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Biomedical subjects

T Shintani

Publications and source records attributed to T Shintani.

At least 37 records · Page 2Linked to original sources

Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family.

PTPzeta/RPTPbeta is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. Although several ligands of PTPzeta have been identified, proteins interacting with the intracellular region of PTPzeta are still unknown. We performed yeast two-hybrid screening using the intracellular region of PTPzeta as a bait, and found that the C-terminal sequence of PTPzeta binds to the PSD-95/SAP90 family through the second PDZ domain. Immunohistochemical analysis revealed that PTPzeta and PSD-95/SAP90 are similarly distributed in the dendrites of pyramidal neurons of the hippocampus and neocortex. Furthermore, subcellular fractionation experiments indicated that PTPzeta is concentrated in the postsynaptic density fraction. These results suggested that PTPzeta is involved in the regulation of synaptic function as postsynaptic macromolecular complexes with PSD-95/SAP90.

Animals↗

Interphase fluorescence in situ hybridization overcomes pitfalls of G-banding analysis with special reference to underestimation of chromosomal aberration rates.

Fluorescence in situ hybridization (FISH) is suitable for detecting different types of chromosome aberrations on interphase nuclei even in specimens with no or few chromosome metaphases. However, it is not known why FISH is superior to conventional G-banding analysis. The sensitivity of interphase FISH was compared to that of G-banding analysis in 288 leukemia/lymphoma patients for 10 different types of chromosome aberrations: t(9;22) (M- and m-BCR), t(8;21), 11q23 abnormalities, t(15;17), del(5)/-5, del(13)/-13, +8, -7, and +12. The results revealed that t(15;17) positive cells could not proliferate well in culture, leading to underestimation of abnormality by G-banding. Monosomy 7 in acute myelocytic leukemia (AML) and myelodysplastic syndrome (MDS) as well as trisomy 12 and deletion chromosome 13 in chronic lymphocytic leukemias (CLL) were also severely underestimated by G-banding. On the other hand, no discrepancies were observed in t(8;21), t(9;22), translations involving 11q23, or in trisomy 8. These findings indicate the superiority of interphase FISH over conventional cytogenetics for detecting chromosome abnormalities in small clones, especially for monosomy 7 or (15;17) translocations.

Chromosome Aberrations↗

Effect of Uncariae ramulus et Uncus on endothelium in spontaneously hypertensive rats.

The protective effect of the extract of Uncariae ramulus et Uncus (URE) against endothelium disorder due to hypertension was investigated. We administered low (150 mg/kg/day) and high (450 mg/kg/day) doses of URE orally to spontaneously hypertensive rats for 8 weeks. Endothelium dependent vasodilatation by acetylcholine increased significantly in the high URE group compared with the control group. Endothelium dependent vasocontraction by xanthine oxidase decreased significantly in the high URE group compared with the control group. Serum NO2-/NO3- were tended to increase in the high URE group. It is suggested that URE may have a protective effect for the endothelium against the influence of hypertension.

Acetylcholine↗

Chromosomal instability in acute myelocytic leukemia and myelodysplastic syndrome patients among atomic bomb survivors.

To clarify the mechanism of leukemogenesis in atomic bomb survivors, leukemic cells were investigated using fluorescence in situ hybridization (FISH) analysis on the basis of conventional G-banding in patients with a history of radiation exposure and also in de novo patients. Conventional G-banding showed higher incidences (p < 0.005) of structural and numerical abnormalities without any specific types of chromosome aberrations in the group exposed to a dose of more than one Gy, compared to the non-exposed group. FISH analysis revealed significantly higher incidences (P < 0.05) of subclones with monosomy 7 and deletion of the 20q13.2 region, which were not found in conventional cytogenetic analysis in the exposed group (more than one Gy) compared to the non-exposed controls. Furthermore, segmental jumping translocation (SJT) of the c-MYC gene region was observed only in the exposed group. These chromosomal instability suggested that the leukemic cells from the heavily exposed patients contained persistent cellular genetic instability which may strongly influence the development of leukemia in people exposed to radiation.

Adult↗

Radiological states around the Kraton-4 underground nuclear explosion site in Sakha.

A radiological survey around the site of Kraton-4, an underground nuclear explosion (Yield of 20 kt, depth of 560 m, 1978) in Sakha was carried out in March 1998. Gamma survey and in-situ spectroscopy on the ground exhibited quite normal levels: a dose rate of 0.022 microSv/h and Cs-137 surface contamination of less than 1.1 kBq/m2 around the hypocenter. The results suggested no remarkable leakage of radioactivity from the epicenter to the ground surface at least not for non-rare gas elements as of 1998.

