Search PubMed⌕ Search

Biomedical subjects

S Tsuchiya

Publications and source records attributed to S Tsuchiya.

At least 181 records · Page 10Linked to original sources
PubMed1994

Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency.

The IL-2R gamma-chain is an indispensable subunit for the functional IL-2R. Recently, mutations of the gamma-chain have been reported to be closely associated with X-linked severe combined immunodeficiency (XSCID). The present study reveals that three patients with XSCID have three different mutations in the gamma-chain; a point mutation, a two consecutive-base deletion, and lack of the second exon in mRNA. The point mutation that we have detected is C to T, which results in one amino acid substitution of valine for alanine in the extracellular domain of the IL-2R gamma-chain (named AV mutant). The two-base deletion detected causes a frame shift of the coding region in the SH2 subdomain in the cytoplasmic domain (named tSH mutant). Transfection studies performed with the mutant gamma-chains demonstrated that the AV mutant and tSH mutant failed to bind to IL-2 and to transduce growth signals, respectively. These findings indicate that the gamma-chain gene mutations that accompany XSCID induce loss of the gamma-chain function, possibly resulting in stagnation of the differentiation and development of T cells.

Base Sequence↗
PubMed1994

Apolipoprotein E5 and E7 in apparently healthy Japanese males: frequencies and relation to plasma lipid levels.

In order to determine the frequencies of apolipoproteins (apo) E5 and E7 and their relation to plasma lipid levels, apo E phenotypes were determined in 608 healthy Japanese male adults by two-dimensional gel electrophoresis. Apo E5 and E7 were observed in 2.8% of the subjects, in addition to the three common apo E isoforms, E2, E3, and E4. Apo E5 was divided into two subtypes based on the migration rate on SDS/PAGE, E5f is the type with faster migration and E5s slower migration. The gene frequencies were: the epsilon 3 allele, 0.841; the epsilon 4 allele, 0.095; the epsilon 2 allele, 0.049; the epsilon 7 allele, 0.009; the epsilon 5 allele encoding apo E5f (the epsilon 5f allele), 0.004; and the epsilon 5 allele encoding apo E5s (the epsilon 5s allele), 0.001. The five individuals with apo E5f and the eleven with apo E7 were heterozygotes and normocholesterolemic. Also plasma apo B and apo E levels were not increased in any subjects with apo E5f or apo E7. The data suggests that apo E5f and E7 are not rare in the Japanese population but that neither apo E5f nor E7 are associated with hypercholesterolemia in most of the heterozygotes.

Adult↗
PubMed1994

Induction of oral tolerance after feeding of ragweed pollen extract in mice.

The induction of oral tolerance following the feeding of ragweed pollen and its extract was investigated in BALB/c mice. Antibody class-specific immune suppression could be observed, and the IgE response was specifically suppressed, depending on the amount of ragweed pollen extract fed when subsequently immunized with ragweed extract together with A1(OH)3 as an adjuvant. A multiple feeding was more effective than a single feeding of antigen, and the IgE response was completely suppressed when 20 mg of pollen extract was fed for 5 consecutive days. On the other hand, IgG production was not suppressed even though a large amount of ragweed pollen or its extract was fed. Furthermore, no secretion of antigen-specific IgA into saliva was observed in control animals or those fed ragweed pollen extract. Thus, pollen extract feeding may be potentially useful for the prophylaxis or therapy of allergic rhinitis induced by ragweed.

Administration, Oral↗
PubMed1994

Activation of systemic and mucosal immune response following nasal administration of liposomes.

Adjuvant effects of liposomes on systemic and mucosal immune response were investigated following nasal administration to Balb/c mice. Bovine serum albumin (BSA)-specific serum IgG and salivary IgA levels were significantly elevated when BSA-associated liposomes were administered intranasally twice at 4-week intervals. Systemic immune response was activated only by negatively charged liposomes, while activation of mucosal immune response was independent of liposomal charge. Antigen localization in liposomes affected immune adjuvant effect; the mucosal immune response could be activated only by liposomes to whose surface BSA was attached, but the systemic immune response was activated by both liposomes to which antigens were attached and in which the encapsulating antigens occurred. The results suggest that the contribution of antigen-presenting cells in activation of systemic and mucosal immunity following intranasal administration is different.

