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Biomedical subjects

Y Yuasa

Publications and source records attributed to Y Yuasa.

At least 181 records · Page 10Linked to original sources

Distribution of basal lysosomes in exocrine acinar cells.

We examined the distribution of trimetaphosphatase (TMPase)-positive basal lysosomes in pancreas, parotid, submandibular, sublingual, and exorbital lacrimal glands from rats, rabbits, and guinea pigs. The location of the basal lysosomes was compared to that of the acid phosphatase (AcPase)-positive lysosomes. In all of the tissues examined from rat and rabbit, AcPase activity was localized primarily to the Golgi region. Reaction product was localized in GERL, immature secretory granules, and lysosomes lying adjacent to the Golgi apparatus. TMPase activity was found in basal lysosomes and in occasional elongated lysosomes adjacent to the Golgi apparatus. In guinea pig, the distribution of TMPase activity was identical to that seen in the other two species, but a significant number of lysosomes in the basal region of the cells also contained AcPase activity. These results confirm and extend our previous finding (J Histochem Cytochem 31:1209, 1983) that exocrine acinar cells possess two distinct populations of lysosomes. The lysosomes in the Golgi region contain both AcPase and TMPase activity, whereas those in the basal portion of the cells are reactive predominantly for TMPase. The functional significance of the two populations of lysosomes is not understood at present.

Acid Anhydride Hydrolases↗

Transforming genes in human hepatomas detected by a tumorigenicity assay.

Two transforming sequences in human hepatomas were detected by means of a tumorigenicity assay in nude mice using transfected NIH3T3 cells. Through hybridization with known oncogene probes, the transforming gene in one hepatoma was found to be the human hst gene. The transforming sequence in the other hepatoma showed no sequence homology with any of the oncogenes examined.

Animals↗

Effects of interventricular shunt on indices of left ventricular function.

The accuracies of indices of left ventricle function were examined in an open-chest model in dogs with and without a ventricular septal defect, in which the ventricular shunt was opened and reclosed by a specially designed flowmeter probe with a cap. The systolic time interval, the maximal rate of pressure development in the left ventricle (+LV dP/dt), +LV dP/dt corrected for the isometric pressure (+LV dP/dt/Pd), and the time to +LV dP/dt (t-dP/dt) were determined by recording the aortic flow, ventricular shunt flow, aortic pressure, pulmonary arterial pressure, and left ventricular pressure. The isometric contraction time, the preejectional period, and the ejection time shortened with decrease of the mean aortic pressure and aortic flow, and the mean pulmonary arterial pressure increased after opening the ventricular shunt. When the pulse was varied by atrial pacing, the systolic time interval was affected in dogs both with and without a ventricular septal defect, but "isometric contraction time" was not affected in animals with a ventricular septal defect. Dopamine and methoxamine were used to evaluate the effects of the inotropic state and afterload on these indices. The extents of the changes in the systolic time interval and +LV dP/dt were different in animals with and without a ventricular septal defect, but the changes in preejectional period/ejection time, +LV dP/dt/Pd and t-dP/dt were similar in the two conditions. These results suggest that the systolic time interval and the indices of left ventricular pressure are useful in assessment of cardiac function only in certain conditions.

Animals↗

Change in pulmonary and systemic circulation in acute ventricular septal defect.

The correlation between left to right ventricular (L-R) shunt flow and other hemodynamic changes was studied in 16 dogs with an acute ventricular septal defect (VSD) and normal pulmonary vascular bed. The interventricular shunt flow was measured directly with a specially designed electromagnetic flowmeter probe, where the area of the VSD was constant. The sudden presentation of VSD increased pulmonary arterial pressure, pulmonary flow and left ventricular end-diastolic pressure. L-R shunt flow was not changed significantly by atrial pacing except when the rate was increased to over 200/min. Dogs with a VSD were treated with isoproterenol and dextran to vary the shunt flow and hemodynamic parameters. L-R shunt flow was decreased by isoproterenol and increased by dextran loading. The percentage changes of L-R shunt flow from pre-drug values correlated well with the change in left ventricular end-diastolic pressure (r = 0.75) and the ratio of pulmonary to systemic vascular resistance (r = -0.73). Change in total pulmonary vascular resistance had a greater effect on L-R shunt flow than did a change in systemic vascular resistance, whereas a change in aortic flow had less effect (r = 0.35) on L-R shunt flow than did a change in preload and afterload. The time to peak LV dP/dt, as an index of cardiac contractility, and heart rate were not correlated with the relative change in L-R shunt flow. These results indicate that L-R shunt flow induced by the sudden presentation of a VSD varied with changes in the pulmonary and systemic circulation.