Dose-Response Relationship, Radiation↗

High incidence of meningioma among Hiroshima atomic bomb survivors.

Since the atomic bomb explosions in Hiroshima and Nagasaki, high incidences of leukemia, thyroid cancer and other tumors have been reported as atomic bomb-induced tumors. We investigated the incidence of meningioma among Hiroshima atomic bomb survivors. Sixty-eight patients surgically treated for meningioma who had been within 2.0 km of the hypocenter of the explosion were identified. Six hundred and seven non-exposed patients with meningioma were also studied. Treatment dates were from 1975 to 1992. The incidences of meningioma among 68 subjects within 2.0 km and 607 non-exposed patients were 8.7 and 3.0 cases per 10(5) persons per year, respectively. The incidences of meningioma among the survivors of Hiroshima in 5-year intervals since 1975 were 5.3, 7.4, 10.1, and 14.9, respectively. The incidences of meningioma classified by distances from the hypocenter of 1.5-2.0 km, 1.0-1.5 km and less than 1.0 km were 6.3, 7.6 and 20.0, respectively. The incidences of meningioma classified by doses to the brain of 0-0.099 Sv, 0.1-0.99 Sv and more than 1.0 Sv were 7.7, 9.2 and 18.2, respectively. The incidence of meningioma among Hiroshima atomic bomb survivors has increased since 1975. There was a significant correlation between the incidence and the dose of radiation to the brain. The present findings strongly suggest that meningioma is one of the tumors induced by atomic bombing in Hiroshima.

Brain↗

Waianae Diet Program: long-term follow-up.

A long-term follow-up was conducted on 82 participants from prior programs based on ad libitum feeding of a traditional Hawaiian diet. Follow-up period ranged from 12 months to 90 months and averaged 33.67 months. An average weight loss of 15.1 pounds was maintained over 7.5 years of follow-up (p < 0.0005) even when stratified over two year intervals, suggesting that this type of program may be an effective long-term weight loss intervention.

Adult↗

A light and electron microscopic analysis of the convergent retinal and visual cortical projections to the nucleus of the optic tract (NOT) in the pigmented rat.

It is generally known that the nucleus of the optic tract (NOT) subserves visuomotor relations between the retina and preoculomotor structures as the only subcortical pathway mediating optokinetic responses (OKR) in mammals. We have examined the projections from the retina and visual cortical areas (areas 17, 18a and 18b) to NOT using tracers (wheat germ agglutinin-conjugated horseradish peroxidase, WGA-HRP and cholera toxin B subunit, CTB) in order to clarify how these two different functional inputs to OKR are organized. CTB injection into the vitreous body resulted in anterograde label almost exclusively in the contralateral NOT. Ultrastructually, the size of the retinal axon terminals was small (up to 0.7 micron in diameter), contained round synaptic vesicles and pale mitochondria, and made asymmetrical synaptic contacts with both GABA-positive and GABA-negative NOT neurons. Visual cortical area 17 and the transitional area between area 17 and 18a, or between area 17 and 18b projected their axons to the ipsilateral NOT. Ultrastructually, the size of the cortical axon terminals was small (up to 0.5 micron in diameter), contained round synaptic vesicles, and made asymmetrical synaptic contacts only with GABAnegative NOT neurons. With light and electron microscopical observation, there was a considerable overlap in the cortico-NOT and retino-NOT projection pattern: GABA-negative (presumably NOT projection) neurons simultaneously receive input from both cortical and retinal terminals. From these results, it seems reasonable to postulate that inputs from visual cortical areas in the pigmented rat cooperate with those from the retina in controlling OKR.

Animals↗

Cloning and expression of a unique inorganic pyrophosphatase from Bacillus subtilis: evidence for a new family of enzymes.

An open reading frame located in the COTF-TETB intergenic region of Bacillus subtilis was cloned and expressed in Escherichia coli and shown to encode inorganic pyrophosphatase (PPase). The isolated enzyme is Mn2+-activated, like the authentic PPase isolated from B. subtilis. Although 13 functionally important active site residues are conserved in all 31 soluble PPase sequences so far identified, only two of them are conserved in B. subtilis PPase. This suggests that B. subtilis PPase represents a new family of soluble PPases (a Bs family), putative members of which were found in Archaeoglobus fulgidus, Methanococcus jannaschii, Streptococcus mutans and Streptococcus gordonii.

