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A Tamura

Publications and source records attributed to A Tamura.

At least 73 records · Page 4Linked to original sources

Immunohistochemical study of tyrosine phosphorylation signaling in the involuted thymus.

Thymic involution has been reported to be an important parameter of the degree and duration of child abuse. In the present study, we assessed the status of tyrosine phosphorylation signaling, which is known to play a key role in the physiological function of the thymus, in involuted thymuses of abused children through immunohistological studies performed with anti-phosphotyrosine antibodies. We found that tyrosine-phosphorylated proteins were present in high amounts in Hassall's corpuscles (HC) in the medulla of control thymuses. In involuted thymuses of abused children, expression of tyrosine-phosphorylated proteins was reduced with accompanying morphological changes of HC, such as reduction in size or calcification. These findings lead us to the suggestion that tyrosine phosphorylation signaling is reduced in involuted thymuses of abused children and that reduction of the signaling may be associated with morphological changes of HC as observed in involuted thymuses of abused children. In order to certify the suggestion, we investigated expression of tyrosine-phosphorylated proteins in involuted thymuses of stressed rats as well as in control thymuses. Immunohistochemistry revealed that tyrosine-phosphorylated proteins were expressed in control thymuses, more abundantly in the medulla, and reduced remarkably in involuted thymuses of stressed rats. Further, immunoblot analysis also showed that expression of phosphotyrosine-containing proteins was reduced in thymus extracts of involuted thymuses of stressed rats, thus supporting the suggestion. Our results also raise the possibility that components of tyrosine phosphorylation signaling could be a molecular marker for thymic involution.

Animals↗

Reduction of tyrosine-phosphorylated proteins in involuted thymuses of stressed rats: a study using immunological methods.

In the present study, we investigated whether tyrosine phosphorylation was involved in thymic involution, which has been reported to correlate well with the effects of various kinds of stresses. Immunohistochemistry using the anti-phosphotyrosine antibody showed that the immunoreactivity decreased remarkably in the involuted thymus of stressed rats as compared with the control thymus. Immunoblot analysis using the anti-phosphotyrosine antibody revealed the tyrosine-phosphorylated proteins with apparent molecular masses of 120, 90, and 70 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis were detected in the control thymus. The immunoreactive band corresponding to the three proteins decreased remarkably in the involuted thymus. Further, we found by immunoprecipitation experiments that the 120 kDa protein was p130cas, a crk-associated src substrate. These findings suggest that tyrosine phosphorylation signaling may be involved in thymic involution.

Animals↗

Sphingolipid biosynthesis by L-PDMP after rat MCA occlusion.

L-PDMP (L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

Animals↗

Expression of the janus kinases-signal transducers and activators of transcription pathway in Hassall's corpuscles of the human thymus.

The janus kinases (JAK) and signal transducers and activators of transcription (STAT) pathway has been shown to play a key role in cytokine-mediated signal transduction, and to regulate growth, differentiation, and death of both normal and transformed cells. In the present study, we investigated immunohistochemically the distribution of the JAK-STAT pathway in the human thymus. Various elements of the pathway were abundantly expressed in Hassall's corpuscles, located in the thymus medulla and representing terminal stages of the thymic medullary epithelium. Furthermore, the elements of the pathway showed distinct localization in Hassall's corpuscles. JAK1, JAK2, and TYK2 were expressed in high amounts in the entirety of Hassall's corpuscles, whereas JAK3 was in the outer layer. STAT1, STAT2, and STAT6 were abundantly expressed in the entire Hassall's corpuscles, whereas STAT5 was in the outer layer. These findings strongly suggest that the JAK-STAT pathway may play a role in thymic medullary epithelial maturation.

Child, Preschool↗

Immunolocalization of calcineurin and FKBP12, the FK506-binding protein, in Hassall's corpuscles of human thymus and epidermis.

Calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, plays an important role in various physiological functions including T cell activation. This enzyme is a target molecule for the immunosuppressants, cyclosporin A and FK506. In the present study, we investigated immunohistochemical localization of calcineurin and FKBP12, an FK506-binding protein, in human thymus and epidermis. The catalytic subunit (calcineurin A) of calcineurin was abundantly expressed in Hassall's corpuscles which were localized in the thymic medulla and represented the terminal stages of thymic medullary epithelium. The regulatory subunit (calcineurin B) of calcineurin was also expressed in high amounts in Hassall's corpuscles. In the epidermis, which shows similarities to Hassall's corpuscles, both subunits were also abundantly expressed, and their expression increased with the differentiation of keratinocytes. FKBP12 was observed to be expressed abundantly, both in Hassall's corpuscles and the entire epidermis. These findings suggest that the differentiated forms of the two cell types, which are the thymic medullary epithelial cell and the keratinocyte, are the target for pharmacological actions of FK506.

