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S Yamamori

Publications and source records attributed to S Yamamori.

At least 19 recordsLinked to original sources
PubMed2001

Detection of HER-2/neu (c-erb B-2) DNA amplification in primary breast carcinoma. Interobserver reproducibility and correlation with immunohistochemical HER-2 overexpression.

BACKGROUND: Fluorescent in situ hybridization (FISH) has been shown to be one of the most reliable methods with which to estimate the status of the HER-2/neu (or c-erb B-2) oncogene at the DNA level. METHODS: To study interobserver reproducibility and to determine more clinically correlated criteria for HER-2/neu alterations, two observers independently estimated HER-2/neu DNA status. The correlation between the consensus HER-2/neu DNA status by FISH and HER-2/neu protein status detected by immunohistochemistry (IHC) using a polyclonal antibody was studied in 216 surgically resected breast carcinomas and 34 noncancerous tissues. RESULTS: According to the HER-2/CEP17 ratio and mean HER-2 copies per nucleus, agreement level of HER-2/neu amplification was shown to be nearly perfect between two observers (kappa statistic (kappa) = 0.94 and kappa = 0.84). Finally, 40 tumors (19%) were judged to have HER-2/neu DNA amplification, with 6 having low-level amplification (> or = 2 but < 3 folds) and 34 having high-level amplification (> or = 3 folds). One hundred seventy-six other tumors, including 3 tumors that only 1 of the observers determined to be low-level amplifiers, and 34 noncancerous tissues had no detected amplification. The DNA amplification status was concordant between invasive and intraductal components in 14 carcinomas. HER-2/neu protein overexpression of moderate (2+) or high (3+) intensity based on IHC was detected in 51 carcinomas (24%), and was 2+ in 20 carcinomas and 3+ in 31 carcinomas. The HER-2/CEP17 ratio of > or = 2 was concordant with IHC findings of 2+/3+ in 91% of carcinomas (195 of 215 carcinomas), with a sensitivity of 70% (35 of 50 carcinomas) and a specificity of 97% (160 of 165 carcinomas). High-level amplification was detected in 29 of 31 IHC 3+ cases (94%), but in only 5 of 20 IHC 2+ cases (25%) and 0 in 165 IHC 0/1+ cases. All 34 cases with high-level amplification showed an IHC score of 3+ (29 cases) or an IHC score of 2+ (5 cases), but only 1 case was found to have an IHC score of 3+ and the remainder were IHC 0/1+ in 6 low-amplification cases. The concordance rate of the high-level amplification with an IHC score of 3+ was 97% (208 of 215 cases), with a sensitivity of 94% (29 of 31 cases) and a specificity of 97% (179 of 184 cases). CONCLUSIONS: The results of the current study indicated that high-level HER-2/neu amplification and an IHC score of 3+ nearly optimally identified breast carcinomas with clinically and biologically significant HER-2/neu activation. Conversely, it was confirmed that careful interpretation of test results is required in the case of low-level amplification and/or an IHC score of 2+.

Breast Neoplasms↗
PubMed2001

A src family tyrosine kinase inhibits neurotransmitter release from neuronal cells.

Tyrosine kinases are expressed in many tissues, particularly in the central nervous system, and regulate various cellular functions. We report here that a src family tyrosine kinase-specific inhibitor, PP2, enhances neurotransmitter release from PC12 cells and primary cultured neurons. PP2 enhances only Ca(2+)-dependent release; it does not affect basal release. These effects result from an enhancement of vesicular exocytosis and not from the reuptake or refilling of neurotransmitters because Ca(2+)-dependent secretion of an exogenously expressed reporter protein, the human growth hormone (hGH), is also enhanced by PP2. Overexpression of constitutive active v-src, but not of a kinase-inactive mutant, suppressed Ca(2+)-dependent release. In PP2-treated cells, Pyk2, paxillin, and some other proteins showed a decrease in tyrosine phosphorylation, and the enhancement of tyrosine phosphorylation of these proteins in response to Ca(2+) influx was also reduced. Electron and fluorescence microscopy showed that PP2 treatment induced morphological change and decreased phalloidin reactivity at the filopodium-like structures on the processes of PC12 cells. Interestingly, inhibition of actin polymerization with cytochalasin D and latrunculin A enhanced Ca(2+)-dependent, but not basal, release. It is possible that a src family tyrosine kinase, through the regulation of actin dynamics, has an inhibitory function to regulate neurotransmitter release.

Actins↗
PubMed2001

Isochromosome consisting of terminal short arm and proximal long arm X in a girl with short stature.

