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Biomedical subjects

T Sakiyama

Publications and source records attributed to T Sakiyama.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Purine nucleoside phosphorylase (PNP) deficiency].

The clinical manifestation, diagnosis, pathogenesis, pathophysiology and treatment of purine nucleoside phosphorylase (PNP) deficiency is overviewed. Among the severe combined immunodeficiency syndrome (SCID), PNP deficiency was 2ndly found as an autosomal recessively heritable purine metabolic disease. This disease is characterized by severe T-cell immunodysfunction accompanied by marked low level of uricemia and uricosuria. In addition, this concurrence strongly suggests the diagnosis of PNP deficiency. Neurological manifestations are found in two-third of the reported cases. About 30 cases have been reported worldwide. Their ages at onset varied from birth to 6 years and their outcome is usually fatal terminating in viral infection or lymphoma. Our first case and her sister died with varicella and lymphoma, respectively. No clinical benefit was found with normalized uricemia after erythrocyte transfusion in our case. Bone marrow transplantation and future gene therapy are reviewed.

Bone Marrow Transplantation↗
PubMed1995

Expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on sugar chains of glycoproteins including carcinoembryonic antigens in human colon adenocarcinoma: applications of Trichosanthes japonica agglutinin I for early diagnosis.

The N-linked sugar chain structures of the carcinoembryonic antigen (CEA) produced by liver metastases of colon cancers and the normal counterpart of CEA purified from human adult feces (NFA-2) were previously determined comparatively (K. Fukushima, T. Ohkura, M. Kanai, M. Kuroki, Y. Matsuoka, A. Kobata, and K. Yamashita. Glycobiology, 5:105-115, 1995). Seventy-five % of NFA-2 contained complex type sugar chains with Gal beta 1-->3GlcNAc residues, in contrast to the sugar chains of CEA, in which over 90% of the oligosaccharides contained Gal beta 1-->4GlcNAc residues, and Sia alpha 2-->6Gal beta 1-->4GlcNAc residues were detected in 18 to 65% of the oligosaccharides. The expression of Sia alpha 2-->6Gal beta 1-->4GlcNAc residues on CEA molecules in sera and tissues was investigated using Trichosanthes japonica agglutinin I (TJA-I), which interacts with Sia alpha 2-->6Gal beta 1-->4 GlcNAc residues. Ten purified CEA samples bound to a TJA-I column while seven NFA-2 samples passed through the column. Various concentrations of serum CEA samples from patients with metastatic colon cancers exclusively bound to the TJA-I column, reflecting that CEA molecules exfoliated into the blood circulation comprise sugar chains with Sia alpha 2-->6Gal beta 1-->4GlcNAc residues. In histochemical studies involving biotinylated TJA-I, normal mucosa (n = 20) and benign adenomas (n = 20) were not stained, and 83% of well and moderately differentiated colon adenocarcinomas (n = 53) reacted with TJA-I, although poorly differentiated ones (n = 9) and mucinous specimens (n = 10) were negative. Because over 90% of colon adenocarcinomas can be differentiated, TJA-I staining might be applicable to the early diagnosis of colon cancers.

Adenocarcinoma↗
PubMed1995

[Mini review: animal model of human lysosomal storage disease].

A number of true genetic animal model of human inborn errors of metabolism, caused by a specific enzyme defect are known. Recently, in addition to the naturally occurring diseases of animals, genetic engineering techniques such as transgenic or gene targetting, provide the animal models with specific gene defect. Such animal systems with lysosomal enzyme defect are summarized herein. Several animal model systems with lysosomal enzyme defect have been used to study the therapeutic strategies such as bone marrow transplantation and/or gene therapy. In this review, mucopolysaccharidosis VII mice treated with bone marrow transplantation and gene therapy, mucopolysaccharidosis VI rats and Niemann-Pick type C mice treated with bone marrow transplantation are mainly introduced. The latter two animals were established in Japan.

Animals↗
PubMed1994

[Osteoporosis in congenital disorders].

