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Biomedical subjects

Y Sohma

Publications and source records attributed to Y Sohma.

16 recordsLinked to original sources

Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant glioma.

Overexpression of the alpha-Platelet Derived Growth Factor Receptor (alpha-PDGF) gene was detected in a case of malignant glioma. This overexpression was accompanied with amplification of rearranged alpha-PDGF receptor gene. We have isolated a cDNA for the transcript derived from the amplified receptor gene. Characterization of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in the extracellular region of the receptor. This in-frame deletion removed a part of the immunoglobulin-like domains in the extracellular region of the receptor. Analysis of the amplified alpha-PDGF receptor gene in the glioma indicated that exons coding for the 81 amino acids were lost by a gene deletion. The gene amplification was also detected in macroscopically normal cortex adjacent to the glioma from the same patient. However, the amplified gene in the macroscopically normal cortex had no major gene rearrangement. These data suggest that the overproduction of structurally altered alpha-PDGF receptor may take part in the onset and the development of malignant glioma.

Exons

Amplification of alpha-platelet-derived growth factor receptor gene lacking an exon coding for a portion of the extracellular region in a primary brain tumor of glial origin.

In a primary brain tumor of glial origin, we found overexpression of the alpha-platelet-derived growth factor (alpha-PDGF) receptor mRNA. Southern blot analysis of the gene revealed amplification of the rearranged alpha-PDGF receptor gene in the glioma. A cDNA coding for an aberrant transcript from the amplified receptor gene was obtained and characterized. Partial nucleotide sequence analysis of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in a portion of the immunoglobulin-like domains of the extracellular region of the receptor. cDNA polymerase chain reaction (PCR) of the total cellular RNA in the glioma indicated that more than 80% of the transcripts have a deletion of 243 nucleotides. Analysis of a PCR-amplified DNA fragment derived from the amplified alpha-PDGF receptor gene in the glioma revealed that an exon coding for the 81 amino acids was removed by a 2.1 kb gene deletion. We also found amplification of the alpha-PDGF receptor gene in macroscopically normal cortex adjacent to the glioma from the same patient. The amplified gene in the macroscopically normal cortex has no major gene deletion, suggesting that gene amplification is not sufficient for the development of malignant gliomas.

Amino Acid Sequence

Effects of histidine residues on adsorption equilibrium of peptide antibodies.

Histidine and arginine residues in a peptide, which represent residues 112-121 of myoglobin, were replaced by alanine, and antibodies for these peptides were raised in rabbits. Adsorption equilibria between these peptides and antibodies were measured to identify the essential amino acid residues for specific binding and their effects on adsorption behavior. Protonation of one histidine residue affected strongly the dependence of adsorption equilibrium on pH, and the adsorption capacities of the antibodies against the peptides containing this essential histidine residue rapidly decreased at around pH 5-6, which corresponds to the pKa value of histidine. Immunization with peptide sequences containing such histidine residues is one method to obtain suitable antibodies for immunoaffinity chromatography, which have a weak affinity for the elution step under mild conditions.

Adsorption

Decrease in rat submandibular acinar cell volume during ACh stimulation.

Changes in acinar cell volume were measured in the perfused submandibular gland of the rat at 23 degrees C during salivary secretion induced by acetylcholine (ACh). Cellular volume was monitored by two methods: the impedance method and the morphometric method using video-enhanced contrast optical microscopy. Both measurements revealed a decrease in acinar cell volume in response to 1 microM ACh. Within the 1st min of stimulation, secretion increased to the initial maximum (initial secretion), and cell shrinkage occurred. During sustained stimulation, secretory rate and cell volume were maintained at the plateau level (steady secretion). The decrease in cell volume was 71.8 +/- 2.9% of resting volume (means +/- SE, n = 8) as measured by the impedance method and 76.1 +/- 2.0% (n = 20) as measured by the morphometric method. With the removal of ACh, cell volume increased to 111.6 +/- 2.7% (n = 8) of the prestimulation level as measured by the impedance method and 108.8 +/- 1.5% (n = 20) as measured by the morphometric method, and then recovered to the prestimulation level slowly. The weight of the gland decreased significantly during stimulation. These findings proved that volume decrease occurred during stimulation. The measurement of cell volume gave the net fluid flux of the acinar cell compartment. The net fluid flux and the rate of salivary secretion gave an estimation of the fluid influx across the basolateral membrane. These findings suggest that a transcellular route for fluid secretion exists in the salivary gland.

Acetylcholine

[Left ventricular performance following mitral valve replacement in patients with tight mitral stenosis combined with mild aortic regurgitation].

The severity of aortic regurgitation is difficult to estimate prior to mitral valve replacement (MVR) in cases with tight mitral stenosis (MS), because low output state due to mitral obstruction masks signs of aortic regurgitation. This study clarified left ventricular performance, possibly affected by increased diastolic loading after MVR. The study subjects consisted of 12 patients with pure mitral stenosis (MS group) and 11 with combined mitral stenosis and aortic regurgitation (MSAR group). The diagnosis was made by cardiac catheterization preoperatively. The aortographic grade of aortic regurgitation was class 1 or 2 according to the AHA classification. Both groups were matched in terms of severity in mitral obstruction evaluated by mitral valve area. On preoperative echocardiographic evaluation, there was no difference in the mean values of LVDd, LVSd, and %FS between the groups MS and MSAR. After surgery, symptoms improved in each patient. Echocardiography performed three months after MVR revealed no differences in these parameters between both the groups. We concluded that aortic regurgitation evaluated as class 1 or 2 preoperatively does not increase in respect to left ventricular diastolic overloading and echocardiographic left ventricular performance remains unchanged.

Adult

Surgical treatment of the aortic aneurysm.

For 93 cases of thoracic and 118 cases of abdominal aneurysms, the over-all operative mortality rate was 24.7 per cent and 9.3 per cent, respectively. Although the over-all operative mortality rate for 37 patients with aneurysms of the ascending aorta or aortic arch had been 40.5 per cent, recent advances in surgical technique led to a higher survival rate so that since 1975 no death occurred among 14 consecutive surgery cases. Cardiopulmonary bypass with or without selective perfusion of the carotid arteries or temporary external bypass procedures were employed in these 14 cases. The over-all operative mortality rate for 56 patients with aneurysms of the descending thoracic aorta was 14.3 per cent. Temporary external bypass procedures were employed in 49 cases. The operative mortality rate for 99 patients with unruptured abdominal aneurysms was five per cent, and that for 19 patients with ruptured aneurysms was 31.5 per cent.

Adolescent

Surgical indication and results in ventricular septal defect associated with severe pulmonary hypertension.

Sixty-four patients with large ventricular septal defects and severe pulmonary hypertension form the basis of this report. Prior to the end of 1970, 35 patients with a ratio of pulmonary to systemic artery pressure (pp/ps) of 0.8 or more were subjected to primary closure of the defect, resulting in 11 operative deaths Since the beginning of 1971, until March, 1974, however, the surgical results have markedly improved and 29 such patients were operated on without death. It has been our principle to perform elective closure of the defect at the age of 1 to 3 years. An earlier operation was planned when a decrease in the apical diastolic rumble and the size of the enlarged left ventricle on the chest x-ray were found on the periodical observation since infancey. If cardiac failure could not be controlled with medical treatment, primary closure of the defect has been performed even under one year of age.

Adolescent