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Biomedical subjects

T Tsujimura

Publications and source records attributed to T Tsujimura.

At least 73 records · Page 4Linked to original sources

Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders.

The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied in the thyroid tissue of various thyroid disorders by an immunohistochemical technique. The concentrations of both SODs in those tissues were measured also by a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were identified by immunocytochemical staining in most cases of papillary carcinoma and in some cases of other thyroid disorders. In normal follicular cells this enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD stained strongly in papillary carcinoma and papillary-growing cells in the thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn-SOD in thyroid tumor tissues and hyperplastic follicular disorders were significantly higher than those in normal thyroid tissue when they were compared as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for other thyroid disorders as compared with that in the normal thyroid. In conclusion, SOD seems to be related to cell proliferation and differentiation in the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor and hyperplastic follicular cells and because the Mn-SOD concentration is increased in papillary carcinoma or papillary-growing cells.

Humans

[Study of the localization and the concentration of superoxide dismutase in various thyroid disorders].

The localization of Cu/Zn and Mn superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals (O2-) to O2 and H2O2, in various thyroid disorders was studied by an immunohistochemical technique in 20% formalin fixed paraffin embedded thin sections using anti-human Cu/Zn and Mn-SOD antibodies. The concentrations of both SODs in those tissues were also measured by a sandwich enzyme immunoassay technique. Cu/Zn SOD was immunocytochemically stained in most of papillary carcinoma, and some of other disorders. In the normal follicular cells it localized in the perinuclear cytoplasm, whereas in the tumor or hyperplastic cells it was in the cytoplasm homogeneously. Mn SOD was strongly stained in papillary carcinoma and papillary growing cells in adenoma and Graves' disease. The concentrations of Cu/Zn and Mn SOD in every thyroid disorder were higher than those in normal thyroid, and it was much higher in the malignant tumors. The ratio of the concentration of Mn SOD against Cu/Zn SOD in the tissues was higher only in papillary carcinoma compared with that in normal thyroid. In conclusion, SOD seems to be relating to the cell proliferation and differentiation in the thyroid since both SODs increased in tumors and hyperplastic disorders, and Cu/Zn SOD changed its localization and Mn SOD existed predominantly in papillary carcinoma or papillary growing cells.

Carcinoma, Papillary

Deficient differentiation of mast cells in the skin of mi/mi mice. Usefulness of in situ hybridization for evaluation of mast cell phenotype.

The staining property of skin mast cells changed from Alcian blue+/berberine sulfate- to Alcian blue+/berberine sulfate+ in the skin of normal (+/+) and Wv/Wv mice. In contrast, this change did not occur in the skin of mi/mi mice. Heparin content and histamine content per a mi/mi skin mast cell were estimated to be 34% and 18% those of a +/+ skin mast cell, respectively. The low heparin content of mi/mi skin mast cells seemed to be consistent with the Alcian blue+/berberine sulfate- staining property. Expression of genes encoding mast cell-specific proteolytic enzymes was examined by Northern blotting and in situ hybridization. Messenger RNA of mast cell carboxypeptidase A was expressed most of all by +/+, Wv/Wv, and mi/mi skin mast cells, but mRNA of mouse mast cell protease (MMCP)-6 was expressed by approximately a half of +/+ and Wv/Wv skin mast cells and by only 3% of mi/mi skin mast cells. A significant amount of MMCP-2 mRNA was not expressed in the skin of all +/+, Wv/Wv and mi/mi mice. This shows the presence of at least three phenotypes in skin mast cells of mice: berberine sulfate+/MMCP-6+, berberine sulfate+/MMCP-6-, and berberine sulfate-/MMCP-6-. The in situ hybridization of mRNA of mast cell-specific proteolytic enzymes seemed to be useful to describe abnormalities of mast cell differentiation in the skin of mi/mi mice.

Animals

[Surgical stress induces the secretion of alpha human atrial natriuretic peptide].

