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Biomedical subjects

Y Tsuchiya

Publications and source records attributed to Y Tsuchiya.

At least 127 records · Page 7Linked to original sources

Japanese type of spondylo-metaphyseal dysplasia.

Five members of a Japanese family with a new form of spondylo-metaphyseal dysplasia (SMD) are reported. Another member was also probably affected. The disease was characterised by severe coxa vara, moderately severe metaphyseal changes of the long bones of the lower limbs, mild changes in the long bones of the upper limbs and grossly normal short tubular bones. Platyspondyly, present in the boys, was less marked in their father, whereas two affected aunts had normally shaped vertebral bodies.

Adult↗

Isolation of genes differentially expressed between the Yoshida sarcoma and long-survival Yoshida sarcoma variants: origin of Yoshida sarcoma revisited.

The Yoshida sarcoma (YS) is characterized by growth as "free cells" in ascites. Long-survival Yoshida sarcoma (LY) variants, which develop after transplantation of YS into immunologically conditioned Donryu rats, in contrast, form "islands" in ascites. A representational difference analysis (RDA) approach was adopted to isolate genes differentially expressed between YS and LY variants to elucidate the molecular mechanism of their development. Fifteen clones presenting differences in expression were characterized. Nine genes (those encoding for the high-affinity IgE receptor gamma chain, pJG116 repetitive sequence, non neuronal enolase, proteasome subunit RC1, cytotoxic T lymphocyte-associated gene transcript CTLA-1, interleukin-2 receptor gamma chain, and three unknown sequences) expressed mRNA in YS, but showed lower or no expression of mRNA in LYs. The mRNAs of the other six genes (those encoding for cytokeratin 8, cytokeratin18 (Endo B), TIMP2 and three unknown sequences) were not found in YS, but were present in LYs. Interestingly, CTLA-1 is a non-epithelial (hematopoietic) cell-specific gene in terms of transcription, while cytokeratin 8 and cytokeratin 18 are both epithelium-specific genes. Immunohistochemically, YS expressed T-cell specific antigens CD2 and CD3, and T cell receptor beta and gamma chain genes were rearranged in YS, but not in LYs. Moreover, using restriction fragment length polymorphism probes, we found that LYs exhibited different cell lineage from YS. Thus, our present findings, unexpectedly, raise fundamental questions concerning the cellular origins of YS and LY variants rather than pointing to any specific mechanism to explain the LY phenomenon.

Animals↗

[A study on stressful life events of workers in Japan].

The experience rates of eighteen life events of Japanese workers were surveyed and the strength of each of the events was evaluated by a self-reported questionnaire. The fifteen professions surveyed included construction, transport, mailing, chemical production, banking, newspaper, TV services, commercial publishing, advertising, teaching and civil service. The number of workers who answered was 18,657 males and 4,443 females, aged 20 to 59 years. The male workers were divided and analysed in six job groups: clerical workers (n = 5,866), professionals (n = 3,696), blue collar day workers (n = 1,623), blue collar night or shift workers (n = 3,191), drivers (n = 1,663) and construction workers (n = 2,466). They were divided into groups and compared according to job, sex and five different age groups. The highest experience rate in each of the life events such as family trouble for both sexes, death of a family member, financial trouble and anxiety, death of a close friend, dissatisfactory transport to workplace or job, respectively. Comparing the experience rates between males and females we found no significant difference for five items. However, other items had higher experience rates for males than for females with the exception of family trouble. In regard to the age characteristics of each of the life events, as the age increased the experience rates of health-related life events such as the death of a spouse, child, family member or close friend and one's own illness or injury became higher. In contrast, the experience rates of items such as moving to a worse residence and failure in a school or training program became lower as the age increased for both sexes. Among job groups, construction workers had the highest experience rates of most life events except for the item of dissatisfactory transport to the workplace or job. Among other job groups, drivers had higher experience rates in the following four items: re-employment, death of spouse, divorce and financial trouble and anxiety. Blue collar day workers had higher rates for failure in school or training program and family trouble. The blue collar night or shift workers had higher rates for failure in school or training program and dissatisfactory transport to the workplace or job. The mean values of strength in six life events: re-employment, death of a family member, death of a close friend, serious physical illness, dissatisfactory transport to the workplace or job and family trouble were stronger in females than in males.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Incomplete androgen insensitivity associated with a thermolabile androgen receptor.