Calcineurin↗

Detection of t(14; 18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease.

The most frequent nonrandom chromosome rearrangements in B-cell non-Hodgkin lymphoma (NHL) is the t(14;18)(q32;q21) found in follicular lymphomas. The t(14;18) in Hodgkin disease (HD) was rarely observed using cytogenetic techniques. Although Southern blot analysis failed to demonstrate the t(14;18), there have been conflicting reports concerning the occurrence of the translocation using polymerase chain reaction (PCR) methods in HD. In some HD tissues, the translocation might be derived from background lymphocytes rather than Hodgkin and Reed-Sternberg (HRS) cells, because B-cells with t(14;18) are regularly generated in normal individuals. However, the cells bearing the translocation have remained unidentified. We describe a patient with HD who showed t(14;18) in hyperdiploid cells using fluorescence in situ hybridization (FISH) and HRS cells which were strongly positive for BCL2 by immunohistochemistry. These findings suggest that HRS cells may have a t(14;18).

Adult↗

Interphase detection of t(4;14)(p16.3;q32.3) by in situ hybridization and FGFR3 overexpression in plasma cell malignancies.

The immunoglobulin (Ig) genes are frequently involved in chromosomal rearrangements with a wide variety of partner loci in multiple myeloma (MM). However, several partner chromosomes have not been detected by conventional cytogenetic methods; for example, 4p16.3 (FGFR3), 6p25.3 (IRF4), and 16q23 (c-maf). To clarify the incidence of t(4;14)(p16.3;q32.3) in primary tumors of MM and to evaluate possible correlations with specific manifestations of the disease, G-banding, double-color fluorescence in situ hybridization (DC-FISH), and/or reverse-transcriptase polymerase chain reaction (RT-PCR) were performed on 40 patients with MM-two with plasmacytoma (PCM) and three with plasma cell leukemia (PCL). All patients were studied by DC-FISH; 40 were studied by G-banding and 36 were studied by RT-PCR. The FISH probes consisted of a cosmid pC385.12 containing the FGFR3 gene, a YAC Y6 containing VH, and a phage Iggamma1-10 containing the gamma1 constant region (Cgamma). We identified eight patients with either FGFR3/Cgamma fusion or FGFR3 overexpression: six patients with both FGFR3/Cgamma fusion and FGFR3 overexpression, one patient with FGFR3/Cgamma, and one with FGFR3 overexpression. FGFR3/Cgamma fusion was demonstrated at a frequency of 19% to 38% on interphase nuclei in seven of the 45 patients. Lytic bone lesions were found to be associated with FGFR3 overexpression. Interphase FISH with FGFR3 and Cgamma probes combined with RT-PCR proved to be an effective tool for detection of this fully cryptic translocation, thus facilitating the characterization of clinical features of MM patients with t(4;14).

Adult↗

Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene.

We report here a 65-year-old man with a myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. He had received chemotherapy with tegafur for renal carcinoma. Chromosome analysis of bone marrow cells revealed complex karyotypes; del(5)(q13) was observed in all 20 metaphase spreads, and two related aberrations, add(12)(p11) and add(12)(p13), were detected in 13 and 7 cells, respectively. Fluorescence in situ hybridization (FISH) analysis with chromosome-specific DNAs revealed that these alterations originated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q13), add(12)(p11), and add(12)(p13) were revised as der(5)t(5;12)(q13;p13), der(12)del(12)(p11p13)t(5;12)(q13;p13), and der(12)t(5;12)(q13;p13), respectively. Fluorescence in situ hybridization with a series of cosmid probes spanning the ETV6 gene showed that the 12p13 breakpoint on the der(12)t(5;12)(q13;p13) was located in intron 1, but the exon 1 signal was deleted. Our results suggest that a fusion gene was generated between the 5'-end of an unidentified partner at 5q13 and the 3'-end of ETV6 by t(5;12)(q13;p13), and that the interstitial deletion (12)(p11p13) occurred following t(5;12) during clonal evolution. del(12)(p11p13), including the rearranged ETV6 gene, may be implicated in the progression of MDS.