Amino Acid Sequence↗

The effect of adenotonsillectomy in children with OSA.

Adenotonsillar hypertrophy and abnormal facial morphology are thought to be important for the occurrence of obstructive sleep apnea syndrome (OSA). We evaluated the effects of adenidectomy and/or tonsillectomy and the relationship between the treatment results and facial morphology in 134 children with OSA. Significant improvements in apnea-hypopnea indes (AHI) and lowest blood oxygen saturation (SaO2) were noted and 78.5% of the patients improved after adenoidectomy and/or tonsillectomy. Additional operations were needed in two out of 13 cases of the adenoidectomy group and two out of four cases of the adeno-monotonsillectomy group. In the adenotonsillectomy group, the unimproved children tended to have smaller tonsils, narrower epipharyngeal airspace, and more poorly-developed maxillary and mandibular protrusion than the improved children.

Adenoidectomy↗

Neurons as well as astrocytes express proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene was replaced with the LacZ gene.

PTPzeta/RPTPbeta is a receptor-like protein tyrosine phosphatase expressed as a chondroitin sulfate proteoglycan. We generated mice in which the PTPzeta gene was replaced by the LacZ gene by gene targeting. Analysis of heterozygous PTPzeta-targeted mice allowed us to identify PTPzeta-producing cells during development by examining expression of the LacZ gene. LacZ expression was detected only in the central nervous system throughout development from embryonic day 8.5. In the postnatal period, subsets of neurons and astrocytes in the brain, including pyramidal cells and astrocytes in the hippocampus, expressed LacZ. Primary cultures of cells from the cerebral cortex of embryonic day 16 mice also indicated that both neurons and astrocytes were positive for LacZ. These results indicated that neurons and astrocytes express PTPzeta.

Animals↗

Isodicentric chromosome 21: a novel aberration in acute myeloid leukemia.

We present here a 78-year-old female patient with acute myeloid leukemia (AML), French-American-British classification M2, exhibiting isodicentric chromosome 21, idic(21)(q22), at the time of diagnosis. The patient had three idic(21)(q22), besides the del(5)(q13q32), add(21)(q22), dic(21;22) (q22;q13), and +22. Fluorescence in situ hybridization studies with whole-chromosome painting and centromere-specific probes for chromosome 21 verified the diagnosis of idic(21)(q22). There were no distinct clinicohematological characteristics of AML with isodicentric 21. The patient was treated with remission-induction therapy followed by consolidation therapy. Two years later, the patient showed the disappearance of isodicentric 21 but retained del(5)(q13q32) and gained other chromosomal abnormalities, +add(17)(p11) and -16. To our knowledge, this is the first report of AML with acquired idic(21)(q22).

Aged↗

Vertical gaze palsy induced by midbrain lesions and its structural imaging.

We experienced four cases of vertical gaze palsy induced by midbrain lesions. Lesions commonly covered the rostral midbrain, including the rostral interstitial nucleus, dorsomedial to the red nucleus. Two of the four cases resulted from vascular insult, in which a single, unpaired perforator is supposed to innervate the rostral midbrain and medial thalamus bilaterally. One case showed vertical gaze palsy accompanied by bilateral ptosis. The findings agree with recent experimental evidence that a neural substrate in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus. The remaining two cases, a brain hemorrhage and an inflammatory tumor, showed unilateral lesions of the rostral midbrain. In these cases, vertical gazes were not abolished, but were limited in an incomplete way. This may be explained by partial damages of the descending fibers, some of which decussate through the posterior commissure before it reaches the oculomotor nucleus. Thus, clinical signs and symptoms were clarified based on anatomical and physiological points of view.

Adult↗

Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma associated with 17p abnormality.

Fluorescence in situ hybridization (FISH) was performed in 17 myeloid leukemia patients and seven lymphoid leukemia/ lymphoma patients who exhibited chromosomal abnormalities on the short arm of chromosome 17, in order to detect a commonly deleted region on chromosome band 17p13. Twenty-four leukemia/lymphoma patients studied cytogenetically at our institution over a period of 10 years had detectable 17p abnormalities such as translocation (six patients), addition (11 patients) and deletion of 17p13 (seven patients). A 17p abnormality was the only abnormality present in three patients. Most of the patients had additional complex cytogenetic abnormalities. The diagnosis was acute myeloid leukemia (AML) in 10 patients, two each with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) and the remaining three with malignant lymphoma (ML). Seven cosmid probes (D17S34, cCI17-624, cCI17-453, D17S379, cCI17-636, cCI17-732 and TP53) which mapped on 17p13 were used to analyze the allelic deletion. Eighty percent (19 out of 24) of the informative leukemia patients exhibited allelic loss in 17p13.3 at cC17-624. The smallest region of an overlapping deletion was observed on chromosome band 17p13.3 between cCI17-624 and cCI17-453. Patients with translocation involving 17p also showed deletion at cCI17-624 and cCI17-453. We hypothesize that this region contains a novel tumor suppressor gene(s) that is involved in leukemogenesis.

