi were varied independently during activation. When the pHi of unfertilized eggs was elevated by exposure to 15 mM ammonium chloride in pH 9 seawater, V0 increased to a level comparable to that measured after fertilization. In contrast, [Ca2+]i elevation without pHi change, induced by calcium ionophore in sodium-free seawater, had no effect on V0 in the unfertilized egg. Moreover, when unfertilized eggs were microinjected with buffers modulating pHi, V0 increased in a pH-dependent manner. These results indicate that the pHi rise at fertilization is the necessary prerequisite for activation of the proteasome, an essential component in the regulation of the cell cycle.

Ammonium Chloride↗

G-protein betagamma subunit-dependent phosphorylation of 62-kDa protein in the early signaling pathway of starfish oocyte maturation induced by 1-methyladenine.

In starfish oocytes, maturation is induced by a hormone, 1-methyladenine (1-MA), that binds to the receptors exposed to the outer surface of the plasma membrane. The signal of 1-MA stimulates the heterotrimeric G protein, resulting in dissociation of the betagamma subunit of G protein (Gbetagamma) from a pertussis toxin-sensitive Gi-type alpha subunit. To investigate the targets for Gbetagamma, we analyzed 1-MA- or Gbetagamma-dependent phosphorylation using in vivo and in vitro systems. A 62-kDa protein was phosphorylated immediately after 1-MA treatment in intact oocytes. In the cell-free preparations, the 62-kDa protein was also phosphorylated on serine residue(s) immediately after addition of 1-MA or Gbetagamma. The Gbetagamma-dependent phosphorylation of the 62-kDa protein was inhibited by wortmannin or LY294002, which are mechanistically different inhibitors of phosphatidylinositol 3-kinase (PI3K). LY294002 also inhibited Gbetagamma- as well as 1-MA-induced maturation of oocytes. Taken together, these results indicate that the 62-kDa protein functions downstream of Gbetagamma and PI3K in the early signaling pathway of 1-MA-induced starfish oocyte maturation. The phosphorylation of the 62-kDa protein may be required for the activation of maturation-promoting factor.

Adenine↗

Induction of germinal vesicle breakdown in a cell-free preparation from starfish oocytes.

Incubation of isolated germinal vesicles in the homogenate from maturing starfish oocytes resulted in synchronous germinal vesicle breakdown (GVBD), and chromosome condensation and gathering within 30 min. GVBD in this cell-free system required aerobic conditions. The endogenous ATP-generation system was preserved in the homogenate and effective under aerobic conditions, and thus exogenous ATP was not added to the homogenate. Injection of the homogenate into immature starfish oocytes induced meiotic maturation without 1-methyladenine, indicating high activity of maturation-promoting factor (MPF) in the homogenate. MPF activity in the homogenate was stable for 2 h at room temperature, while it disappeared within 1 h in the supernatant prepared by centrifugation of the homogenate. This disappearance of MPF activity is regulated by cyclin B destruction, similar to that seen in vivo.

Animals↗

Sequence analysis of cDNAs encoding precursors of starfish asterosaps.

To understand how starfish sperm activating peptides (asterosaps) are synthesized in the ovary, we cloned cDNAs encoding asterosaps and elucidated their nucleotide sequences. The mRNA encoding asterosaps was synthesized only in the oocytes, but not in the follicle cells, and the length was 3.7 kb. The cDNA clones contained multiple isoforms of asterosaps. We assume that asterosap precursors are large prepolypeptide chains with an unusual "rosary-type" structure made of 10 successive similar stretches of 51-55 residues. Each stretch finishes with a "spacer" of 17-21 residues immediately followed by the sequence of one asterosap isoform. The N-terminal of this precursor has 19-21 successive glutamine-rich repeating units. Maturation of the precursor may require endopeptidases that cleave both C- and N-sites of lysine-arginine.

Acrosome Reaction↗

Neutral and acidic glycosphingolipids in glucocorticoid-induced cataract in chick lens.

Administration of glucocorticoids induces transient cataract in 15-day-old chick embryos within 48 hr, and the opaque lens again becomes clear within the subsequent 48 hr. Oxidative stress is likely to be involved in the process of cataract formation, resulting in the appearance of numerous vacuoles around the perinuclear region. Chick lens contained low amounts of glycosphingolipids, which mainly consists of GM3, GD3, sialyl-LewisX gangliosides and glucosylceramide. Most lens gangliosides were immunohistochemically detected in lens epithelia, annular pads and developing fibers, but not in perinuclear and nuclear regions. Since cell surface gangliosides, for example GM3 and sialyl-LewisX gangliosides, are involved in cell adhesion, weak cell-to-cell interactions in the perinuclear and nuclear regions may allow vacuole formation in steroid-induced cataractogenesis.

Animals↗

Cloning and characterization of the human UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene.

A novel human gene determining a polypeptide product of 478 residues with an estimated molecular mass of 55 kDa, which has significant homology and structural similarity to Bos UDP-N-acetylglucosamine: alpha-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase (GnT-IV), was cloned from the commonly deleted region in pancreatic cancer at 12q21. The gene is composed of at least six exons, and the last three exons cover the open reading frame. Different sized transcripts, 3.8-kb in the heart, brain, and fetal brain and 2.8-kb and 1.7-kb in the testis were observed by Northern blot analysis. By reverse transcription-polymerase chain reaction, expression was also observed in the adult brain, liver, and adrenal gland, but not in pancreas. Because of its significant homology and structural similarity to Bos GnT-IV, it is potentially the gene encoding human GnT-IV or its homologue, which had been one of two genes remaining to be cloned in the human GnT family.

