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Biomedical subjects

H Yasui

Publications and source records attributed to H Yasui.

At least 289 records · Page 16Linked to original sources

Sigma region located between C mu and C delta genes of human immunoglobulin heavy chain: possible involvement of tRNA-like structure in RNA splicing.

Noncoding regions within the cluster of immunoglobulin heavy chain constant genes in the human genome contained a number of repeats. In the mu-delta intron, two repeating units were contained. One 442-base-long fragment located JH-mu intron (defined as "sigma mu(sigma mu)") occupied the position in the mu-delta intron. The other 1166-base-long fragment located somewhere in front of S (class switch) region of C gamma gene was also found in the mu-delta intron. We defined the repeats in the mu-delta intron as "SIGMA (sigma)". The polarities of the longer repeats in the genome were opposite between the mu-delta intron and the upstreams of C gamma genes. These inverted copies (defined as sigma gamma 3 and sigma gamma 4), located 6 kb upstream of their respective C gamma's, were apparently transcribed in vitro, via RNA polymerase III and transcripts should have contained tRNA-like structures. Small DNA fragments capable of encoding tRNA-like structures were also found in corresponding regions of mouse Ig C gamma cluster.

Animals↗

Tryptophan degradation in transplanted tumor cells undergoing rejection.

The depletion of an essential amino acid, tryptophan, caused by indoleamine 2,3-dioxygenase induction in vitro, has been shown to be due to a mechanism that is used in self-defense against inhaled microorganisms and tumor growth. In this communication, we report the results of measuring dioxygenase activity in the peritoneal exudate cells and tumor cytotoxicity at the transplantation loci after in vivo transplantation of tumor cells into the peritoneal cavity of syngeneic or allogeneic strains of mice. The enzyme was induced only when the tumor cells were being rejected from allogeneic animals and no change was observed when the cells continued to grow in syngeneic animals. Furthermore, when the syngeneic tumor cells in a diffusion chamber were i.p. transplanted simultaneously with i.p. injection of allogeneic tumor cells, the enzyme was induced not only in allografted tumor cells but also in the syngeneic tumor cells. Under these conditions, the tumor cells in the diffusion chamber ceased to grow and 50% of the cells were rejected. To determine the type of cells containing the induced enzyme, the peritoneal exudate cells (tumor cells and host cells--mostly small lymphocytes) were separated into six fractions by sedimentation under gravity and by differential centrifugation. Approximately 80% of total enzyme activity was localized in a tumor-rich fraction (98.9% purity), whereas only 0.2% of the activity was found in a lymphocyte-rich fraction (99.5% purity). The localization of indoleamine 2,3-dioxygenase in the tumor cells was confirmed by complement-dependent lysis with specific antibodies against tumor and host cells.

Animals↗

At least five DH genes of human immunoglobulin heavy chains are encoded in 9-kilobase DNA fragments.

The variable region of immunoglobulin (Ig) heavy chain is encoded by three separate genes: variable (VH), diversity (DH) and joining (JH) genes on the germ-line genome. In mice, most complementarity determining region (CDR) III of the heavy chains of myelomas and hybridomas sequenced so far can be assigned to one of the 12 already identified germ-line DH genes by the homology of nucleotide sequences of DH gene-coding regions although extranucleotides, the so-called N segments, are found at the boundaries between DH and JH as well as VH and DH. On the other hand, Siebenlist et al. (Nature 1981. 294:631) identified two DH gene families in human genome: DHQ52, located at 45 bp upstream of the JH gene cluster, and another family encoded at 9-kb regular intervals possibly between VH and JH gene clusters. However, the somatic DH sequences found in VH-DH-JH structure (the somatic DH segment being defined as the region which is not encoded either by germ-line VH or JH gene) are relatively long and apparently random, and do not seem to have the homology to any of the germ-line DH sequences. To explain the origin of high diversity in the CDR III of human Ig heavy chains, Siebenlist et al. predicted the presence of another mechanism, namely DH-DH joinings. In the present study, we identified five DH genes in one of the above 9-kb repeats. This suggests that the total number of germ-line DH genes is much higher in man than in mouse. The comparison between somatic DH sequences and germ-line DH sequences indicates that most somatic DH sequences in human Ig heavy chains are also produced by VH-DH and DH-JH joinings without the joining of multiple DH gene segments.