A 16-year-old girl with short stature, short neck, shield chest, and cubitus valgus was studied. FISH analyses of her structurally altered X chromosome showed a der(X)- (wcpX+,TelXp/Yp++,SHOX++,STS++,KAL-, 37A12-,DXZ1+,XIST++,97L7++,300O13-,404F- 18-,417G15-,404F18-,140A-,TelXq/Yq-). These results, together with the high-resolution banding analysis, indicated her karyotype to be 46,X,der(X)(Xpter-->Xp22.3::Xq22.3--> cen-->Xq22.3::Xp22.3-->Xpter). The der(X) was an isochromosome, consisting of duplicated terminal short arms and duplicated proximal long arms. This in turn suggested that the chromosome was formed through pericentric inversion of an X chromosome, followed by isochromosome formation through sister chromatid exchange at Xp, close to the centromere. Replication R-banding analysis showed that the abnormal X chromosome was late replicating. Analysis of digestion patterns with a methylation-sensitive restriction endonuclease of the phosphoglycerate kinase 1 gene, located in Xq13.3, indicated that its inactivation patterns were completely skewed.

Adolescent↗
PubMed2001

Creatine kinase gene mutation in a patient with muscle creatine kinase deficiency.

BACKGROUND: We describe a 56-year-old woman admitted to the hospital with a diagnosis of acute myocardial infarction without an increase of serum creatine kinase (CK) activity during her clinical course. She died on the 11th hospital day, and the diagnosis was confirmed by autopsy. The patient had had no previous muscular symptoms. METHODS: Expression of the CK-muscle (CK-M) protein in cardiac tissue was examined by immunoblotting and immunochemical staining. CK-M mRNA expression was estimated by semiquantitative reverse transcription-PCR. Gene structure of CK-M was determined by Southern blotting and direct sequencing of 2251 bp. Existence of a point mutation in the CK-M gene was examined by restriction fragment length polymorphism analysis of PCR products (PCR-RFLP) in the patient and in 108 controls. RESULTS: CK-M protein in the myocardial tissue of the patient was substantially lower (103 +/- 7 ng/mg protein) than in control myocardial tissue (35 800 +/- 2860 ng/mg protein). Immunoreactive CK-M in the patient tissue sample was 0.3% of the value for the control sample. CK-M mRNA was 53-fold less in the patient sample compared with the control. This very low expression of CK-M mRNA was considered to be the primary reason for CK-M deficiency. Direct sequencing revealed a point mutation at residue 54 in exon 2, which was specific for the patient. No other abnormalities were found in the CK-M gene of the patient. CONCLUSIONS: This report identifies a molecular abnormality in human CK deficiency and discusses the physiologic relevance of CK-M.

Blotting, Southern↗
PubMed2000

Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism.

The transcriptional start site of the human cholecystokinin (CCK)-A receptor gene was determined by the Capsite Hunting method. Two sequence changes were detected, a G to T change in nucleotide -128, and an A to G change in nucleotide -81. The homozygote (T/T, G/G) was detected in 25 of 1296 individuals (1.9%) in the cohort study. This polymorphism showed a significantly higher percent body fat and higher levels of serum insulin and leptin, compared with wild type and heterozygotes. Our study provided the possibility that polymorphism in the promoter region of the CCK-A receptor gene may be one of genetic factors affecting fat deposition.

Adipose Tissue↗
PubMed2000

A case of monoclonal gammopathy associated with acute myelomonocytic leukemia with eosinophilia suggested to be the result of lineage infidelity.

Acute myelomonocytic leukemia (AMMoL) accompanied by monoclonal gammopathy is a rare condition, and its pathogenesis and the cytogenetic mechanism of such leukemogenesis have not been determined in detail. A case of AMMoL with eosinophilia accompanied by immunoglobulin G kappa monoclonal gammopathy is described. Immunophenotypic studies of the peripheral blood and bone marrow mononuclear cells revealed no evidence of abnormally proliferating cells of B-lineage. DNA analyses of bone marrow mononuclear cells containing leukemic cells revealed rearrangement of the kappa-light chain (Igkappa) gene and c-myc and c-jun proto-oncogenes. The intensities of the rearranged bands for these genes on Southern blot analysis suggested the existence of a major population of leukemic cells with rearranged Igkappa gene and minor population(s) of leukemic cells with rearranged c-myc and/or c-jun proto-oncogene(s) in the patient's bone marrow and indicated the occurrence of genetic evolutionary changes in leukemic cells in this patient before starting chemotherapy. These results suggest that these leukemic cells are the most likely candidate for immunoglobulin G kappa monoclonal protein production, and structural abnormalities of c-myc and c-jun proto-oncogenes may have contributed to the evolution of leukemic cells in this patient.