The changes in plasma alpha-hANP level and the factors affecting its secretion were studied in 35 patients treated by surgery for gastrointestinal disease (laparotomy group, 17) and (non-laparotomy group, 18). They did not have any particular complication during the study period. alpha-hANP, catecholamine (CA), antidiuretic hormone (ADH), aldosterone and plasma renin activity (PRA) were determined serially before and after the surgery. Plasma alpha-hANP level elevated on the post-operative day 1 and dropped to the upper limit of the normal range by the day 3, then gradually recovered to the level of before surgery. This early elevation of alpha-hANP was more marked in the laparotomy group than in the non-laparotomy group. These change in alpha-hANP level correlated well to those of CA, but not to those of ADH, aldosterone, and PRA. Age, sex, duration of surgery, bleeding and infusion volume during surgery did not affect the difference in alpha-hANP secretion between the two groups. In conclusion, the early elevation of plasma alpha-hANP level was correlated well to the surgical stress, and that this alpha-hANP secretion might be induced by CA secretion.

Adult

Placental involvement by maternal non-Hodgkin's lymphoma.

We report a case of non-Hodgkin's lymphoma with placental metastasis. A 42-year-old pregnant women was diagnosed with non-Hodgkin's lymphoma at 26 weeks' gestation by needle-aspiration biopsy of the lung. She later delivered a boy at 28 weeks' gestation; however, despite resuscitation he died soon after birth. Histopathologically, we found malignant lymphoma cells invading the intervillous space of the placenta, but an autopsy on the neonate was not authorized. The patient died 10 months later of widespread malignant lymphoma, confirmed by autopsy. This case is interesting, since malignancy during pregnancy is rare, and even more infrequent are cases of maternal malignant lymphoma with placental metastasis.

Adult

[Treatment of advanced gastric and colorectal cancer with 5-FU, leucovorin and interferon-alpha].

Twenty-four patients with advanced or relapsed gastric or colorectal cancer were treated with a combination of 5-fluorouracil (5-FU), leucovorin (LV) and interferon-alpha (IFN-alpha). 5-FU was administered by rapid intravenous infusion at 350 mg/m2 for 5 consecutive days. Intravenous bolus administration of LV 20 mg/m2 was given before each 5-FU administration. This combination was repeated every 3 to 4 weeks. IFN-alpha (HLBI), 6MU, was administered subcutaneously daily. Of 13 patients with gastric cancer, there were 2 PR, 4 NC and 7 PD, and among 11 patients with colorectal cancer, there were 1 CR, 8 NC and 2 PD. All 16 previously treated patients had no clinical response. Responses were seen in patients with no prior chemotherapy and with good performance status. Most common toxicities observed were leucopenia, fever, stomatitis and diarrhea, which were all tolerable and reversible.

Adult

Malignant fibrous histiocytoma coexistent with mucinous cystadenoma of the pancreas.

A patient with malignant fibrous histiocytoma (MFH) coexistent with mucinous cystadenoma of the pancreas is reported. Primary MFH of the pancreas is rare, with only six patients reported in the world medical literature. A patient with MFH coexistent with a pancreatic mucinous epithelial tumor has not been reported previously, although two patients with pseudosarcomatous tumor associated with mucinous cystadenocarcinoma of the pancreas have been reported. Mural nodules of similar histologic appearance have been reported in ovarian mucinous tumors. The authors believe this to be the first report of the occurrence of MFH in mucinous cystadenoma of the pancreas.

Adult

c-kit Gene was not transcribed in cultured mast cells of mast cell-deficient Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding region.

The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice were not anemic, they showed a remarkable depletion of mast cells. Most homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ cells. However, male and female Wsh/Wsh mice have an appreciable number of germ cells in their gonads. We investigated the mechanism of specific depletion of mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c-kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant changes were found in the nucleotide sequence of the c-kit transcripts obtained from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c-kit gene expression in each cell type.

Anemia

Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in their defective responses to fibroblasts that express the ligand for c-kit.

