Search PubMed⌕ Search

Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 631 records · Page 35Linked to original sources

Heat shock gene activation by mutant actin is independent of myofibril degeneration in Drosophila muscle.

Artificially mutagenized Drosophila Act88F actin genes with triple and double mutations were expressed in the indirect flight muscles of transgenic flies. The triple mutant actin, GD245T (Gly-36----Glu, Glu-83----Asp, and Gly-245----Asp), induced heat shock protein (hsp) synthesis without affecting flight ability. On the other hand, the double mutation, GD245D (Gly-36----Glu and Glu-83----Asp), disrupted myofibrils but induced little hsp synthesis. These results demonstrate that myofibril degeneration is not the primary cause of the anomalous heat shock gene activation by mutant actins.

Actins↗

Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells.

Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) is a receptor for the complement component C3b. We have previously isolated HSV-1 gC- strains (TN1, TN2 and TN3) from a patient with recurrent keratitis at three different times. These are very rare isolates because gC was thought to be essential for the virus in vivo. To determine whether gC modifies the interaction of complement with cell-free virus or virus-infected cells, we constructed gC+ recombinant viruses in which the intact gC gene of strain KOS was inserted into the TN1 virus genome. TN1 virus was inactivated by complement and TN1 virus-infected cells were lysed by complement; however, gC+ recombinant viruses became resistant to these effects of complement. These results suggest a role for gC in protection of both the virion envelope and the infected cell surface against damage by complement. TN1 virus was inactivated by complement from rats (Wistar, WKA, F344 and SD), guinea-pigs (Hartley) and humans, but not by complement from mice (C3H, DDD and BALB/c), which indicates that mice seem to be inappropriate as an experimental model for the study of HSV infection in which complement factors need to be considered.

Animals↗

Lower pacemaker in high degree atrioventricular block is modulated electrotonically by atrial excitations.

To see if the lower pacemaker in patients with atrioventricular (AV) block was modulated electrotonically by atrial excitation, we studied R-R intervals in two groups of AV block patients using a phase response curve (PRC). Group I consisted of 20 patients with high degree AV block, including seven patients in whom complete AV block was transiently observed in the course of acute inferior myocardial infarction. Group II consisted of 19 patients with complete AV block. In every patient, PRC was obtained from the continuous electrocardiogram by plotting each R1-R2 interval (response) on the ordinate as a function of the R1-Px interval (phase, x = 1, 2 ...) on the abscissa. In Group I, the R-R interval was prolonged when the P wave fell in the initial half of the R-R interval, and was abbreviated when the P wave fell in the later half of the cycle. In Group II, the fluctuation of the R-R interval was minimum. In ten group I patients, with the improvement of the AV block, PRC became sharper and transition from prolongation to shortening occurred at shorter R-P intervals. We conclude that, in Group I, lower pacemaker was modulated electrotonically by atrial excitations through decreased electrical coupling along the AV node.

Aged↗

Transformation system for an asporogenous methylotrophic yeast, Candida boidinii: cloning of the orotidine-5'-phosphate decarboxylase gene (URA3), isolation of uracil auxotrophic mutants, and use of the mutants for integrative transformation.

An integrative transformation system was established for an asporogenous methylotrophic yeast, Candida boidinii. This system uses a uracil auxotrophic mutant of C. boidinii as the host strain in combination with its URA3 gene as the selectable marker. First, the C. boidinii URA3 gene coding for orotidine-5'-phosphate decarboxylase (ODCase) was cloned by using complementation of the pyrF mutation of Escherichia coli. Next, the host ODCase-negative mutant strains (ura3 strains) were isolated by mutagenesis and selection for 5-fluro-orotic acid (5-FOA) resistance. Five ura3 host strains that exhibited both a low reversion rate and good methylotrophic growth were obtained. All of these strains could be transformed to Ura+ phenotype with a C. boidinii URA3-harboring plasmid linearized within the Candida DNA. The transformants had a stable Ura+ phenotype after nonselective growth for 10 generations. These results and extensive Southern analysis indicated that the linearized plasmid was integrated into the host chromosomal DNA by homologous recombination at the URA3 locus in C. boidinii.

Blotting, Southern↗

Postnatal changes in nerve cells and myelinated fibers in the pineal gland of cotton rats (Sigmodon hispidus). A light microscopic study.