Blotting, Southern↗
PubMed2000

Dejerine-sottas disease with a novel de novo dominant mutation, Ser 149 Arg, of the peripheral myelin protein 22.

The Ser149Arg mutation of peripheral myelin protein 22 (PMP22) was found in a 19-year-old woman with a sporadic case of Dejerine-Sottas disease. The patient showed delayed motor development. She walked for the first time with support at the age of 2 years. Scoliosis developed at age 4 years. Her walking ability was best at age 11. Thereafter, she showed progressive muscle weakness and sensory disturbances in the distal extremities. At the age of 18 years, the use of a wheelchair became necessary. Motor and sensory nerve conduction studies showed absent motor and sensory responses on electrical stimulation of the limb nerves. A sural nerve biopsy specimen showed marked decreases in the numbers of both large and small myelinated fibers, abundant onion-bulb formation, and hypomyelination. Electron microscopic observation revealed the presence of demyelinated axons and myelin sheaths disproportionately thin relative to axon diameter. That this was a de novo mutation was established by parentage testing and PMP22 gene analysis of the parents. The mutation seems to be novel and dominant.

Adult↗
PubMed1999

Myelinated fibers in Charcot-Marie-Tooth disease type 1B with Arg98His mutation of Po protein.

This study was undertaken to characterize the clinical, electrophysiologic, and histopathologic features of five presumably unrelated Japanese patients with Charcot-Marie-Tooth (CMT) disease type 1B and Arg98His substitution of Po protein and, in particular, to correlate Arg98His substitution to the ultrastructural abnormalities of the myelin sheath. Systematic morphometric studies of the sural nerve, where the CMT type 1B gene abnormality is expressed, have not been performed, especially on the basis of the type of mutation causing CMT type 1B. Electrophysiologic evaluation of limb nerves and morphometric analysis of sural nerves obtained at biopsy were performed. Ultrastructural myelin abnormalities were precisely examined. Clinical symptoms appeared from the second to the fifth decade. All probands presented with gait disturbance. Motor and sensory conduction velocities in the median and ulnar nerves ranged from 10 to 30 m/s. Segmental demyelination and remyelination and marked loss of myelinated fibers were the main findings. On electron microscopy, widening between major dense lines was found between the paired intraperiod lines, where the extramembranous portion of the Po protein resides. This widening is probably directly related to Arg98His substitution. Focal uncompaction of major dense lines coexisted with this widening. This uncompaction, which directly decreases the number of myelin lamellae, may be a secondary effect of Arg98His substitution on the intramembranous domain of Po protein. In conclusion, myelin changes at both extracellular and cytoplasmic appositions of Schwann cell membranes were found in association with Arg98His substitution of Po protein. This study contributes to a better understanding of myelin abnormalities in patients with CMT type 1B and Arg98His or other similar extramembranous amino acid substitutions of Po protein.

Adult↗
PubMed1999

Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: potential inclination to T-lymphoproliferative disease.

To assess the abnormal T-cell expansion in chronic active Epstein-Barr virus infection (CAEBV), T-cell antigen receptor (TCR) repertoire was analyzed in four patients with the disease. All fulfilled the diagnostic criteria of CAEBV, presenting with fever, hepatosplenomegaly, cytopenia, abnormal high titers of anti EBV-antibodies, and positive EBV genome of unknown cause. Southern blotting probed with EBV-terminal repeats and TCR Cbeta gene indicated clonal expansion of the infected cells in 3 and 2 patients, respectively. The number of CD4+ HLA-DR+ cells appreciably increased in patients 1 (59%) and 2 (24%), who had a coronary aneurysm and central nervous system involvement, respectively. TCR gene expression examined by the inverse polymerase chain reaction methods revealed that Vbeta gene usages were preferential in all patients (Vbeta7 and Vbeta12: patient 1, Vbeta4: patient 2, Vbeta13: patients 3 and 4), compared with those in healthy controls. Valpha18 gene expression was remarkably high in patients 1 and 2. Moreover, Jbeta gene expression was skewing in the reigning Vbeta clones in all patients. Vbeta4-Jbeta1.5 and Vbeta13-Jbeta1.5 genes were clonally expressed in patients 2 and 4, respectively. These results suggest that CAEBV is associated with the restricted diversity of T-cells, which may stem from the sustained expansion of oligoclonal T-cells possibly driven by conventional viral antigens, but not, superantigens. Although the study is limited by the small number of patients, the unbalanced T-cell repertoire might contribute to the evolution of T-lymphoproliferative disease, otherwise, imply the innate defective immunity to EBV in CAEBV patients.