Mutant mice of mi/mi genotype are osteopetrotic and deficient in tissue mast cells due to a defect in osteoclasts and mast cells. In an effort to further understand the mechanisms behind why mi/mi mouse-derived cultured mast cells (mi/mi-CMC) responded to interleukin-3 (IL-3), but not to the proliferative stimuli presented by fibroblasts, mi/mi-CMC and congenic normal (+/+) mouse-derived CMC (+/+-CMC), both of which expressed the phenotypic characteristics of immature mast cells, were cocultured with Swiss albino/3T3 fibroblasts in a medium containing IL-3. In the in vitro CMC/fibroblast coculture, mi/mi-CMC did not acquire the phenotypes of connective tissue-type mast cells (CTMC), while +/+-CMC did. In addition, attachment of mi/mi-CMC to the fibroblasts was found to be significantly lower than that of +/+-CMC. Because the interaction of c-kit product with its ligand (stem cell factor [SCF]) is known to play an important role not only in proliferation and differentiation of mast cells but also in attachment of CMC to fibroblasts, the expression and function of c-kit were investigated in mi/mi-CMC and +/+-CMC. Recombinant rat SCF (rrSCF164) induced a dose-dependent proliferation of +/+-CMC. Also, rrSCF164 induced +/+-CMC to acquire the phenotypes of CTMC in the medium containing IL-3. By contrast, rrSCF164 did not stimulate the proliferation of mi/mi-CMC nor induce a phenotypic change of the cells from immature mast cells to mature, CTMC-like mast cells. Immunoblotting with antiphosphotyrosine antibody showed that rrSCF164 induced considerable tyrosine phosphorylation of 145- to 165-Kd protein, the product of c-kit, in +/+-CMC, whereas tyrosine phosphorylation of the protein was barely detectable in mi/mi-CMC. Northern blot and flow cytometry analyses showed that mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+-CMC. Further, mi/mi-CMC were found to differ from +/+-CMC in the expression of mouse mast cell protease-6 (MMCP-6) and MMCP-2 messenger RNA transcripts. These results suggest that the gene product of the mi locus may be important in regulating the expression of gene products such as c-kit, and that mast cell deficiency of mi/mi mice appears to be due, at least in part, to impaired signaling through the c-kit receptor because of the low c-kit expression.

3T3 Cells

Infrequent mutation of the ras genes in skin tumors of xeroderma pigmentosum patients in Japan.

By using PCR amplification and oligonucleotide mismatch hybridization, base-substitution mutations of the ras genes in 26 skin tumors of Japanese xeroderma pigmentosum (XP) patients were studied. Thin sections of tumor tissues which were fixed and embedded in paraffin blocks were used in this study. After analyzing codons 12, 13 and 61 of the H-, K- and N-ras genes by using 66 oligomer probes, we detected only one mutation of the K-ras gene at codon 61 in one tumor sample. All the other tumors were therefore considered not to have a mutation in the ras genes. These results suggest that mutations of the ras genes are not particularly associated with skin tumors of Japanese XP patients.

Base Sequence

Distribution of histologic subtypes and sex ratio in various primary sites of lymphocytic lymphoma.

To examine the distribution of histologic subtypes and sex ratio in each primary site of lymphoma, 1,169 histologically proven cases of lymphocytic lymphoma were analyzed. The location of tumor was nodal in 615(53%) and extranodal in 517(44%), patients with the gastrointestinal tract being the most common. The incidence was predominantly in males for all histologic types and in nodal and extranodal sites, except for a predominance of females in extranodal lymphoplasmacytic(Lp-cytic), lymphoplasmacytoid(Lp-cytoid) tumors. Frequency of the Lp-cytic/Lp-cytoid type among all types of lymphoma in females was about 2.7 times more frequent in extranodal than in nodal sites. The most striking example was thyroid lymphoma in which the frequency of Lp-cytic/Lp-cytoid type was 36% in female and 0% in male patients. Including this type of lymphoma, frequency of low grade lymphoma in females was higher in extranodal sites than in nodal sites.

Adolescent

Cushing's syndrome induced by hypersecretion of cortisol from only one of bilateral adrenocortical tumors.

A case of Cushing's syndrome induced by the unilateral (right side) dominance of cortisol secretion in the face of bilateral adrenal tumors is reported. The adrenal tumor resected on the right side was a so-called black adenoma and histologically without any findings of nodular hyperplasia. After resection of the adrenal adenoma, no findings of cortisol hypersecretion from the remaining adrenal tumor on the left side were observed until the present, suggesting that the tumor of the left adrenal gland is a nonfunctioning adenoma. These data imply that the adrenal adenomas have primarily developed from the adrenal gland itself, rather than from micronodular hyperplasia by corticotropin stimulation, and that one of these tumors produces excess hormones initially by corticotropin stimulation, but the other remains in cell proliferation.

