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Biomedical subjects

M Takata

Publications and source records attributed to M Takata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Phenotypic expression of colorectal adenocarcinomas with reference to tumor development and biological behavior.

The purpose of this study is to clarify the correlation between cell differentiation and tumor development, including tumor aggressiveness and biological behavior. Eighty-three cases of advanced colorectal adenocarcinoma were randomly selected. Using immunohistochemical staining with antibodies to CD10, MUC2 and human gastric mucin (HGM), the colorectal adenocarcinomas could be classified into five types (18 small intestinal, 27 large intestinal, 2 gastric, 9 mixed and 27 unclassified). Each type had characteristic features. The small-intestinal type showed a relatively lower incidence of lymphatic permeation and higher venous invasion. The large-intestinal type showed a low incidence of venous invasion and lymph node metastasis. The mixed type revealed female and right-side-dominant distribution, large tumor size, high incidence of mucinous carcinoma, and low incidence of venous invasion. Gastric type was seen in only two cases (2%), which exhibited high histologic grade, lymphatic permeation and lymph node metastasis with no venous invasion. Such phenotypic classifications are considered to be useful not only for evaluation of the biological behavior of the carcinoma, but also for analysis of tumorigenesis.

Adenocarcinoma↗
PubMed2001

Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs.

The Rad51 protein, a eukaryotic homologue of Escherichia coli RecA, plays a central role in both mitotic and meiotic homologous DNA recombination (HR) in Saccharomyces cerevisiae and is essential for the proliferation of vertebrate cells. Five vertebrate genes, RAD51B, -C, and -D and XRCC2 and -3, are implicated in HR on the basis of their sequence similarity to Rad51 (Rad51 paralogs). We generated mutants deficient in each of these proteins in the chicken B-lymphocyte DT40 cell line and report here the comparison of four new mutants and their complemented derivatives with our previously reported rad51b mutant. The Rad51 paralog mutations all impair HR, as measured by targeted integration and sister chromatid exchange. Remarkably, the mutant cell lines all exhibit very similar phenotypes: spontaneous chromosomal aberrations, high sensitivity to killing by cross-linking agents (mitomycin C and cisplatin), mild sensitivity to gamma rays, and significantly attenuated Rad51 focus formation during recombinational repair after exposure to gamma rays. Moreover, all mutants show partial correction of resistance to DNA damage by overexpression of human Rad51. We conclude that the Rad51 paralogs participate in repair as a functional unit that facilitates the action of Rad51 in HR.

Animals↗
PubMed2001

Cytokines decrease sGC in pulmonary artery smooth muscle cells via NO-dependent and NO-independent mechanisms.

Exposure of rat pulmonary artery smooth muscle cells (rPASMC) to cytokines leads to nitric oxide (NO) production by NO synthase 2 (NOS2). NO stimulates cGMP synthesis by soluble guanylate cyclase (sGC), a heterodimer composed of alpha(1)- and beta(1)-subunits. Prolonged exposure of rPASMC to NO decreases sGC subunit mRNA and protein levels. The objective of this study was to determine whether levels of NO produced endogenously by NOS2 are sufficient to decrease sGC expression in rPASMC. Interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) increased NOS2 mRNA levels and decreased sGC subunit mRNA levels. Exposure of rPASMC to IL-1beta and TNF-alpha for 24 h decreased sGC subunit protein levels and NO-stimulated sGC enzyme activity. L-N(6)-(1-iminoethyl)lysine (NOS2 inhibitor) or 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (sGC inhibitor) partially prevented the cytokine-mediated decrease in sGC subunit mRNA levels. However, cytokines also decreased sGC subunit mRNA levels in PASMC derived from NOS2-deficient mice. These results demonstrate that levels of NO and cGMP produced in cytokine-exposed PASMC are sufficient to decrease sGC subunit mRNA levels. In addition, cytokines can decrease sGC subunit mRNA levels via NO-independent mechanisms.

Animals↗
PubMed2001

[All-trans retinoic acid combined with low-dose cytosine arabinoside treatment for acute myelogenous leukemia with trilineage myelodysplasia--a case report].