Intrapineal neurons and intracapsular and intrapineal myelinated fibers were studied by light microscopy in male cotton rats (Sigmodon hispidus) at various postnatal ages. Until 300 days of age, neurons are encountered mainly in the distal third of the organ; neuronal nuclei are largest in this region. The remaining regions contain only a few neurons with smaller nuclei. In all regions, nuclear sizes of the neurons increase, and neuronal numbers reduce by half until 100-200 days. Neurons thus consist of different populations of cells, and the aging changes in neuronal nuclei seem to be related to the differentiation of the organ. The disappearance of neurons and the enlargement of the nuclei of remaining neurons proceed simultaneously with age. Intracapsular and intrapineal myelinated fibers appear at 20 days and their density increases with age. As the myelinated fibers are distributed mainly in the distal region and its capsule, these fibers are related topographically to intrapineal neurons. The intracapsular myelinated fibers continue into bilateral bundles of myelinated fibers found under the transverse sinuses, corresponding to the nervi conarii. Since the intracapsular fibers and the fibers traced between the capsule and the parenchyma bifurcate in a proximal direction, the intracapsular fibers are considered to run proximally, some entering the organ.

Aging↗

[Results of myocutaneous flap for extensive skin defect in the external genitalia].

We reviewed 12 patients who underwent myocutaneous flap plasties to reconstruct the genital skin. The patients included 9 who underwent a radical excision of malignant tumor involving the genital, inguinal or sacral skin, 1 with an extensive radiation ulcer of the genitalia and 2 with an ulcerating cancer of the scrotum or groin. In the latter 2 patients the plasty was intended to cover an unresectable ulcerating cancer. A gracilis myocutaneous flap was used in 10 patients, and a tensor fascia lata myocutaneous flap in 2 patients. Postoperatively, partial or total necrosis of the skin of the flap developed in 8 patients. In 4 of these, infection complicated the necrosis. Although debridement, resuture or free skin transplantation was needed in these patients, wound healing was ultimately achieved in 10 patients who underwent radical excision of malignant tumor or radiation ulcer. In contrast, the intended coverage of an unresectable ulcerating cancer was unsuccessful in two other patients. No patients had motor disturbance after wound healing. However, one patient developed stricture of the urethra and vagina which had been opened through the flap, and another patient complained of gait disturbance and difficult defecation because of an swelling of the flap around the anus. Incision or excision was required to relieve the complaints in these 2 patients. These results indicate that a myocutaneous flap is useful to cover an extensive skin defect of the genitalia, but may be accompanied by postoperative complications particularly before wound healing. Appropriate management is necessary to achieve the intended reconstruction.

Aged↗

[A case of thyrotoxicosis with prolonged muscle cramp and hypocalcemia after treatment with methimazole].

We report a case of thyrotoxicosis with prolonged post-treatment muscle cramp and hypocalcemia. A 36 year-old woman with hyperthyroidism was treated with Methimazole (MMI). As plasma levels of T4 and T3 were normalized, hypocalcemia was noted and severe cramp of skeletal muscle appeared so that the patient was unable to walk. The cramp was gradually relieved as the levels of thyroid hormones re-increased by discontinuance of MMI, and recurred as the hormone levels were normalized by readministration of MMI. The plasma levels of free calcium ion was positively correlated with those of thyroid hormones, and the muscle cramp was worsened with lowering of the calcium level. Serum examination also revealed vitamin D-deficiency, which was probably due to an unbalanced diet of the patient. A therapeutic trial with 1 alpha-vitamin D3 and calcium lactate in addition to MMI improved both thyrotoxicosis and muscle cramp. These findings suggested that hypocalcemia due to vitamin D-deficiency was involved in the exceptionally prolonged muscle cramp associated with the treatment of hypothyroidism in this patient.

Adult↗

Exocrine pancreatic function in chronic liver diseases.

To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity.

Amylases↗

[A prospective trial of the mass survey for pancreatic cancer using serum markers and ultrasonography].

We designed a prospective trial of the mass survey for pancreatic disease, especially pancreatic cancer in consecutive 2576 subjects undergoing periodical health examination during 1989. In order to detect abnormality of the pancreas we measured serum amylase, elastase-1 and SPan-1 as serum markers and used ultrasonography (US). When abnormal elevation of serum markers or abnormal findings of US were obtained at the first screening, re-examination or further examination using ERCP, CT and endoscopic US were performed. Frequencies of elevated amylase, elastase-1 or SPan-1 were 0.9%, 3.4% or 1.7%, respectively. However, no pancreatic diseases were detected among the cases of elevated serum markers after subsequent further examination. Frequency of abnormal US findings of pancreas were 2.3% (59/2576), including dilatation of main pancreatic duct, cystic lesion, space occupying lesion and calcification. Subsequent further examinations on subjects with abnormal US revealed 8 cases of pancreatic diseases including one small pancreatic cancer. US may be an efficient tool of mass survey for pancreatic cancer in the health examination at present.

Adult↗

Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C.