Adenoma

Composition and turnover of phospholipids and neutral lipids in human breast cancer and reference tissues.

The phospholipid (PL) content was 4-fold higher while the triacylglycerol (TG) content tended to be 65% lower in human breast cancer tissues as compared with non-cancerous reference parts from excised breast tissues. The variation in TG content among breast tissues was very large while that of PL was relatively small. The fatty acid compositions of PL were significantly different between the cancer and reference tissues; the proportions of octadecenoate (18:1), docosahexaenoate (22:6n-3), the total n-3 fatty acids and the n-3/n-6 ratio, but not the proportion of arachidonate (20:4n-6), were significantly higher in the major PL of cancer tissues as compared with those of the reference tissues. No significant differences were observed in the proportion of the major fatty acids of TG in these tissues. The turnover of lipids was faster in the cancer tissues than in the reference tissues. The turnover of TG was faster than that of PL in the cancer tissues, whereas the opposite was true in the reference tissues, indicating significant differences in lipid metabolism between these tissues. A striking difference in the n-3 and n-6 fatty acids of the reference tissues noted for Japanese and Finnish women is discussed in relation to the roles of eicosanoids and eicosanoid precursors in mammary carcinogenesis.

Adult

Rhabdomyosarcoma coexistent with ovarian mucinous cystadenocarcinoma: a case report.

This report describes a case of ovarian mucinous cystadenocarcinoma associated with rhabdomyosarcoma. Several cases of sarcoma-like mural nodules in ovarian mucinous tumor have been described previously, but only three well-documented cases of true sarcoma have been reported. The first case was a fibrosarcoma associated with a mucinous cystadenoma; the second was an undifferentiated sarcoma in a mucinous cystadenocarcinoma; and the third was a fibrosarcoma occurring in a mucinous cystadenocarcinoma. The occurrence of rhabdomyosarcoma in mucinous cystadenocarcinoma, as reported here, is to our knowledge the first case reported of this unusual combination of tumors.

Cystadenocarcinoma

Bilateral primary non-Hodgkin's lymphoma of the adrenal glands with adrenal insufficiency: a case report.

A 72-year-old woman with bilateral non-Hodgkin's lymphoma of the adrenal glands causing adrenal insufficiency is reported. The left-side lymphoma (diffuse large B-cell lymphoma) was removed surgically but the right-side lymphoma could not be removed. Complete response was obtained with subsequent combined chemotherapy and was maintained for 6 months with repeated chemotherapies. However, the patient died of liver recurrence 1 year after admission. In cases of malignant lymphoma forming a bulky mass, surgery with subsequent chemotherapy appears to reduce the cancer volume and improve the therapeutic outcome.

Adrenal Gland Neoplasms

Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene.

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.

Alleles

Immunodetection of sialyl-Tn antigen in normal, hyperplastic and cancerous tissues of the uterine endometrium.

The expression of sialyl-Tn antigen (STn) in normal, hyperplastic and neoplastic tissues of the uterine endometrium was examined by immunoperoxidase staining of formalin-fixed, paraffin-embedded samples using the monoclonal antibody TKH-2, directed toward the STn structure (NeuAc 2-6GalNac 1-O-serine or threonine). STn was expressed in 13 of 18 normal postovulatory endometria with an increasing staining intensity and incidence in the late secretory phase. It was consistently absent in 10 proliferative endometria. None of 5 cystic, 4 adenomatous or 12 atypical hyperplasias expressed STn, but areas of severe cytological atypia in 3 atypical hyperplasias showed faint expression. STn expression was detected in 36 of 43 adenocarcinomas. Although the extent of staining varied from a few to most of the cancer cells, general staining was observed throughout the cytoplasm of cancer cells with increased staining of the luminal surface and frequent positive staining of intraluminal mucin. Thus, it is clear that STn is selectively expressed in cancer cells and shows restricted expression in normal and hyperplastic endometrial tissues. STn may be an early marker of malignant transformation and has potential for use as a diagnostic aid in the surgical pathology of the uterine endometrium.

Adenocarcinoma