AML with trilineage myelodysplasia (AML/TMDS) is recognized as having of poor prognosis due to its resistance to chemotherapy in comparison with de novo AML. An AML/TMDS patient who failed to respond to ordinary induction therapy achieved complete remission with combination therapy consisting of all-trans retinoic acid (ATRA) and low-dose Ara-C. No serious toxicity was observed. ATRA combined with low-dose Ara-C could be an alternative treatment for this kind of patient.

Antimetabolites, Antineoplastic↗
PubMed2001

Focal segmental glomerulosclerosis associated with acromegaly.

Experimental studies in rats have demonstrated an association between focal segmental glomerulosclerosis (FSGS) and growth hormone, but patients with FSGS complicating acromegaly are very rare. In this report we present a case of FSGS associated with acromegaly. With a long history of soft tissue swelling of hands and feet, elevated plasma growth hormone levels and other biochemical abnormalities, a 53-year old male had suffered from acromegaly for over 15 years. He had moderate proteinuria for 6 years, but never evidenced nephrotic syndrome. A renal biopsy specimen revealed FSGS and glomerular hypertrophy. Trans-sphenoidal surgical removal of the pituitary adenoma resulted in the normalization of elevated growth hormone and insulin-like growth factor I levels, but proteinuria continued. This case suggests that the overproduction of growth hormone may participate, at least in part, in the development of human FSGS. It is possible that once FSGS is present in an acromegalic patient, cessation of GH overproduction may not be enough to reverse it.

Acromegaly↗
PubMed2000

Covalent bonds in AlMnSi icosahedral quasicrystalline approximant

Electron density distributions were obtained using the maximum entropy method with synchrotron radiation powder data. In the metallic Al12Re, metallic bonding was observed for the icosahedral Al12 cluster with central Re atom. In the nonmetallic alpha-AlMnSi 1/1 approximant, covalent bonds were found in the electron density distribution of the Mackay icosahedral cluster without central atom. Rather than the Hume-Rothery mechanism, the covalency of Al (Si) icosahedron and that between Al (Si) and Mn atoms is considered to be the origin of the pseudogap and nonmetallic behavior of alpha-AlMnSi.

Journal Article↗
PubMed2000

Clonal heterogeneity in sporadic melanomas as revealed by loss-of-heterozygosity analysis.

The major obstacle preventing effective treatment of melanoma is the biological heterogeneity of tumor cells. This study was performed to determine clonal genetic heterogeneity within primary melanoma and the evolution of these heterogeneous sub-clones during disease progression. DNA samples were obtained from 44 morphologically distinct areas identified within 10 primary tumors and from 15 metastases in the same patients. Loss of heterozygosity (LOH) analyses were performed using 17 microsatellite markers that mapped to chromosomes 6q, 9p, 10q and 18q, the most frequently deleted in melanoma. Of 10 primary tumors, 8 were revealed to have intratumoral genetic heterogeneity in terms of LOH of the 4 chromosome arms examined, 7 containing at least 2 different sub-clones harboring LOH of different chromosome areas, while the remaining one tumor showed prominent intratumoral genetic heterogeneity consisting of at least 6 genetically distinct sub-clones. LOH of 6q was detected only in a sub-set of multiple microdissected samples in most of the primary tumors, but was most frequently detected in metastases, suggesting that loss of this chromosome arm occurred late and played an important part in metastatic progression. Comparison of LOH between sub-clones within primary tumors and within metastases showed the divergence of metastatic clones from dominant populations within the primary tumor in 5 patients, whereas in the remaining three patients parent sub-clones were not identified, or constituted only a minor sub-population within the primary tumors. These results, showing considerable genetic heterogeneity in sporadic melanoma, have profound implications for the choice of future therapeutic strategies.

Adult↗
PubMed2000

Iodine absorption after intraoperative bowel irrigation with povidone-iodine.