Hepatitis C virus RNA as detected by reverse transcription and nested polymerase chain reaction was monitored in 16 patients with chronic hepatitis C treated with interferon. Hepatitis C virus RNA became undetectable after 4 to 8 wk of interferon administration in 13 of the 16 patients. During 6 mo of follow-up, 5 of the 13 patients who became negative for hepatitis C virus RNA after interferon administration remained negative, and all five continued to have normal ALT levels. Repeat liver biopsy in these five patients revealed histological improvement. Antibody to hepatitis C virus, which was initially positive in all treated patients, fell to undetectable levels in three of the five patients. In contrast, aminotransferase levels rose again in all eight patients who had become hepatitis C virus RNA negative but had again exhibited hepatitis C virus RNA after completion of therapy. In 16 untreated patients, hepatitis C virus RNA remained detectable. These results indicate that detection of hepatitis C virus RNA may be useful as a marker of viral replication in chronic hepatitis C; they also suggest that interferon should again be administered to patients who become hepatitis C virus RNA negative on treatment but again exhibit this marker of viral replication when treatment is stopped.

Adult↗

[Diagnostic value of serum level of alpha 2-macroglobulin-trypsin complex in pancreatic diseases using a colorimetric assay with a synthetic chromogenic substrate].

We measured serum level of alpha 2-macroglobulin-trypsin complex (alpha 2M-T complex) using a colorimetric assay with a synthetic chromogenic substrate, D-gamma-tert-butyloxy-Gly-Arg-3-carboxy-4-hydroxyanilide dihydrochloride. Serum level of alpha 2M-T complex was greater in acute pancreatitis patients than in chronic pancreatitis or pancreatic cancer patients. In severe acute pancreatitis patients, both mean level and frequency of abnormal value of serum alpha 2M-T complex were significantly greater than in mild acute pancreatitis patients (13.1 +/- 12.9 vs 2.9 +/- 3.5 U/L, p less than 0.01; 100 vs 41%, p less than 0.01). In conclusion, the determination of serum level of alpha 2M-T complex can be useful for the diagnosis of severe acute pancreatitis.

Acute Disease↗

Gene amplification of Japanese non-Hodgkin lymphoma with involvement of the BCL2 gene.

Twenty cases of Japanese non-Hodgkin's lymphoma with B cell markers were studied with respect to their immunoglobulin heavy (IgH) chain gene loci on chromosome 14 and BCL2 loci on chromosome 18. All of the 20 cases showed IgH gene rearrangement on at least one of the alleles. Molecular analysis using two chromosome 18-specific DNA probes (pFL1 and pFL2) showed rearrangement of the BCL2 region in three of 20 cases. As these three samples showed the rearranged allele of the IgH gene comigrating with that of the BCL2 gene, polymerase chain reaction (PCR) was carried out to amplify the juncture between IgJH on chromosome 14 and BCL2 on chromosome 18. In all of these three cases, gene amplification between the two loci was found to occur, indicating that molecular mechanisms involved in this type of chromosomal translocation in Japan might be similar to cases in the United States (U.S.) in a limited number of cases. Furthermore, this amplification technique revealed minimal tumor cells circulating in peripheral blood, even though lymphoma cells could not be identified morphologically. Thus, the PCR technique is useful for both the detection of minimal tumor cells as well as for the determination of the molecular nature of chromosomal translocation in some of Japanese cases.

Base Sequence↗

Global and regional abnormalities of left ventricular diastolic filling in hypertrophic cardiomyopathy.

Left ventricular diastolic filling was studied by left ventriculography in 17 patients with hypertrophic cardiomyopathy (HCM). In 8 patients this manifested as a spadelike shape (HCM-S type) on the left ventriculogram, and in 9 patients as a banana shape (HCM-B type). Seven patients were studied as controls. Left ventricular end-diastolic pressure was higher in HCM than in controls. In HCM, peak filling rate was decreased from 1.57 +/- 0.28 of the control to 1.28 +/- 0.20 (p less than 0.05), and the time to peak filling rate was prolonged from 27 +/- 6%DT of the control to 37 +/- 7%DT (p less than 0.01). Serial volume analysis in diastole showed filling fraction was also significantly decreased to 8.2 +/- 4.1 (p less than 0.001) at the 25% diastole time and 29.6 +/- 7.2 (p less than 0.01) at half time, compared with 19.8 +/- 6.3 and 32.8 +/- 5.8 for controls, respectively. In HCM-S type, the rate of distention of left ventricular radial axes at the apical area was lower at early and mid-diastole. In HCM-B type, the rate at the basal area was lower at early and mid-diastole. Results suggest that the left ventricular diastolic filling in HCM was impaired not uniformly but regionally in the hypertrophic area at early and mid-diastole.

Adult↗