Adult↗

[Obstructive sleep apnea in children with cerebral palsy].

To determine the etiology of obstructive sleep apnea (OSA) in children with cerebral palsy (CP), a survey using a questionnaire was conducted on parents of 233 CP children (1-5 years old, mean age: 2.7) and on those of 343 control children during a routine medical check-up at the age of three. The prevalence of habitual snoring and nasal obstruction was 63 and 20% in CP children, which were significantly higher than in control children. Sleep apnea episodes and stridor were noted in 19.7 and 15.4% of CP children. A screening sleep study was performed using Apnomonitor II and a pulseoximeter (Pulsox 5) in 48 CP children whose questionnaires revealed habitual snoring and sleep apnea, and it was found that 27 and 58% of the children had on apnea-hypopnea index (AHI) of greater than 5 and a low level of SaO2 (LSaO2) of less than 85%, respectively. When another 10 CP children visited our hospital for treatment of severe OSA, precise evaluations including pharyngeal pressure and fiberscopic examination during sleep as well as a sleep study using an inductive prezysmograph (Respigraph) were performed. Adenoid and/or tonsillar hypertrophy were noted in only 4 children, and the main cause of sleep apnea in the other 6 children was pharyngeal collapse at the lingual base. Their OSA was successfully treated by adenotonsillectomy in 2 children, adenotomy in 2 children, UPPP and lingualplasty in 1 child, tracheostomy in 2 children, and nasal CPAP in 1 child. Before treatment of OSA in CP children, precise evaluation is recommended in order to perform appropriate treatment.

Adenoidectomy↗

Engineering of porcine pepsin. Alteration of S1 substrate specificity of pepsin to those of fungal aspartic proteinases by site-directed mutagenesis.

The S1 substrate specificity of porcine pepsin has been altered to resemble that of fungal aspartic proteinase with preference for a basic amino acid residue in P1 by site directed mutagenesis. On the basis of primary and tertiary structures of aspartic proteinases, the active site-flap mutants of porcine pepsin were constructed, which involved the replacement of Thr-77 by Asp (T77D), the insertion of Ser between Gly-78 and Ser-79 (G78(S)S79), and the double mutation (T77D/G78(S)S79). The specificities of the mutants were determined using p-nitrophenylalanine-based substrates containing a Phe or Lys residue at the P1 position. The double mutant cleaved the Lys-Phe(4-NO2) bonds, while wild-type enzyme digested other bonds. In addition, the pH dependence of hydrolysis of Lys-containing substrates by the double mutant indicates that the interactions between Asp-77 of the mutant and P1 Lys contribute to the transition state stabilization. The double mutant was also able to activate bovine trypsinogen to trypsin by the selective cleavage of the Lys6-Ile7 bond of trypsinogen. Results of this study suggest that the structure of the active site flap contributes to the S1 substrate specificity for basic amino acid residues in aspartic proteinases.

Amino Acid Sequence↗

Characterization of rat receptor-like protein tyrosine phosphatase gamma isoforms.

We identified four isoforms of receptor-like protein tyrosine phosphatase gamma (RPTPgamma) from rat brain by cDNA cloning. We designated these molecules RPTPgamma-A, -B, -C, and -S. RPTPgamma-A was the longest form and had the same structure as human and mouse RPTPgamma. RPTPgamma-B lacked the intracellular juxtamembrane 29 amino acids of RPTPgamma-A. RPTPgamma-C had a single phosphatase domain. RPTPgamma-S is an extracellular variant of RPTPgamma. mRNAs of the four isoforms were expressed in the brain, kidney, lung, and heart. Transfection of RPTPgamma-A and -S expression plasmids into COS7 cells resulted in the expression of membrane-bound 190-kDa proteins and secreted 120-kDa proteins, respectively. These molecules were similar to PTPzeta/RPTPbeta with regard not only to structure but also to the presence of both secretory and transmembrane forms. However, RPTPgamma isoforms were not expressed as proteoglycans.

Amino Acid Sequence↗