Adolescent↗
PubMed1998

Polymorphism of the apolipoprotein E and angiotensin I converting enzyme genes in Japanese patients with myocardial infarction.

OBJECTIVE: To investigate the genetic contribution for myocardial infarction. METHODS: We investigated common polymorphisms of apolipoprotein E gene and angiotensin converting enzyme (ACE) gene in Japanese population. Subjects were 422 healthy people and 254 patients with myocardial infarction. We evaluated the 287 base pair (bp) insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene and a polymorphism in the apolipoprotein E gene by using the polymerase chain reaction. RESULTS: The ACE genotype prevalences for II, ID, and DD were 36.2, 46.1, and 17.7%, respectively, among the myocardial infarction patients. The prevalence of the D allele of the ACE gene among the myocardial infarction patients (0.593) exceeded that among the healthy controls (0.407). The prevalences of the epsilon 2, epsilon 3, and epsilon 4 alleles of the apolipoprotein E genotype among healthy controls were 0.024, 0.882, and 0.094, and those among survivors of myocardial infarction were 0.024, 0.834, and 0.142, respectively. Myocardial infarction patients had an excessive prevalence of the apolipoprotein E epsilon 4 allele (P < 0.05). Multiple regression analysis demonstrated that the independent risk factors for developing myocardial infarction were age, DD genotype of ACE gene, and apolipoprotein E epsilon 4 allele. Stenotic coronary vessels in myocardial infarction patients did not differ significantly among the patients with various ACE and apolipoprotein E genotypes in the present study. CONCLUSIONS: Among the Japanese, apolipoprotein E epsilon 4 carriers and subjects with ACE DD genotype are at an increased risk of myocardial infarction.

Aged↗
PubMed1998

The relatively high frequency of p53 gene mutations in multiple and malignant phaeochromocytomas.

To explore the clinical significance of p53 in the pathogenesis of adrenal neoplasms, we investigated the incidence of p53 gene mutations in functioning human adrenal tumours using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to screen p53 exons 4 to 9. We examined 29 adrenocortical adenomas (primary aldosteronism, n=17; Cushing's syndrome, n=12, all benign), and 33 phaeochromocytomas (benign solitary, n=18; benign multiple, n=5; malignant, n=10) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary phaeochromocytoma tissues. In contrast, six phaeochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands revealed six cases with nine mutations or intronic sequence alterations: three cases contained sequence alterations within intronic regions, three cases with silent mutation (sequence alteration in codon without amino acid alteration), and three cases contained missense mutations (one case each in exons 5, 6 and 9). Immunohistochemical staining demonstrated that two of three cases with missense mutations and one case with an intronic sequence alteration over-expressed p53 protein in tumour cell nuclei. We observed no association between p53 gene mutation and p21/WAF1/Cip-1 expression. The relatively high incidence of p53 gene mutations or intronic sequence alteration in multiple and malignant phaeochromocytomas, but not in benign solitary cases, suggests that p53 mutation could play some role in the pathogenesis of multiple and/or malignant phaeochromocytomas.

Adenoma↗
PubMed1998

[TAL1 gene analysis in T-cell malignancies].

Site-specific recombination of the TAL1 gene was analyzed by Southern blotting and polymerase chain reaction (PCR) in 44 cases of childhood T-cell acute lymphoblastic leukemia (T-ALL), 20 cases of childhood T-cell non-Hodgkin's lymphoma (T-NHL) and 35 cases of adult T-cell malignancies. This recombination was found in 10 (22.7%) of 44 childhood T-ALL patients, but in none of the T-NHL or adult T-cell malignancies. Recombination of the TAL1 gene was therefore suggested to be specific for childhood T-ALL. The immunophenotypic features of the 10 T-ALL patients with this recombination were CD1-, CD2+, CD4-, CD7+, CD10-, and they had a significantly better outcome than other T-ALL cases without the recombination. The PCR technique revealed minimal residual disease (MRD) in 2 patients. One showed persistent MRD, while in the other MRD was recognized only at initial diagnosis. Further investigation is needed whether T-ALL with this recombination constitutes a distinct clinical subgroup among childhood T-ALL patients.

Adolescent↗
PubMed1997

Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype.