Animals↗

Activated N-ras in a human rectal carcinoma cell line associated with clonal homozygosity in myb locus-restriction fragment polymorphism.

An N-ras transforming gene was detected in human rectal carcinoma-derived cells (7060) and molecularly cloned. The genetic lesion responsible for the transforming activity of the 7060 oncogene was localized to a single nucleotide transition from A to T in codon 61 of the predicted protein. This lesion in the second exon results in substitution of histidine for glutamine at this position. We also found an EcoRI restriction fragment length polymorphism, consisting of two alleles, of the human c-myb gene. The 7060-transformed epithelial cells showed the homozygous phenotype, while normal fibroblasts of the same patient showed the heterozygous phenotype. This suggests a relationship between the phenotypic change in the c-myb locus and the induction of the 7060 tumor.

Carcinoma↗

Colon carcinoma K-ras 2 oncogene of a familial polyposis coli patient.

The DNA of a colon carcinoma-derived cell line (KMS-4) and that of skin fibroblasts from a familial polyposis coli patient were transfected into NIH3T3 cells in order to detect oncogenes associated with the disease. No transformation was observed with the normal skin fibroblast DNA, while the KMS-4 cell DNA was able to transform NIH3T3 cells. Through hybridization with known oncogene probes, the KMS-4 transforming gene was found to be a human activated c-K-ras 2 oncogene. Sequence analysis of the molecularly cloned KMS-4 c-K-ras 2 oncogene showed a single nucleotide transition from G to T at the 12th codon. This results in substitution of cysteine for glycine at this position. On using labeled synthetic oligonucleotides to detect the mutation in codon 12, we found the G to T transition in colon carcinoma cells. This suggests that activation of the c-K-ras 2 oncogene could be associated with colon carcinoma induction.

Adenomatous Polyposis Coli↗

[Clinical studies on cefixime in pediatrics].

A clinical study of cefixime (CFIX), a new oral cephalosporin, was carried out to evaluate its therapeutic effectiveness on bacterial infections in children. CFIX was orally administered to 13 patients including 6 with upper respiratory tract infection (RTI), 3 with pneumonia, and 1 each with bronchitis, otitis media, skin abscess, and urinary tract infection (UTI). The daily dosage per kg bodyweight ranged from 5.1 to 17.4 mg (average: 8.7 mg), and was given in 2 or 3 divided doses per day for 3 to 10 days (average: 5.8 days). The clinical response was excellent in 4 (30.8%), good in 7 (53.8%) and poor in 2 (15.4%), with an overall efficacy rate of 84.6%. Bacteriological efficacy was good, and 6 of the 8 identified causative organisms were eradicated. Side effects were observed in 3 children, i.e., loose stool in 1 and transient elevations of GOT and GPT in 2. The above results suggest that CFIX is a useful new oral cephalosporin for the treatment of bacterial infections in children.

Bacteria↗

Effects of two major activating lesions on the structure and conformation of human ras oncogene products.

ras oncogenes are frequently activated in human tumors by mutations at codon 12 or 61 in their coding sequences. To investigate how these subtle alterations exert such profound effects on the biologic activities of these genes, we studied structural and conformational properties of human ras-oncogene-encoded 21-kDa proteins (p21s). We observed striking differences in the electrophoretic mobilities of the proteins under reducing and nonreducing conditions. These findings imply that intramolecular disulfide bonds affect native p21 conformation. The two activating lesions were shown to induce distinctly different alterations in p21 electrophoretic mobility that were unmasked only under reducing conditions. These results suggest that regions of the molecule containing such alterations are either not exposed or under conformational constraints in the native p21 molecule. We confirmed the opposing effects on protein mobility induced by the two activating lesions by using a recombinant gene containing both lesions. The recombinant gene's high-titer transforming activity further established that the two lesions do not negatively complement one another with respect to transforming-gene function. Our findings of distinct alterations in electrophoretic mobilities of position-12- and position-61-altered p21 molecules should be applicable to the rapid immunologic diagnosis of ras oncogenes in human malignancies.

Amino Acid Sequence↗

Magnetic resonance imaging of fluorine in rats infused with artificial blood.

An MRI pulse sequence has been developed that enables the visualization of a perfluorocarbon (PFC) emulsion in the vascular system of rats. Images were made at 0.12T on a clinical imaging system using a small receiver coil, at intervals of approximately 2 hours, two days, two weeks, and two months after replacement of 50% of total blood volume. The most successful technique produced PA projections of the entire torso for both the fluorine and proton components. Direct comparison allowed identification of PFC in heart, lung, liver, spleen, and large vessels both in vivo and postmortem. Potential clinical applications to vascular imaging are discussed.