Adult↗

Functional interactions between sulphated polysaccharides and proacrosin: implications in sperm binding and digestion of zona pellucida.

Acrosin is a serine protease located within mammalian acrosome as inactive proacrosin. Sulphated polymers bind to proacrosin and acrosin, to a domain different from the active site. Upon binding, these polymers induce proacrosin activation and some of them, such as fucoidan, inhibit sperm binding to the zona pellucida. In this work we have studied the interaction of solubilised zona pellucida glycoproteins (ZPGs), heparin and ARIS (Acrosome Reaction Inducing Substance of Starfish) with boar and human acrosin. We have found that ARIS, solubilised ZPGs and fucoidan, but not heparin, inhibit the binding of the monoclonal antibody against human acrosin C5F10 to boar or human proacrosin. These results suggest that fucoidan, solubilised ZPGs and ARIS bind to a related domain on the proacrosin surface. Moreover, ARIS was able to induce human proacrosin activation. On the other hand, neither ARIS nor heparin from porcine intestinal mucosa or bovine lung induced hamster sperm acrosome reaction or sperm motility. Recent data showed that acrosin is involved in dispersal of the acrosomal matrix after acrosome reaction. Thus, the control of the ZPG glycan chains over proacrosin activation may regulate both sperm penetration rate and limited proteolysis of zona pellucida proteins.

Acrosin↗

Sulfated O-linked glycans of the vitelline coat as ligands in gamete interaction in the ascidian, Halocynthia roretzi.

In the ascidian Halocynthia roretzi, sperm-egg binding is probably mediated through the interaction between alpha-L-fucosidase present on the sperm surface and anionic saccharide chains of the egg vitelline coat. To characterize biologically active glycans, total glycans were chemically released from the glycopeptide fraction of the vitelline coat. The fraction of uncharged glycans and two fractions of negatively charged glycans were separated by diethylaminoethyl-anion exchange chromatography. In a competitive inhibition assay of fertilization, both anionic fractions showed inhibitory activity, with more anionic glycans being most potent, while uncharged glycans were biologically inactive. Chemical desulfation combined with a competitive inhibition assay of fertilization and ion analysis determined that sulfate groups were responsible for anionic character and crucial for biological activity. Monosaccharide analysis of anionic fractions showed a high content of N-acetylgalactosamine, galactose, xylose and the presence of arabinose, mannose, N-acetylglucosamine, glucose and rhamnose. Glycans were O-linked and galactose and xylose residues were detected at reducing termini. Linkage analysis suggested that 1,4-linked xylose, 1,3-linked galactose and N-acetylgalactosamine residues, substituted to different degrees by sulfate groups on the C-3 and C-4 carbons, respectively, constituted the core structures of anionic glycans.

Animals↗

Reduction of the gamma-ray component from 252Cf fission neutron source--optimization for biological irradiations and comparison with MCNP code.

Gamma-rays contribute 33% of the absorbed dose from an unfiltered 252Cf fission neutron source. To reduce this gamma-ray component and to enable radiobiological experiments at as high a dose rate as possible, Monte Carlo calculations for several filter materials (Al, Fe, Pb and concrete) have been made using MCNP neutron and photon transport code version 4a. A lead filter of thickness 4 cm was found to reduce the gamma-ray component to 6.7% of the total dose whilst reducing the neutron dose by only about 10%. Such a filter was installed at the MRC 252Cf neutron irradiation facility and dosimetric measurements were made using a TE-TE chamber and a 7LiF(Mg, Cu, P) TLD. Monte Carlo simulations agree with experimental measurements of neutron and gamma-ray doses within 6%. V79-4 Chinese hamster cells were irradiated with lead-filtered and unfiltered neutrons and also with 60Co gamma-rays at two dose rates. The survival fraction obtained for each radiation was consistent with the reduced gamma-ray dose. The relative biological effectiveness for neutrons alone, corrected for gamma-ray effects, was found to be 9.2 +/- 3.4 from the initial slopes and 3.1 +/- 0.5 at 10% survival, both relative to the acute gamma-rays.

Animals↗

Expression of the DMBT1 gene is frequently suppressed in human lung cancer.

DMBT1 (deleted in malignant brain tumors) is a candidate tumor suppressor gene that has been mapped to chromosome 10q25.3-q26.1, a region in which frequent loss of heterozygosity (LOH) has been observed in several human tumors. Since DMBT1 is highly expressed in the lung, we analyzed LOH at the DMBT1 locus and expression of this gene in lung cancer. Thirty-five (53%) of 66 primary lung cancers showed LOH, and diminished expression of DMBT1 was observed in 20 (91%) of 22 lung cancer cell lines: three (14%) of them showed loss of expression. We further determined the primary structure of DMBT1 and analyzed genetic alterations in this gene using 23 lung cancer cell lines. Two (9%) of them had homozygous deletion within the gene, and two cell lines had genetic aberrations: one was a rearrangement involving exons 5 and 6, and the other was a missense mutation at codon 52. These results suggest that inactivation of the DMBT1 gene plays an important role in human lung carcinogenesis.

Agglutinins↗