PURPOSE: Povidone-iodine is a commonly used intrarectal tumoricidal agent in patients undergoing colorectal surgery. The aim of this study was to assess systemic absorption of total iodine and its effect on thyroid function after intrarectal application. METHODS: Twenty patients with carcinoma of the rectum received intraoperative irrigation with either povidone-iodine (Group A; n = 10) or physiologic saline (Group B; n = 10). Ten patients with carcinoma of the sigmoid colon (group C) were treated the same as Group A. Electrolyte, total iodine, triiodothyronine, thyroxine, and thyroid-stimulating hormone values were measured in serum preoperatively and before intraoperative irrigation and immediately, ten minutes, 1 hour, 6 hours, 24 hours, and two weeks after irrigation. RESULTS: No significant changes occurred in serum electrolytes. A significant uptake of the total iodine was demonstrated in each group. Total iodine levels examined immediately, ten minutes, and one hour after irrigation in Group C were significantly higher than those examined in Group B. Maximum values were obtained one hour after irrigation in Groups A and B and six hours after irrigation in Group C. No significant changes occurred in triiodothyronine, thyroxine, and thyroid-stimulating hormone levels among the three groups. The decrease in triiodothyronine levels after surgery was demonstrated in each group. We noted a decrease after surgery in thyroxine levels for Groups A and B and in thyroid-stimulating hormone levels for Group B. Those hormones were not affected by the administration of povidone-iodine. CONCLUSION: High serum levels of iodine did not cause organ toxicity, suggesting that a single use of intraoperative bowel irrigation with povidone-iodine may be performed with practically negligible risk.

Adult↗
PubMed2000

Evolution of and obstacles in surgical treatment for hepatocellular carcinoma over the last 25 years: differences over four treatment eras.

This study was designed to clarify what differences the last 25 years have made in surgical results for patients with hepatocellular carcinoma (HCC). We examined results for 716 hepatectomized patients in four treatment eras: first era (1973-1980; n = 58), second era (1981-1985; n = 155), third era (1986-1990; n = 243), and fourth era (1991-1997; n = 260). Patient background, tumor characteristics, type of hepatectomy, treatment for intrahepatic recurrences, and surgical results in the four eras were compared by univariate analysis to clarify the factors that have contributed to or impeded progress in the surgical treatment of HCC. Although there were no significant chronological differences in liver pathology and surgical resectability, operative mortality was reduced to 2% in the fourth era, from 29% in the first era. With an increasing proportion of early-stage HCCs (TNM, stages I and II), the cumulative survival rate at 5 years improved in the course of the eras in our overall population of patients (12%, 31%, 38%, and 51%, respectively, for the first, second, third, and fourth eras) and in a subset of the population divided according to tumor stage. Also, we found a chronological improvement in the survival rate at 3 years after intrahepatic recurrence (10%, 28%, 36%, and 44%, respectively in the first second, third, and fourth eras). This improvement was associated with the establishment of an early detection program for intrahepatic recurrences. However, the recurrence rate was similar in any subset of the population through the four eras. Although this univariate study could not determine independent factors that contributed to the chronological progress in results for HCC surgery in the four eras, it is conceivable that the establishment of indication criteria for hepatectomy, an early detection program for primary and recurrent lesions, and the introduction of multimodal treatment for recurrence were contributory factors in this improvement. A strategy for alleviating the frequent recurrences originating from posthepatectomy metachronous carcinogenesis remains to be established.

Analysis of Variance↗
PubMed2000

Genetic changes in sweat gland carcinomas.

The molecular pathogenesis of malignant appendageal tumors is poorly understood. Immunohistochemical staining, polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) and sequencing analyses were performed in a mixed group of 21 sweat gland carcinomas. LOH was mostly confined to the chromosome arm 17p. None of the remaining 17 tumors showed LOH at any loci. Nuclear accumulation of p53 protein was observed in 3 tumors, all of which also showed LOH of 17p. One eccrine gland adenocarcinoma showed allelic loss of 17p and a Cys 176 Arg mutation in the p53 gene. The other three tumors that showed LOH of 17p, however, had wild-type p53 genes. A clear transition from benign eccrine poroma to porocarcinoma that was associated with p53 protein stabilization and allelic loss was observed in one tumor. One eccrine porocarcinoma/undifferentiated adnexal carcinoma showed prominent microsatellite instability, probably reflecting an underlying defect in DNA mismatch repair. Overexpression of erbB-2 was observed in three tumors. The low frequencies of LOH and p53 alterations in sweat gland carcinomas contrasted with the multiple genetic defects normally observed in cutaneous squamous cell carcinomas, and may be partly explained by the relative protection of cutaneous appendages from ultraviolet light and other environmental mutagens.