OBJECTIVES: To assess the possible relationship between the metabolic disposition of pantoprazole and genetically determined S-mephenytoin 4'-hydroxylation phenotype and genotype. METHODS: The pharmacokinetic disposition of pantoprazole was investigated in 14 Japanese male volunteers (seven extensive and seven poor metabolizers of S-mephenytoin). All subjects received a single 40 mg oral dose of pantoprazole as the enteric-coated formulation. RESULTS: An interphenotypic difference in the metabolic disposition of pantoprazole was observed: the mean values for area under the concentration-time curve (AUC), elimination half-life (t1/2), and apparent oral clearance were significantly (p < 0.01) greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean AUC of pantoprazole sulfone was greater (p < 0.01) in the poor metabolizers than in the extensive metabolizers, whereas the mean AUC of the main demethylated metabolite (M2) was lower (p < 0.01) in the poor metabolizers than in the extensive metabolizers. A significant negative correlation was observed between the individual values for log10% urinary excretion of 4'-hydroxymephenytoin and AUC of pantoprazole (rs = -0.816; p < 0.005). The CYP2C19 genotyping test results were found to be in a complete accordance with the phenotypes. CONCLUSION: These data indicated that the metabolic disposition of pantoprazole is under the pharmacogenetic control of S-mephenytoin 4'-hydroxylase (CYP2C19).

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

De novo mutation (Arg98-->Cys) of the myelin P0 gene and uncompaction of the major dense line of the myelin sheath in a severe variant of Charcot-Marie-Tooth disease type 1B.

A point mutation (Arg98-->Cys) of exon 3 coding for the extracellular domain of the myelin protein zero (P0) gene was found in a sporadic case of an eighteen year old Japanese man with a severe variant of Charcot-Marie-Tooth disease type 1B (CMT1B). A de novo mutation was established by parentage testing and analyses of the P0 gene in the family. This patient showed delayed motor development, nonprogressive limb weakness and kyphoscoliosis. In addition to the nerve biopsy findings typical of CMT1B, such as segmental demyelination, marked decrease in the density of myelinated fibers, and frequent onion-bulb formation, ultrastructural examination disclosed uncompaction of the major dense lines with slight widening of the intraperiod distance in the inner layers of the myelin sheath. Although mutations in the extracellular domain of P0 should affect homophilic adhesion between external surfaces of Schwann cell processes, resulting in the separation at the intraperiod lines, our study shows uncompacted major dense lines as a main myelin abnormality where the cytoplasmic domain of P0 resides.

Adolescent↗
PubMed1997

Localized diffuse large-cell lymphoma possibly coated with anti-tumor autoantibody: kappa lambda-dual-positive lymphoma.

We report a case of diffuse large-cell lymphoma which pursued a clinically indolent course while remaining untreated. The tumor cells expressed surface IgG, CD10, CD19 and CD20, but not surface IgM, IgD, IgA, CD5, CD16, CD32 and CD64. In addition, these cells appeared to coexpress kappa- and lambda-light chains on their surface. JH and J lambda genes were monoclonally rearranged, but not the J kappa gene. The present lymphoma was found to have arisen from follicle center cells expressing IgG lambda, while the surface kappa-light chain seemed to be extrinsic. Furthermore, the extrinsic immunoglobulin bearing the kappa-light chain may have belonged to IgG because no surface immunoglobulins other than IgG were detected on the cell surface. Then, the extrinsic IgG may have combined with certain molecules on the tumor-cell surface through its Fab portion because the tumor cells lacked all three receptors for the IgG-Fe portion. Fc gamma RI (CD64). Fc gamma RII (CD32) and Fc gamma RIII (CD16). From these findings and the patient's history of never having received a blood transfusion, we concluded that the present case might be of a B-cell lymphoma possibly coated with an IgG-type autoantibody which appeared to have anti-idiotypic activity.

Adult↗
PubMed1997

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features.

p16 and p15 genes are putative tumor suppressor genes located on chromosome 9p21. In acute leukemias, alterations of p16 and p15 genes have been reported to occur exclusively in lymphoid lineage. We analyzed alterations of p16 and p15 genes in 46 acute leukemias with MLL gene rearrangements by Southern blot analysis, and investigated the association with clinical characteristics. We identified homozygous deletion of p16 and p15 genes in five (19%) of 27 acute lymphoblastic leukemias (ALLs) and in two (11%) of 19 acute myeloid leukemias (AMLs). Patients with homozygous deletion of p16 and p15 genes showed higher average leukocyte counts (343 x 10(9)/l vs 271 x 10(9)/l) and lower estimated 2-year survival rates than those with normal p16 and p15 genes (14.3 vs 30.7%), although the differences were not statistically significant. In addition, we investigated mutation of p16 gene by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 31 patients, but no mutation was found in the patients tested. Our results suggest that alterations of p16 and p15 genes are involved in a subset of acute leukemias with MLL gene rearrangement not only of lymphoid but also of myeloid phenotype. Homozygous deletion of p16 and p15 genes may be a possible adverse prognostic factor, although further analysis would be needed to confirm it.

Adolescent↗