Biomedical subjects
Publications and source records attributed to S Yoshida.
We think that death at home has increased among patients from our hospital due to following factors: 1) solid cooperation with visiting nurse stations, 2) progress in judgments of care ability, 3) changes in family consciousness, 4) enrichment of other support systems for home care.
We investigated late aneurysmal recurrence in 71 patients who underwent direct operations for intracranial aneurysms during the period from 1981 to 1988 and were under 50 years old at the time of operation with ADL rating of 1 or 2 at discharge. And out of the 71 patients, four had already sustained reattack of SAH and been confirmed to have recurrent anuerysms. Another two had been diagnosed as harboring unruptured recurrent aneurysms. Cerebral angiography was carried out for nine patients in the remaining 63, revealing aneurysmal recurrence in four patients. Overall, 14 recurrent aneurysms, 11 de novo and 3 regrowth aneurysms, have been found in 10 patients. Considering the high risk of aneurysmal recurrence, postoperative long-term follow-up including MRA and angiography is mandatory, especially for relatively young patients.
In our attempt to find characteristic genetic changes in resistant tumors, we screened the whole genome for gene aberrations in 28 primary ovarian cancers, using the comparative genomic hybridization (CGH) method. These cancers included 14 tumors from patients who did not respond to cisplatin-based combination chemotherapy in comparison with 14 tumors from patients who completely responded to the chemotherapy. We found gains in chromosomal region 1q21-q22 and 13q12-q14 to be related to the drug-resistant phenotype in ovarian cancer patients. Several genes encoding transcription factors, oncogenes, cell cycle regulators and regulators of the apoptotic pathway are found to be located on these regions of the chromosomes, and these genes are potential modulators for toxic insults in cancer cells. This is the first report that shows the relationship between certain genomic aberrations and clinical resistance for cisplatin-based chemotherapy in ovarian cancer patients based on the CGH analysis. Present findings suggest that these chromosomal gains may be potential indicators for prediction of resistance in ovarian cancer patients prior to cisplatin-based chemotherapy.
The catalytic subunit of human DNA polymerase (pol) delta, p125, was expressed in recombinant baculovirus-infected insect cells, separated from a baculovirus-encoded DNA polymerase, and was purified to homogeneity by affinity trapping with a histidine-octapeptide at the C-terminus of p125 as the ligand. Purified p125 showed DNA polymerase activity resembling conventionally purified calf thymus pol delta. However, the two differed in four ways: 1) the specific activity of recombinant p125 was one quarter of the calf thymus pol delta; 2) the recombinant p125 was relatively resistant to aphidicolin; 3) the apparent Km for dTTP of the recombinant p125 was estimated at 33 microM, 15-fold the value for calf thymus pol delta; and 4) the recombinant p125 was not stimulated by recombinant PCNA, while activity of calf thymus pol delta increased 150-fold in response. Furthermore, PCNA did not stimulate either the p125 incubated with p50, a small subunit of pol delta, or co-expressed with p50 in insect cells. The full length recombinant p125 migrated slightly faster than pol delta from human cell lines, Jurkat or HeLa, upon SDS-polyacrylamide gel electrophoresis, suggesting a post-translational modification. The results indicate that in vivo assembly of the fully active complex of pol delta requires factors in addition to p125 and p50 subunits, and/or a post-translational modification of p125.
A 57-year-old woman had been diagnosed as systemic sclerosis (SSc) with Raynaud's phenomenon, acrosclerosis and polyarthritis since 1995. She admitted to our hospital in July 1996 because of general fatigue, hemosputa and progressive renal insufficiency. On admission, the blood pressure was normal and laboratory findings showed elevation of the serum creatinin level and a high titer of the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) (> 1000 EU). The renal biopsy revealed crescentic glomerulonephritis. Both renal insufficiency and high titers of MPO-ANCA improved remarkably after methylpredonisolone pulse therapy. This case was suggestive of elucidating the pathogenesis of SSc and MPO-ANCA related glomerulonephritis.
BACKGROUND: Cerebrovascular disease and cervical artery diseases are potentially treatable conditions that are associated with an increased incidence of stroke after cardiac surgery. This prospective study was designed to determine the prevalence of cerebrovascular diseases in the high risk population of cerebrovascular event including some young patients in Japan and establish the strategy for cardiac surgery of patients with cerebrovascular disease. METHODS: 100 (71 male, 29 female) of 126 consecutive patients undergoing cardiac surgery under cardiopulmonary bypass were screened for the presence of cerebrovascular disease by intra-arterial angiogram. RESULTS: In seven patients angiographic evaluation disclosed some evidence of cerebrovascular disease for 50% or greater stenosis or cerebral aneurysm. Preoperative 99mTc-Hexamethyl propylene amino oxime (99mTc-HMPAO) single emission computed tomography (SPECT) with combination of balloon arterial occlusion test provided detailed information of cerebral ischemic tolerance and reliable decision making for surgical repair of cerebrovascular disease. No deaths were recorded and a small stroke in one patient. CONCLUSIONS: We concluded that cerebrovascular screening in patients with cardiovascular disease may be requested in a high risk population of cerebrovascular events.