One infant and a cousin with incomplete androgen insensitivity syndrome were reported. The familial pedigree showed that the disorder was inherited in three generations in X-linked recessive fashion. An androgen binding study of cultured genital skin fibroblast from patients showed normal maximum binding capacity and a normal apparent dissociation constant. Heat stability assay showed binding decreased to less than 30% at 41 degrees C compared with the amount at 30 degrees C, indicating that the androgen receptor was thermolabile.

Androgen-Insensitivity Syndrome↗

Hypopituitarism with invisible pituitary stalk: two case reports of males with micropenis suggesting fetal onset of hypopituitarism.

The presence of hypopituitarism and invisible pituitary stalk on a magnetic resonance image (MRI) is commonly attributed to birth trauma. Two patients with severe hypopituitarism and invisible pituitary stalk are presented. One was born by breech delivery, the other by Cesarean section. The presence of a micropenis since early infancy in these two patients suggested that their hypopituitarism might have begun during early fetal life thus effecting penile growth during the second and third triministers of gestation. These findings raise the possibility that the association of hypopituitarism and invisible pituitary stalk may have multiple etiologies including hormonal abnormalities during early fetal life.

Adolescent↗

The crystalline structure of pancreatic calculi.

The present study was carried out to investigate the ultrastructure and composition of crystals of pancreatic calculi. Microradiography showed that they were irregularly mineralized with radial or stratified zones of low mineralization. The crystals were identified as calcite composed of CaCO3 in X-ray and electron diffraction studies. Scanning electron microscopy (SEM) revealed that the calculi consist of aggregations of rhombohedral, fang-shaped, botryoidal, foliaceous, and plate-shaped crystals. Some of them showed signs of partial dissolution on their surface. Transmission electron microscopy (TEM) showed crystals of various sizes and shapes either solitary or in clumps. The direct measurement of crystalline lattice intervals obtained from each crystal was 0.386 nm in accordance with the diffraction data. Exocrine pancreatic cell debris are present in pancreatic calculus matrices.

Calculi↗

Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo.

Tissue inhibitors of metalloproteinases (TIMPs) are the negative regulators of matrix metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are believed to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12-O-tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system.

Animals↗

Pharmacokinetics of (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt and (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu administered intravenously to beagle dogs.

The pharmacokinetics of two analogues (NT-1 and NT-2) of the smallest active fragment of neurotensin were investigated in beagle dogs after intravenous (iv) administration at the doses of 0.1 and 0.5 mg/kg for NT-1 and of 0.25 and 0.5 mg/kg for NT-2. After iv administration of these two drugs, the plasma levels decreased with time with a biexponential pattern, and linear kinetic behavior was observed. The pharmacokinetic parameters (mean +/- standard error of mean) after iv administration of NT-1 at 0.1 mg/kg were as follows: the half-life of the distribution phase (t1/2 alpha) was 0.29 +/- 0.11 h, the half-life of the terminal phase (t1/2 beta) was 1.99 +/- 0.41 h, total plasma clearance (CL) was 33.2 +/- 6.3 mL/h/kg, steady-state volume of distribution (Vdss) was 57.1 +/- 2.8 mL/kg, and mean residence time (MRT) was 2.20 +/- 0.55 h. The t1/2 alpha, t1/2 beta, CL, Vdss, and MRT values after iv administration of NT-2 at 0.25 mg/kg were 0.11 +/- 0.02 h, 0.58 +/- 0.04 h, 257.3 +/- 17.2 mL/h/kg, 180.3 +/- 4.6 mL/kg, and 0.71 +/- 0.04 h, respectively. After iv administration of NT-1, NT-2 was detected in the plasma. It was confirmed from this result that NT-1 was metabolically hydrolyzed to NT-2 in the body of beagle dog.