Aged↗

CP6679, a new injectable cephalosporin. Part 1: synthesis and structure-activity relationships.

A series of cephalosporins bearing a 5,5-fused ring system, an (imidazo[5,1-b]thiazolium-6-yl)methyl group, at the C-3 position were synthesized and evaluated for in vitro antibacterial activities. CP6679 (1s) and its analogues showed potent antibacterial activities against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. They were also highly active against methicillin-resistant Staphylococcus aureus (MRSA). CP6679 (1s) showed more potent antibacterial activity than ceftazidime (CAZ) or cefpirome (CPR) against Pseudomonas aeruginosa and MRSA.

Ceftazidime↗

Sibling incest and formulation of paternity probability: case report.

Paternity determination of a fetus whose mother was admitted to an institution for the welfare and health of handicapped persons was requested of us by a doctor and lawyer of the institution. The fetus was recovered by a legal artificial abortion based on the Act on Maternity Health and Welfare (Japan) with the permission of the custodian. Commercially available MCT118, HLADQA, PM, and 9 STRs were tested for DNA samples from the fetus, the mother, her younger brother, her father, her grandfather, and 4 staff members of the institution. Only the brother was not excluded and the paternity probability was estimated at 99.857% on the basis of newly formulated expressions for multiallelic loci on the assumption of sibling incest. We concluded then that the fetus was fathered by the brother. DNA fingerprinting with multilocus and single locus minisatellite probes which were performed to confirm the paternity also support the conclusion. Bandsharing frequencies between the family members, however, did not necessarily reflect their actual kinship, which findings suggest that multilocus DNA fingerprinting requires further accumulation of data for consanguineous cases such as incest. Universal formulation for calculating paternity probability for a sibling incest case on the basis of multiallelic monolocus polymorphisms is also presented.

Journal Article↗

Tufted angioma (angioblastoma): case report and review of 41 cases in the Japanese literature.

We report a 53-year-old man with a 2-year history of a violaceous indurated plaque on the shoulder. Although angiosarcoma was clinically suspected, histological examination revealed numerous lobules ('tufts') with cleft-like vascular lumina throughout the dermis and subcutaneous tissue. Tumour cells had no nuclear atypia and were positive for CD34, but almost negative for factor VIII-related antigen. These findings were compatible with a diagnosis of tufted angioma, or angioblastoma. We reviewed 41 cases reported in Japan and found that, although most patients presented during the first year of life (23/41), the condition does occur throughout childhood and adult life. Both sexes are affected equally and, contrary to some reports, it is unlikely that oestrogens have a pathogenic role.

Aged↗

Unfavorable lipid profiles in mild obesity with excess body fat percentage.

BACKGROUND: The aim of the present study was to investigate the usefulness of subclassifications of overweight children using the body fat percentage (Fat%) to predict the serum lipid profile. METHODS: School children (431, 236 boys and 195 girls) aged 9-12 years were divided into three obesity groups (non-, mild and advanced obesity) and were further divided into two subgroups according to the Fat% measured by bioelectrical impedance analysis. The mean fasting serum lipid levels were also evaluated. RESULTS: In the non-obesity and the advanced obesity groups, the Fat%-based subclassification demonstrated no essential differences in lipid profiles or in the prevalence of hyperlipidemia between the two subgroups. However, in the mild obesity group, the levels of low-density lipoprotein cholesterol and triglyceride and the atherogenic index were significantly higher and the high-density lipoprotein cholesterol level was significantly lower in the adipositic subgroup (Fat% > or = age/sex-specific cut-off value) than in the non-adipositic subgroup. Multiple comparison of lipid levels among all six categories of children indicated that the adipositic subgroup of mild obesity had no advantage over the advanced obesity group with respect to the atherogenic potential and that the non-adipositic subgroup of mild obesity showed no additional risks compared to the non-obesity group. Moreover, the prevalence of hyperlipidemia in the adipositic subgroup of mild obesity (50.0%) was significantly different from that in its non-adipositic counterpart (13.3%) and was equivalent to that in the advanced obesity group. CONCLUSIONS: These results suggest that Fat% evaluation is useful to divide mildly obese children into two distinct subtypes based on serum lipid profiles and that the excess Fat% in mildly obese school children is a predictor of atherogenesis.

Adipose Tissue↗