Adenocarcinoma↗
PubMed2000

Regulation of the phospholipase C-gamma2 pathway in B cells.

In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B-cell antigen receptor (BCR), with different extents of receptor engagement leading to such outcomes as cell death, survival, or proliferation. Here, based upon the available genetic and biochemical data of the BCR signal components, we discuss several mechanisms by which BCR signals are propagated and modified, with specific emphasis on the phospholipase C (PLC)-gamma2-calcium pathway Gene-targeting experiments in DT40 chicken B cells highlighted the importance of the intracellular protein tyrosine kinases Syk and Btk in PLC-gamma2 activation. Until recently, the molecular mechanism underlying the double requirement for Syk and Btk in PLC-gamma2 activation remained unclear, but new data suggest that an adapter molecule, B-cell linker protein (alternatively named SLP-65 or BASH), phosphorylated by Syk, provides docking sites for Btk SH2 domain as well as PLC-gamma2 SH2 domains, thus bringing Btk into close proximity with PLC-gamma2. The activated Btk then phosphorylates PLC-gamma2, leading to its activation. The activated PLC-gamma2 converts phosphatidylinositol 4,5-bisphosphate into the second messenger inositol 1,4,5-trisphosphate (IP3), which in turn binds to IP3 receptors located on the endoplasmic reticulum (ER). Binding of IP3 to the IP3 receptors is essential for triggering a calcium release from the ER and subsequent entry of extracellular calcium. Balancing these activation signals in the PLC-gamma2-calcium pathway are the inhibitory receptors expressed on B cells, FcyRII and paired immunoglobin-like receptor (PIR)-B. Although both FcyRII and PIR-B inhibits the BCR-mediated [Ca2+]i increase, the inhibitory mechanisms of these receptors are distinct. The FcyRII-mediated inhibitory signal is dependent on lipid phosphatase SHIP, whereas the PIR-B requires redundant functions of protein phosphatases SHP-1 and SHP-2. Thus, PIR-B and FcgammaRII inhibit calcium signals by utilizing two distinct signaling molecules, thereby contributing to setting threshold levels for activation signals as well as terminating activation responses.

Animals↗
PubMed2000

Expression of structurally unaltered androgen receptor in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is an uncommon neoplasm of the skin that shows differentiation to an apocrine sweat gland. Although we previously showed that erbB-2 overexpression may play a part in the progression of EMPD, molecular genetic defects underlying the development of EMPD are poorly understood. In the study described here, we examined androgen receptor expression and gene alterations in 30 cases of EMPD without internal malignancy. Immunohistochemistry revealed that 24 of 30 (80%) cases of EMPD variably expressed nuclear androgen receptor. Semi-quantitation of receptor content by scoring immunostained sections showed no difference between in situ (n = 17) and invasive (n = 13) EMPD tumors. Androgen receptor expression was also observed in four of six lymph node metastases. In these lymph nodes, expression of androgen receptor mRNA was confirmed by reverse transcriptase-polymerase chain reaction. Direct sequencing of exon 2 through exon 8, which encodes DNA- and hormone-binding domains of the androgen receptor gene, revealed no mutation in any of the 10 advanced stage tumors. Neither amplification nor deletion of the androgen receptor gene locus was detected by dual color fluorescence in situ hybridization analysis in 14 tumors. The present findings showing frequent expression of structurally unaltered androgen receptor in an advanced stage of EMPD may provide a rational basis for hormone therapy, which is widely used in the treatment of metastatic prostate cancer and androgen receptor-positive breast cancer recurrence.