Adjuvants, Immunologic↗
PubMed1994

Activation of Fc receptor-mediated phagocytosis by mouse peritoneal macrophages following the intraperitoneal administration of liposomes.

The effects of liposomes on the phagocytic activity of mouse peritoneal macrophages were investigated using IgG-opsonized sheep red blood cells (SRBC). The highest ingestion index of opsonized SRBC via Fc receptors of macrophages from BALB/c mice was observed for macrophages harvested on day 4 following the intraperitoneal injection of liposomes (2.27 mumol lipid/mouse). An increase in the ingestion index was observed irrespective of liposomal charge. Binding parameters of Fc receptors of macrophages from liposome- or saline-injected mice were determined using horseradish peroxidase-conjugated IgG, and an increase in the number of binding sites with the same binding constant was observed in macrophages from liposome-injected mice. The activation mechanism of mouse peritoneal macrophages by liposomes differed from that by lipopolysaccharides. Liposomes thus appear to contribute to the activation of immune response.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Structure of the N-terminal SH3 domain of GRB2 complexed with a peptide from the guanine nucleotide releasing factor Sos.

Src-homology 3 (SH3) domains mediate signal transduction by binding to proline-rich motifs in target proteins. We have determined the high-resolution NMR structure of the complex between the amino-terminal SH3 domain of GRB2 and a ten amino acid peptide derived from the guanine nucleotide releasing factor Sos. The NMR data show that the peptide adopts the conformation of a left-handed polyproline type II helix and interacts with three major sites on the SH3 domain. The orientation of the bound peptide is opposite to that of proline-rich peptides bound to the SH3 domains of Abl, Fyn and p85.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Plasminogen with type-I mutation in the Chinese Han population.

A functionally inactive plasminogen (PLG) variant, PLG M5, is polymorphic in the Japanese population and has a codon 601 mis-sense mutation (GCT for Ala to ACT for Thr), designated type-I mutation. The present study aimed to reveal whether the plasminogen with type-I mutation is present in the Chinese Han population. Among 104 healthy Chinese students, phenotype PLG AM5 was found in three subjects (2.9%), while 100 subjects were phenotype A and one was phenotype AA3. In the three subjects with PLG AM5, plasma concentrations of immunoreactive PLG were normal but PLG activities were decreased. Analysis using PCR and dot-blot hybridization with allele-specific oligonucleotide probes revealed the presence of the type-I mutation in the PLG gene of all three subjects with PLG AM5. The data indicate that PLG with type-I mutation is present in the Chinese Han population, possibly at a polymorphic frequency.

Asian People↗
PubMed1994

Cloning of cDNAs for new subtypes of murine low-affinity Fc receptor for IgE (Fc epsilon RII/CD23).

In humans, two subtypes of the low-affinity Fc receptor for IgE, Fc epsilon RIIa and Fc epsilon RIIb, have been identified. The two forms differ only in a short stretch of amino acids at the cytoplasmic amino terminus. On the other hand, only one Fc epsilon RIIa-like receptor was reported in the mouse, although the existence of another subtype of transcript has been suggested. A new cDNA subtype for murine Fc epsilon RII that has amino acid homology to the human subtype b at the amino terminus was cloned by polymerase chain reaction. When expressed transiently in COS cells, the cDNA is capable of generating a functional cell surface protein that is recognized by an anti-Fc epsilon RII antibody and that has affinity to IgE. In the spleen, although the expression level is considerably lower than that of subtype a, the transcript appears in B cells and in non-B cells upon stimulation with IL-4 and LPS, in contrast to the constitutive expression of the conventional Fc epsilon RII transcript. It is also detectable in several cell lines of B- or T-cell lineages. These results suggest that this gene may be the murine counterpart of human Fc epsilon RII subtype b. Another cDNA clone for the distinct Fc epsilon RII transcript has also been isolated. The cDNA also encodes a surface protein functional on COS cells, but its human counterpart has not been found.

Amino Acid Sequence↗
PubMed1994

Human cytomegalovirus neutralizing antibody response in Japanese children with bone marrow transplantation.