Amino Acid Sequence↗

Unmasking of latent hypoparathyroidism in a child with partial DiGeorge syndrome by ethylenediaminetetraacetic acid infusion.

DiGeorge syndrome is a rare congenital anomaly with a wide range of clinical manifestations. This syndrome is usually associated with hypocalcaemia resulting from primary hypoparathyroidism. We report here a case of an 8-year-old boy with partial DiGeorge syndrome who presented initially with neonatal hypocalcaemia, but was subsequently normocalcaemic. Latent hypoparathyroidism was unmasked by a diagnostic EDTA infusion resulting in hypocalcaemia without a parathyroid hormone response. We propose that EDTA infusions can be useful in the diagnosis of latent hypoparathyroidism in children.

Child↗

Acceleration of natural killer (NK) cell recovery by a glucan, sizofiran, in anti-asialoGM1 antibody-treated mice.

The proportion of asialoGM1 positive cells and NK activity of murine splenic cells was reduced to almost zero one day after intravenous injection of rabbit anti-asialoGM1 antibody. The cells and the activity started to increase at the latest 3 days after the injection, although the proportion was far below that of the normal control. The proportion of asialoGM1 positive cells and NK activity increased more remarkably when 1,3-beta glucan, sizofiran, was administered intramuscularly one day after the antibody injection. The increases were dose related (50-1000 micrograms/mouse). The fact that sizofiran hastened the recoveries of splenic NK activity and asialoGM1 positive cells suggests sizofiran may have the activity to accelerate the differentiation of asialoGM1 positive NK cells.

Animals↗

Nonspecific crossreacting antigen (NCA) is a major member of the carcinoembryonic antigen (CEA)-related gene family expressed in lung cancer.

Carcinoembryonic antigen (CEA) is one of the most important tumour markers in the management of human carcinoma, including lung cancer. So far, however, because of the nonspecificity of anti-CEA antibodies, it remains unclear whether the experimental measurements of CEA expression really reflect genuine CEA. In normal lung, nonspecific cross reacting antigen (NCA) has been described as a major component of CEA-related antigens. Recently isolated CEA and NCA cDNA clones enabled us to analyse CEA and NCA expression of in vivo tumour specimens and tumour cell lines at mRNA levels. NCA-specific mRNA (but not CEA-specific mRNA) was detected in all normal lung tissues examined. Of 21 lung cancer tissue specimens, nine expressed both NCA and CEA and five expressed only NCA. Of 16 tumour cell lines, two expressed only NCA and one expressed both NCA and CEA, although its level of CEA mRNA was weaker than that of NCA mRNA. Therefore, CEA-related mRNA expression was always accompanied by NCA mRNA expression; there were no cases of CEA mRNA expression alone. These findings suggest that NCA is a major member of the CEA-related gene family expressed in lung cancer.

Animals↗

Inhibitory effects of sizofiran on anticancer agent- or X-ray-induced sister chromatid exchanges and mitotic block in murine bone marrow cells.

The inhibitory effects of a biological response modifier (BRM), sizofiran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various anticancer agents or irradiation were investigated. Sizofiran (10 mg/kg i.m.) inhibited SCEs induced by mitomycin C (2 mg/kg i.v.), adriamycin (20 mg/kg i.v.) and cyclophosphamide (20 mg/kg i.v.) by about 20%, respectively. Analysis of the SCEs in vivo after irradiation plus sizofiran indicated that SCE levels were significantly lower than those observed in mice exposed to irradiation without sizofiran. Moreover, the effects of sizofiran were dependent on the timing of administration. Our results indicated that sizofiran should be administered simultaneously or soon after irradiation in order to minimize damage. Sizofiran also markedly restored the bone marrow cell mitosis which had been suppressed by anticancer agents, and this action was closely correlated with the prevention of increase in SCEs. These results indicate that in addition to immunopotentiating activity, sizofiran may play a role in preventing chromosomal damage induced by cancer chemotherapy and radiotherapy.