Osteogenesis imperfecta (OI) is the most prevalent osteoporosis syndrome in childhood and is characterized by fractures and skeletal deformities. In almost all individuals, OI results from mutations in one of the two genes (COL1A1 and COL1A2) that encode the chains of type I collagen. OI can be divided into four major groups, type I, II, III, and IV, that differ in clinical presentation, mode of inheritance, radiographic picture, and, for the most part, the biochemical basis of the connective disorder. The molecular basis of OI is mainly discussed.

Collagen↗
PubMed1993

Prenatal monitoring of ornithine transcarbamoylase deficiency in two families by DNA analysis.

We examined the DNA in two families with ornithine transcarbamoylase (OTC) deficiency. Two point mutations of the OTC gene, a C-to-T (codon 141) and a G-to-A (codon 141), were identified. This allowed prenatal monitoring to be made for two fetuses in each family, using polymerase chain reaction (PCR), followed by allele-specific oligonucleotide hybridization or TaqI digestion of amplified sequence. The diagnoses showed heterozygotes of a wild type gene and the corresponding mutant gene in these fetuses; each was confirmed postnatally.

Amino Acid Sequence↗
PubMed1992

The primary structure of mouse saposin.

The primary structure of mouse sphingolipid activator protein (saposin) was determined by cDNA sequencing. The amino acid sequence predicted by the cDNA sequence revealed that mouse saposin was highly homologous to human saposin and also to rat sertoli cell glycoprotein. Mouse saposin also has four functional domains, which are structurally similar to each other, and each domain has cysteines, prolines, and a potential glycosylation site at an almost identical position. An amino acid comparison between human and mouse saposins revealed that the similarity was approximately 70%, and human saposin lacks thirty-one amino acids between domains C and D. Heterogeneities of mRNA were found in both the coding and noncoding regions.

Amino Acid Sequence↗
PubMed1992

A cell line derived from sphingomyelinosis mouse shows alterations in intracellular cholesterol metabolism similar to those in type C Niemann-Pick disease.

Cell lines derived from the sphingomyelinosis (gene symbol, spm) mouse were established from homozygous (spm/spm) and heterozygous (spm/+) embryos according to a rigid 3T3 transfer schedule. The SPM-3T3 cells derived from a homozygous embryo showed extensive accumulation of intracellular cholesterol, attenuated esterification of exogenously added cholesterol and increased de novo cholesterol synthesis, when compared to SPMH-3T3 cells derived from a heterozygous embryo. The phenotypic abnormalities were very similar to those observed in fibroblasts from patients with Niemann-Pick disease type C (NP-C), in which a defect in the intracellular transport of unesterified cholesterol is suggested. The genetic defect in SPM-3T3 cells should be closely related to that in NP-C. The SPM-3T3 cell line is useful for biochemical and genetic studies on the regulation of intracellular cholesterol metabolism.

3T3 Cells↗
PubMed1991

Retrospective survey of urea cycle disorders: Part 2. Neurological outcome in forty-nine Japanese patients with urea cycle enzymopathies.

We analyzed neurological data, including DQ or IQ, EEG, and CT scan, in 49 patients with urea cycle enzymopathies, all of whom were included in a retrospective survey from 1978-1988 in Japan. We classified 3 groups depending on age-at-onset: group 1 (0-28 days, N = 11), group 2 (29 days-5 years, N = 31), and group 3 (greater than 5 years, N = 7). The least DQ or IQ score and the highest CT score, representing the most severe brain damage was found in group 1, and the highest DQ or IQ and the least CT score was found in group 3. Intermediate scores of both parameters were found in group 2. There was a negative correlation between these 2 parameters (r = -0.82, P less than 0.01). Abnormal EEG during the attack-free period was predominantly observed in patients with CT abnormalities compared to those with a normal CT scan (P less than 0.01). Approximately 40% of the patients, mostly in groups 2 and 3 (92.8%) had normal findings in all 3 parameters. Thus, the magnitude of developmental abnormalities is clearly related to the degree of brain damage and to the age-at-onset of these diseases.

Brain↗
PubMed1991

Altered protein tyrosine kinase levels in human colon carcinoma.