Thirty-two children with bone marrow transplantation (BMT) received intravenous injections of gammaglobulin (IVIG) with a high titer of neutralizing (NT) antibody against human cytomegalovirus (HCMV) (200 mg/kg/week) from 1 week before to 4 months after transplantation. NT antibody titers before BMT and the highest levels in serial determinations conducted after BMT were compared for each patient. They were classified into three groups according to the antibody response: primary HCMV infection as group I, endogenous reactivation or external reinfection as group II, and indeterminable cases as group III. Two (6.3%) out of 32 patients examined had BMT-associated primary HCMV infections, but did not show any clinical symptoms. Significant changes in clinical parameters were also lacking in all the other 30 patients, independent of whether they shed viruses into the urine, or demonstrated on antibody boost. It was concluded from the group variation that the antibody response was indeed due to the engraftment of BMT, rather than to a direct effect of treatment with IVIG. Our results further indicate that passive immunization with HCMV antibody does not prevent infection, but confers some protection against symptomatic disease.

Adolescent↗
PubMed1994

von Recklinghausen's disease with lung cancer derived from the wall of emphysematous bullae.

A 53-year-old male with von Recklinghausen's disease, diagnosed to have metastatic large cell carcinoma in the left supraclavicular lymph node, was admitted for radiotherapy. No other primary lesions were found. Emphysematous bullae in both upper lung fields were seen on chest roentgenograph, and the leucocyte count and G-CSF level were extremely elevated. Later, when metastases appeared, systemic chemotherapy was supplemented, but in vain. An autopsy showed large cell carcinoma of the lung derived from the wall of emphysematous bullae in left lung along with multiple metastases. The presence of von Recklinghausen's disease, emphysematous bullae and lung cancer together are noteworthy.

Carcinoma, Large Cell↗
PubMed1994

[Changes in and factors related to fatigue of in-home caregivers who utilize temporary nursing home assistance].

In order to understand the fatigue of in-home caregivers of the elderly and the remedical effects of temporary nursing home assistance (i.e., "respite care service"), pre- and post-service surveys were conducted on the Cumulative Fatigue Symptoms Index (CFSI) of 34 in-home caregivers who use the respite care service offered by a nursing home in Shizuoka, Japan. The results of these two surveys are as follows: 1) The physical fatigue of caregivers before using the respite service is higher, and caregiver's free time is related to their feelings of fatigue. 2) According to CFSI figures, chronic fatigue, general fatigue, anxiety, depression (p < 0.01), and irritability caused by excessive workload and reduced vitality (p < 0.05) were significantly reduced by the services given. 3) Twenty-seven caregivers, or 79% of the sample, showed some improvement, while the remaining 7 caregivers (21%) showed none. 4) Factors which may have affected the degree of fatigue recovery were shown, including reasons and days for using the respite service.

Aged↗
PubMed1994

[Combination neoadjuvant therapy with continuous intra-arterial CDDP infusion and radiotherapy for locally advanced breast cancer].

Neoadjuvant therapy combined with intra-arterial continuous infusion of CDDP and external radiation was evaluated in a patient with locally advanced breast cancer. Although only MR was observed on the primary tumor, PR was found in several metastatic lymph nodes and daughter nodules. All tumor markers elevated before treatment decreased to normal ranges only by this therapy, and histological damage was also recognized remarkably with a high concentration of free Pt (8.89 micrograms/g) in cancer tissues. Since no severe side effects appeared during the present therapy, extended radical mastectomy with wide skin resection could be performed following additional intra-arterial chemotherapy using 5-FU, epi-ADM and MMC. From this experience, it was suggested that CDDP was an useful drug in the chemotherapy for breast cancer.

Adult↗
PubMed1994

[Cardiac herniation after right sleeve pneumonectomy with partial pericardiectomy].

A 63-year-old male underwent a sleeve pneumonectomy with partial pericardiectomy for a squamous cell carcinoma of the right upper bronchus invading the trachea. The pericardial defect was closed primarily. The initial postoperative course was uneventful until we performed endotracheal suction with bronchoscopy in that evening. After severe coughing, he was noted to have a decrease in blood pressure following bradycardia and premature ventricular contraction. He soon fell in shock. A chest X-ray film revealed the cardiac shadow shifted to the right hemithorax. Immediately he was taken back to the theater and rethoracotomy was performed. The heart was found to have herniated into the right hemithorax. As soon as it was repositioned, his general condition improved. The pericardial defect was repaired with a GORE-TEX patch. He recovered. The cardiac herniation after pneumonectomy is one of the fatal complications unless prompt diagnosis and surgical reduction should be done. Repair of the pericardial defect with strong prosthetic patches and careful postoperative management are indispensable for the prevention of the cardiac herniation after pneumonectomy.