Antibody Diversity↗

Abnormalities in DNA rearrangements of immunoglobulin gene loci in precursor B cells derived from X-linked agammaglobulinemia patient and a severe combined immunodeficiency patient.

In an attempt to characterize the genes that cause immunodeficiencies such as X-linked agammaglobulinemia (XLA) and severe combined immunodeficiency (SCID) we established precursor B-cell lines by transforming the patients' bone marrow cells with Epstein-Barr viruses. DNA rearrangements of immunoglobulin JH gene loci were observed on both chromosomes in pre-B cells derived from an XLA patient. We cloned and characterized both rearranged bands from one cell line. Both of the rearrangements occurred between DH and JH gene loci without the VH-DH structure. On the other hand, JH gene loci retained the germline configuration on both chromosomes in almost all the transformants derived from a SCID patient that had been determined according to their surface markers, to be in an early precursor B-cell stage. The implications of the observations are discussed.

Agammaglobulinemia↗

Cerebral autoregulation during deep hypothermic nonpulsatile cardiopulmonary bypass with selective cerebral perfusion in dogs.

We evaluated effects of hypothermic cardiopulmonary bypass on the cerebral circulation and metabolism of six dogs over a temperature range of 37 degrees to 20 degrees C under alphastat acid-base regulation (uncorrected for body temperature). Cerebral metabolic rate for oxygen was determined from the difference between arterial and sagittal sinus blood oxygen contents, and direct cerebral blood flow measurements of the venous outflow from the isolated sagittal sinus. After core cooling at a constant perfusion flow rate of 80 ml/kg/min, cerebral blood flow significantly reduced to 10.0 +/- 1.1 ml/100 gm/min at 20 degrees C (20% +/- 2% of that at 37 degrees C) because of an increase in the cerebral vascular resistance (339% +/- 48%). Cerebral metabolic rate for oxygen reduced to 18% +/- 2%. The upper body vascular resistance decreased to a greater extent than the lower body resistance (37% +/- 4% versus 82% +/- 12%). In the selective cerebral perfusion system at 20 degrees C, when perfusion pressure (mean carotid arterial pressure minus central venous pressure) was lowered from 90 mm Hg by graded reduction of the perfusion flow rate, cerebral blood flow remained constant down to a perfusion pressure of 40 mm Hg, then steeply declined. Cerebral metabolic rate for oxygen also kept a constant level down to 30 mm Hg, then fell abruptly. Definite autoregulatory response was detected even in profound hypothermic nonpulsatile cardiopulmonary bypass. These results suggest that cerebral perfusion flow should be regulated so as to keep the perfusion pressure within the range of cerebral autoregulation to prevent cerebral ischemia or hyperperfusion, especially during selective cerebral perfusion for operations on the aortic arch.

Animals↗

[A case of leukoencephalopathy caused by HCFU].

After a hysterectomy, a bilateral salpingo-oophorectomy, two courses of intra-peritoneal chemotherapy of Cisplatinum, Carmofur (HCFU, 600 mg/day [per os]) were given a patient who had ovarian granulosa cell tumor (malignant, stage Iai). Dizziness and loss of consciousness developed about 60 days after administration of HCFU, and leucoencephalopathy was diagnosed. A CT revealed a diffuse low density area in the white matter of the cerebrum. Myelin Basic Protein in the spinal fluid was found to amount to 9.8 mg/dl, which in norm. person is less than 4.0 mg/dl. Also, it showed parallel changes with the course of the clinical findings. HCFU easily dissolves to fat and changes to 5-FU without enzymes in the liver cell. Further HCFU also passes through Blood Brain Barrier to Produce 5-FU and its derivatives, in which the alpha-Fluoro-beta-Alanine is thought to be the culprit that brings on leucoencephalopathy. Even so, HCFU should be dosed when needed in spite of this risk. Other 5-FU modifiers also have been reported to produce the same effect in several cases.