To further understand the molecular mechanisms and the biological indicators of colonic tumorigenesis, the authors examined tyrosine kinase activity in the cytosol and in the particulate fraction of the homogenates of specimens from 20 human colonic carcinomas and compared them with the adjacent normal mucosal tissues. Total protein tyrosine kinase activity could be precisely detected using miniphosphocellulose column purification and a synthetic peptide, Glu-asparagine (Asp)-alanine (Ala)-Glu-tyrosine (Tyr)-Ala-Ala-arginine (Arg)-Arg-Arg-glycine (Gly) (E11-G1), as an artificial substrate. Tyrosine kinase activity of colonic carcinoma and normal mucosa was reduced in the cytosol fraction whereas activity in the particulate fraction was elevated with respect to protein concentration. The average specific activity ratios were 1.95 +/- 0.27 (normal cytosolic/carcinoma cytosolic) and 0.57 +/- 0.01 (normal particulate/carcinoma particulate) for tyrosine kinase activity. Cellular distribution (% cytosol) of tyrosine kinase activity in normal mucosa and in carcinoma varied from 21.0% to 91.2% and from 7.0% to 61.4%, respectively. In nearly all cases the percentage of cytosolic tyrosine kinase activity in carcinoma tissues was lower than in normal tissues. There was no difference due to histologic type or the presence of adenomatous components. A significant decrease of cytosolic tyrosine kinases was correlated with Dukes' Stage A. With advancing Dukes' stage, the average specific activity ratios (normal cytosol/carcinoma cytosol) were decreased. This study indicates that colonic carcinogenesis might be associated with alterations in cellular levels of tyrosine kinase activity and that the average specific activity ratio (normal cytosol/carcinoma cytosol) had a possible correlation with colonic tumor growth.

Colonic Neoplasms↗
PubMed1991

Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.

In a retrospective survey done from 1978-1988 in Japan, 32 male patients with ornithine transcarbamylase (OTC) deficiency were identified. We classified a neonatal and 2 late-onset groups, depending on clinical manifestations and the age at onset; group 1 (0-28 days; N = 10), group 2 (29 days-5 years; N = 13), and group 3 (greater than 5 years; N = 9). Compared to findings in the group 2 patients, there was a higher rate of mortality and a higher incidence of mental retardation in association with a great decrease in enzyme activity in group 1. In group 3, the mortality rate and enzyme activities were similar to those in group 1. However, patients in this group were asymptomatic prior to the first episode. Enzyme activities were measured mostly in autopsy samples. The serum citrulline levels (enzyme product) were highest in this group. Thus, the mutant enzymes were apparently labile with greater activities in vivo than in vitro. Treatments, including a protein-restricted diet, arginine supplementation, and sodium benzoate administration, resulted in a favorable prognosis for survivors with partial enzyme deficiency. We wish to emphasize that the incidence of late onset of this disease is higher than heretofore considered.

Child, Preschool↗
PubMed1991

Hemodynamics in the prone jackknife position during surgery.

We examined the hemodynamic changes occurring with prone jackknife positioning during colorectal surgery. The operative procedure was restorative proctocolectomy with ileal J-pouch anal anastomosis in five patients with adenomatosis coli and six patients with ulcerative colitis and anoabdominal resection of the rectum with colonic J-pouch anal anastomosis in eight patients with rectal cancer. Nineteen patients (10 men and 9 women aged 41 +/- 19 years) were monitored with arterial and Swan-Ganz catheters during positioning. Measurements were obtained in the supine and prone positions (1 minute, 3 minutes), and the jackknife position (1, 3, 5, and 10 minutes), as well as before and after adoption of the Lloyd-Davies position (1, 3, 5, and 10 minutes). Turning the patient from the supine position to the prone position resulted in a significant decrease in the cardiac index (CI). However, following head-down rotation, the CI increased and returned to the value seen in the supine position (p less than 0.05). Heart rate (HR) slowed and mean arterial pressure (MAP) increased in the prone jackknife position. We concluded that the extent of the changes in cardiac function presented no serious problems.

Adenoma↗