Carcinoma, Squamous Cell↗
PubMed1994

bcr/abl mRNA in leukemic blasts of an unusual patient with acute lymphoblastic leukemia followed after 5-year remission by chronic myelogenous leukemia in blast crisis.

A 13-year-old boy without any previous illness was diagnosed as suffering from acute lymphoblastic leukemia (ALL). After a period of apparent complete remission until 17 years of age, the presence of Ph1 positive cells in bone marrow was demonstrated by karyotype analysis. This finding suggested chronic myelogenous leukemia (CML) because of the absence of blastic changes in bone marrow but mild leukocytosis with basophilia at that time. Six months later he had a relapse (blast crisis) with the appearance of peroxidase negative lymphoid blasts and myeloid surface markers. To make differential diagnosis, leukemia blasts at onset and relapse were examined for rearrangement of immunoglobulin JH gene and bcr/abl fusion mRNA, and were found to have the same JH gene rearrangement pattern and the same bcr/abl mRNA of bcr exon 2/abl exon 2. These results indicate an unusual case of CML which appeared in blast crisis at onset, followed by a long-term remission.

Adolescent↗
PubMed1993

Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene.

Primary hypoalphalipoproteinemia is associated with atherosclerosis and exhibits significant familial aggregation. To reveal the presence of autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene, the apolipoprotein A-I gene was analyzed in a Japanese family with low levels of HDL cholesterol and apolipoprotein A-I. An insertion of a C in the region of the seven C run between codons 3 and 5 was detected in the apolipoprotein A-I gene. The heterozygous state for the mutation was associated with approximately 50% of the normal HDL cholesterol levels and of the normal apolipoprotein A-I levels. The data suggest that a part of familial hypoalphalipoproteinemia might be an autosomal dominant trait due to a completely defective apolipoprotein A-I gene.

Adult↗
PubMed1993

Familial genetic defect in a case of leukocyte adhesion deficiency.

Leukocyte adhesion deficiency (LAD) is an inherited immunodeficiency disorder caused by CD18 subunit abnormality dependent defective expression of beta 2 integrins on the surface of leukocytes. On analysis of the CD18 molecular defect in a female Japanese patient with a severe deficiency LAD phenotype, neither CD11a nor CD18 molecules could be detected on the patient's EBV-transformed B lymphoblastoid cell line. The mRNA of the patient's B cells was normal in size, but was diminished in quantity, to approximately half normal levels. Sequencing of the CD18 cDNA of the patient revealed a C605 to T transition, resulting in a Pro178-->Leu substitution. This was heterozygous in the genomic DNA, and shown to be of maternal origin by family study. Only a few transcripts from the other allele without the Pro178-->Leu mutation were detectable. Northern blot analysis revealed reduced CD18 mRNA levels, not only in the patient, but also in the father and brother. These results indicate that our case is a compound heterozygote with two different mutant alleles: one causing a single amino acid substitution and the other causing defective expression of mRNA.

Amino Acid Sequence↗
PubMed1993

Subacute panencephalitis associated with chronic graft-versus-host disease.

A unique form of subacute panencephalitis developed in a child with aplastic anemia 8 months after an allogeneic bone marrow transplantation (BMT). It was characterized by parenchymal infiltration of CD3 lymphocytes, a marked increase in the number of microglia strongly expressing HLA-DR antigens in both the gray and white matter, and diffuse degeneration of the cerebral white matter. The onset of neurological symptoms coincided with the development of chronic systemic graft-versus-host disease (GVHD). Cellular infiltrates in the CNS lesions were exclusively CD3 lymphocytes intermingled with a small number of monocytes labeled with CD68. There was a preponderance of cells of the CD45RB phenotype. The pathological changes in visceral organs were consistent with those of chronic GVHD. In addition, scrutiny of immunohistochemistry disclosed sparse infiltration of CD3 lymphocytes and diffuse gliosis in the cerebral white matter of another child with chronic GVHD who died 9 months after allogeneic BMT. These cases are suggestive of a potential risk of CNS involvement in GVHD.

Adolescent↗