Animals↗

Bone marrow transplantation for late infantile metachromatic leukodystrophy: pathogenic investigation for graft rejection.

A Japanese boy aged 2 years 11 months with late infantile metachromatic leukodystrophy underwent bone marrow transplantation (BMT) from his human leukocyte antigen (HLA) identical but mixed lymphocyte culture reactive father. Chimerism and increased arylsulfatase A activities of leukocytes had been observed with retarded progression of neurological deterioration during the first 3 months post-BMT. Graft rejection gradually occurred and donor cells were almost completely eliminated from the patient at 1 year after BMT. The process of neurodegeneration progressed clinically and neuroradiologically. Three possible reasons for the pathogenesis of graft rejection are: (i) T cell depletion of donor marrow cells as graft-versus-host disease (GVHD) prophylaxis; (ii) a slightly weak conditioning regimen: and (iii) a small number of marrow cells transplanted. It is stressed that as BMT is still a preliminary therapy for metachromatic leukodystrophy indications, conditioning, and GVHD prophylaxis for BMT should be considered individually.

Bone Marrow Transplantation↗

Enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae.

Squalene epoxidase is a microsomal membrane-associated enzyme that acts as an important regulator in the sterol biosynthetic pathway. In this study, the enzymatic properties of squalene epoxidase from Saccharomyces cerevisiae were examined. Unlike Candida squalene epoxidase, S. cerevisiae squalene epoxidase required NADPH for enzyme reaction. However, S. cerevisiae enzyme reaction did not require FAD or autologous S105 fraction. Unlike rat squalene epoxidase, the activity of S. cerevisiae was reduced by Triton X-100, a nonionic detergent. Terbinafine, an inhibitor of fungal squalene epoxidase, inhibited the enzyme in a non-competitive manner, while NB-598, an inhibitor of mammalian squalene epoxidase, barely inhibited it in a partially non-competitive manner. Thus, the properties of squalene epoxidase from S. cerevisiae were different from those of squalene epoxidase from rats and Candida, which were previously known. We propose that a species difference of squalene epoxidase exists not only between animals and fungi but between Candida and Saccharomyces.

Animals↗

Pharmacokinetics of novel hexapeptides with neurotensin activity in rats.

A high-performance liquid chromatographic method to determine (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu (NT-2) with neurotensin (NT) activity in rat plasma was developed and a pharmacokinetic study was performed in rats. Quantitative analysis with high reproducibility was achieved for NT-2 over the concentration range of 1.14-500 ng/ml. (Me)Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt (NT-1) was rapidly hydrolyzed to NT-2 in rat plasma at 37 degrees C. This degradation of NT-1 was observed as a pseudo first-order reaction, and the pseudo first-order rate constant was calculated to be 7.26 min-1 (t1/2 = 0.095 min). The pharmacokinetic profiles of NT-2 after intravenous administration of NT-1 at doses of 0.1 and 0.3 mg/kg were compatible with that of NT-2 after intravenous administration of NT-2 at 0.5 mg/kg. Range of the half-life of the terminal phase (t1/2 beta) of NT-2 was 0.36-0.53 h. The absolute bioavailabilities after oral administrations of NT-1 and NT-2 at a dose of 20 mg/kg were 0.61 +/- 0.17 (mean +/- S.E.) and 0.19 +/- 0.08%, respectively. It was found that NT-1 was more suitable for oral administration than NT-2.

Administration, Oral↗