Adult↗

To what extent does the size of a ventricular septal defect correlate with haemodynamic data derived from cardiac catheterisation?

A simplified model based on Gorlin's formula was used to derive an index of the cross sectional area of ventricular septal defects from commonly used cardiac catheterisation data. This index was compared with the area of the defect measured during operation and expressed as a ratio to the cross sectional area of the aorta. The highly significant linear relation (r = 0.94) between this index of the defect area and the size of the defect measured at operation means that the severity of a ventricular septal defect can be assessed from haemodynamic data obtained at cardiac catheterisation.

Adolescent↗

Primary repair of interrupted aortic arch and severe aortic stenosis in neonates.

Two infants, aged 36 days old (Case 1) and 18 days old (Case 2) with interrupted aortic arch types B and A, respectively, and with severe aortic stenosis, were successfully operated on by use of pulsatile cardiopulmonary bypass. The great arteries were normally related in Case 1 and were transposed in Case 2. Repair involved the following procedure: ligation of the patent ductus arteriosus, restoration of aortic continuity with an 8 mm polytetrafluoroethylene graft, placement of an internal patch to tunnel all left ventricular blood from the left ventricle through the ventricular septal defect into the pulmonary artery in Case 1 and patch closure of the ventricular septal defect in Case 2, transection of the main pulmonary artery, anastomosis between the proximal pulmonary artery and the ascending aorta, and interposition of a valved conduit between the right ventricle and the distal pulmonary artery. The operative field could be approached easily through a median sternotomy. Postoperative cardiac catheterization revealed satisfactory anatomical and hemodynamic results in both cases.

Aorta↗

Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients.

Human lungs bearing cancer (n = 27) exhibited up to an approximately 20-fold [on average approximately 5-fold (P less than 0.005)] increase in the enzyme activity that degrades tryptophan to form formylkynurenine, in comparison with lungs with benign lesions (blebs) (n = 7) taken as controls. On the basis of molecular and kinetic properties, this activity was ascribed to indoleamine 2,3-dioxygenase (IDO) [indoleamine:oxygen 2,3-oxidoreductase (decyclizing)]. In vitro studies with human lung slices revealed that human interferon gamma (IFN-gamma) induced the de novo synthesis of IDO dose dependently (10-10(4) units/ml), and at maximum the activity reached nearly 100 times that in the control lungs described above. Human IFN-alpha also served as an inducer, but it was two to three orders of magnitude less potent than IFN-gamma relative to the antiviral titers, suggesting that IFN-gamma is the main mediator of the IDO induction. IDO thus induced in slices avidly metabolized tryptophan in situ: Upon a 24-hr incubation of lung slices pretreated with varied doses of IFN-gamma (10-10(3) units/ml), up to 96% of the tryptophan in the slices was depleted and up to 70% of the tryptophan in the medium was converted, mainly to formylkynurenine, kynurenine, or both. The foregoing results suggest that an IFN-mediated induction of IDO also takes place in vivo in human lungs as a response to cancer, leading to metabolic consequences such as depletion of tryptophan and accumulation of (formyl)kynurenine, which may provide a unique host defense mechanism.

Cycloheximide↗

Strumal carcinoid of the ovary. A case report.

The case of a 58-year-old Japanese female with strumal carcinoid of the ovary is described. Ultrastructural examinations revealed numerous neurosecretory-type granules in the cytoplasm of both thyroid and carcinoid components. Immunohistochemical studies showed immunoreactivities for thyroxin and thyroglobulin in the thyroid component. Several mucous glands were also observed in the tumor tissue. These morphological findings suggested that the follicles in the thyroid component were lined with thyroid follicular, carcinoid and mucous cells, and also supported the theory that this tumor may be derived from multidirectional differentiations of endodermal origin.

Carcinoid Tumor↗