Aged↗
PubMed2000

The temporal and spatial distribution of p21WAF expression in skin appendages.

p21WAF is a cyclin-dependent kinase inhibitor which is widely expressed in epidermal structures. Using a combination of double immunocytochemical staining and combined in situ hybridization, we show that there is a striking exclusivity between the expression of Ki67 and p21WAF in the hair matrix. Some cells that are Ki67-positive also express p53, but as they exit the cell cycle they assume p21WAF-positive/p53-negative status. By contrast, cells in the interfollicular epidermis of psoriatic lesions, in the sebaceous gland, and in the outer root sheath are p21WAF-positive/p53-positive but Ki67-negative. These results suggest that in some anatomical parts of the epidermis, p21WAF expression can accompany p53 expression, whereas in other parts, the expression of these markers is reciprocal, suggesting that other pathways may be controlling p21WAF expression. In order to define, functionally, the presence of p53-independent p21WAF expression in skin, we examined lesions of Bowen's disease in which both alleles of p53 were inactivated. p21WAF expression was still observed, confirming a role for p53-independent expression of p21WAF in human skin in vivo.

Bowen's Disease↗
PubMed2000

Hereditary non-polyposis colorectal cancer associated with disseminated superficial porokeratosis. Microsatellite instability in skin tumours.

A 73-year-old man presented with typical lesions of disseminated superficial porokeratosis (DSP) and multiple seborrhoeic keratoses on his face, trunk and extremities, and later developed a keratoacanthoma on his lip. He belonged to a cancer-prone pedigree susceptible to colonic, uterine and other internal cancers, and had a personal history of early gastric cancer and advanced adenocarcinoma of the descending colon without adenomatous polyps at age 59 years. Polymerase chain reaction amplification of skin samples for seven separate microsatellite polymorphisms revealed microsatellite instability (MSI) at multiple loci in five of six seborrhoeic keratoses and the keratoacanthoma, strongly suggesting underlying defects in DNA mismatch repair. Although no germline mutations in two mismatch repair genes hMSH2 and hMLH1 were found, our patient was recognized as having hereditary non-polyposis colorectal cancer (HNPCC) based on the family history and the findings of the microsatellite analysis of skin tumours. This confirmed the usefulness of detection of MSI in prevalent and readily accessible skin lesions, including non-sebaceous non-dysplastic tumours such as seborrhoeic keratosis in the screening of HNPCC families. Although DSP may also be inherited as an autosomal dominant condition, this particular skin disease appeared to be sporadic in our patient and, to our knowledge, no association of DSP or other forms of porokeratosis with HNPCC has previously been reported. In contrast to the seborrhoeic keratoses and keratoacanthoma, no MSI was observed in two samples from DSP lesional epidermis examined.

Adult↗
PubMed2000

SHP-1/immunoreceptor tyrosine-based inhibition motif-independent inhibitory signalling through murine natural killer cell receptor Ly-49A in a transfected B-cell line.

Ly-49A is a member of the Ly-49 family of mouse natural killer cell receptors that inhibit cytotoxicity upon recognition of their ligands, the major histocompatibility complex (MHC) class I molecules, on the target cell surface. Although Ly-49A has an immunoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail, relatively little is known about the mechanisms underlying its inhibitory function. We report here that antibody-mediated co-ligation of the B-cell receptor (BCR) with the transfected Ly-49A molecule results in abrogation of BCR-induced interleukin-2 (IL-2) secretion and mild reduction in activation of Erk1/2 and p38 mitogen-activated protein (MAP) kinases in the B-cell line A20. Surprisingly, BCR-induced calcium mobilization was unaffected by cross-linking of BCR with Ly-49A. Furthermore, substitution of the single tyrosine residue in ITIM with phenylalanine, did not result in a complete loss of inhibitory function, as measured by BCR-induced IL-2 secretion. Deletion of the N-terminal 37 amino acid peptide, which includes the ITIM, did abrogate the inhibitory activity. Co-immunoprecipitation experiments revealed that, upon induction of tyrosine phosphorylation, Ly-49A recruits tyrosine phosphatase src-homology 2 (SH2) containing tyrosine phosphatases-1 (SHP-1), but not inositol phosphatase src-homology 2 (SH2) containing inositol phosphatase (SHIP), and that the tyrosine residue in the ITIM is critical for this interaction. These results suggest that transfected Ly-49A utilizes two different inhibitory mechanisms in B-cell signalling: ITIM-dependent and ITIM-independent.

Animals↗