Animals↗

Magnetic resonance imaging following unilateral occlusion of the renal circulation in rabbits.

Magnetic resonance studies at 0.12 T were performed following acute unilateral occlusion of the renal artery or vein in rabbits. Prior to occlusion, in vivo and in vitro relaxation times of the renal cortex and outer medulla were similar. After venous occlusion, T1 and T2 were prolonged on the occluded side, while the contralateral side remained unchanged. After arterial occlusion, the outer medulla of both the occluded and contralateral kidney exhibited prolonged relaxation times. There was a significant linear correlation between T1, T2, and the water content of the tissue. The authors conclude that quantitative in vivo relaxation times may eventually prove to be useful in diagnosis, although at present they are less reliable than those obtained in vitro.

Animals↗

Effect of respiratory acidosis on ventricular shunt flow and hemodynamics in dogs with ventricular septal defect.

The effects of respiratory acidosis on ventricular shunt flow and hemodynamics were studied in 20 anesthetized dogs with a ventricular septal defect and a normal pulmonary vascular bed. The interventricular shunt flow was measured directly by using a specially designed electromagnetic flow probe. Respiratory acidosis was produced by hypoventilation and tachypnea with constant minute volume. Hypoxemia was also induced by hypoventilation, but not by tachypnea with constant minute volume. Systemic vascular resistance was increased in severe hypoventilation at 100 and 50 ml of tidal volume, and tachypnea at 100 ml of tidal volume. However the increase of pulmonary vascular resistance was observed in only severe hypoventilation: arterial pH 6.9, PaO2 24 mmHg, and PaCO2 88 mmHg. Left to right ventricular shunt flow and pulmonary blood flow were increased significantly with no change of systemic blood flow in both conditions of respiratory acidosis. The diastolic fraction of shunt flow was increased significantly. These findings indicate that the increase of left to right shunt flow in respiratory acidosis might be one of the risk factors of congestive heart failure for the patients with ventricular septal defect.

Acidosis, Respiratory↗

[Clinical experience with ceftizoxime suppositories in bacterial infections in children].

A clinical trial of ceftizoxime suppositories (CZX-S) was performed to evaluate the therapeutic effectiveness in children with bacterial infection. The subjects were 10 children comprising 4 with pneumonia, 3 with lacunar tonsillitis, 2 with pharyngitis, and 1 with UTI. They were given 1 suppository containing either 125 mg or 250 mg of CZX 2 to 4 times a day. The daily per kg body weight dose ranged from 17.1 to 60.0 mg. The result was "markedly effective" in 3, "effective" in 6, and "failure" was recorded in 1. Bacteriologically, successful eradication of causative organisms was confirmed in all the 4 children who underwent the test. No clinical side effects were observed. The only laboratory test abnormality recorded in a single patient was eosinophilia, which was not definitely ascribable to CZX-S. In conclusion, CZX-S have proved to be a clinically safe and effective antibiotic preparation in infantile infection, even in children whose treatment with conventional antibiotics is associated with difficulties.

Bacteria↗

Mechanism of activation of an N-ras oncogene of SW-1271 human lung carcinoma cells.

An N-ras-related transforming gene was detected in the human lung carcinoma cell line SW-1271 and molecularly cloned. The lesion responsible for its acquisition of transforming activity was localized to a single nucleotide transition from A to G in codon 61 of the predicted protein. This lesion in the second exon results in the substitution of arginine for glutamine at this position. These findings, together with previous studies, indicate that the activation of ras oncogenes in human tumors is most commonly due to point mutations at one of two major "hot spots" in the ras coding sequence.

Amino Acid Sequence↗

A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient.

Among 21 human mammary tumors analyzed for transforming genes by transfection of NIH/3T3 cells, only DNA of a carcinosarcoma cell line, HS578T, registered as positive. A Harvey (H)-ras oncogene identified in this line was cloned in biologically active form and the activating lesion was identified as a single nucleotide substitution of adenine for guanine in the 12th codon. This results in substitution of aspartic acid for glycine at this position of the p21 coding sequence. Knowledge that this alteration creates a restriction site polymorphism for Msp I/Hpa II in the H-ras protooncogene made it possible to survey for the presence of the activated H-ras allele in normal cells as well as in clonally derived tumor cell lines of the same patient. We demonstrated the presence of unaltered H-ras alleles in normal HS578 cells. In contrast, every clonally derived HS578T tumor cell line analyzed contained the H-ras oncogene possessing the genetic alteration at position 12. These findings establish that activation of this oncogene was the result of a somatic event selected within all HS578T tumor cells.

Amino Acid Sequence↗