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In order to elucidate the molecular mechanism(s) for BCL6 translocation, we identified translocational partner genes by subjecting clinical biopsy samples from patients with non-Hodgkin's lymphoma to 5'-rapid amplification of cDNA ends (5'-RACE). Sequence analysis of the 5'-RACE product revealed that the BCL6 gene was fused to the J segment of the immunoglobulin heavy chain (IgH) gene in about half of the cases, but in the other half, it was fused to heterologous partners, including the MHC class II transactivator (CIITA), pim-1, eukaryotic initiation factor 4AII (eif4AII), transferrin receptor (TFRR) and ikaros genes. Since analyses using genomic long and accurate (LA) - PCR revealed that the breakpoints in the partner gene were confined to the first intron or the second exon in all cases, the promoter and the first exon of the BCL6 gene were replaced by the promoter and the first or both the first and second exon of the partner gene. The breakpoint flanking sequences had no recombination signal sequences (RSSs) or chi sequences and were homologous with the switch region only when the BCL6 gene was fused to the IgH gene, suggesting that BCL6 translocation cannot be explained solely by mistakes of V(D)J, or chi-mediated or class-switch recombination, but rather another mechanism may also be required to explain the molecular mechanism for the promiscuous BCL6 translocation.
Members of the transforming growth factor-beta family play critical roles in body patterning, in both vertebrates and invertebrates. One transforming growth factor-beta-related gene, dbl-1, has been shown to regulate body length and male ray patterning in Caenorhabditis elegans. We screened arrayed cDNAs to identify downstream target genes for the DBL-1 signaling by using differential hybridization. C. elegans cDNAs representing 7,584 independent genes were arrayed on a nylon membrane at high density and hybridized with (33)P-labeled DNA probes synthesized from the mRNAs of wild-type, dbl-1, sma-2, and lon-2 worms. Signals for all the spots representing hybridized DNA were quantified and compared among strains. The screening identified 22 and 2 clones, which were positively and negatively regulated, respectively, by the DBL-1 signal. Northern hybridization confirmed the expression profiles of most of the clones, indicating good reliability of the differential hybridization using arrayed cDNAs. In situ hybridization analysis revealed the spatial and temporal expression patterns of each clone and showed that at least four genes, including the gene for the type I receptor for DBL-1, sma-6, were transcriptionally regulated by the DBL-1 signal.
The Arabidopsis bas1-D mutation suppresses the long hypocotyl phenotype caused by mutations in the photoreceptor phytochrome B (phyB). The adult phenotype of bas1-D phyB-4 double mutants mimics that of brassinosteroid biosynthetic and response mutants. bas1-D phyB-4 has reduced levels of brassinosteroids and accumulates 26-hydroxybrassinolide in feeding experiments. The basis for the mutant phenotype is the enhanced expression of a cytochrome P450 (CYP72B1). bas1-D suppresses a phyB-null allele, but not a phyA-null mutation, and partially suppresses a cryptochrome-null mutation. Seedlings with reduced BAS1 expression are hyperresponsive to brassinosteroids in a light-dependent manner and display reduced sensitivity to light under a variety of conditions. Thus, BAS1 represents one of the control points between multiple photoreceptor systems and brassinosteroid signal transduction.
Mouse monoclonal antibody 13.1 (mAb 13.1) directed against Pbs21, a 21-kDa sexual-stage surface protein of Plasmodium berghei, is known to inhibit oocyst development from gametocytes and ookinetes in the mosquito midgut. To examine the properties and potential uses of a single-chain antibody fragment (scFv) for blocking transmission of malaria parasites to mosquitoes, we have cloned and sequenced the genes encoding variable regions of the immunoglobulin heavy and light chains (V(H) and V(L)) of mAb 13.1. The V(H) and V(L) genes were assembled as an scFv gene, and expressed in a baculovirus expression system. Following purification of 13.1 scFv, Western blotting and inhibition ELISA assays confirmed that 13.1 scFv retained the binding specificity of the parent mAb 13.1 for Pbs21. Furthermore, 13.1 scFv bound to the surface of P. berghei ookinetes, and blocked oocyst development in the mosquito midgut by at least 93%, as assessed by oocyst counts in mosquitoes. We suggest that the 13.1 scFv gene could be useful not only in studying the mechanism of transmission blockade, but also in generating, by mosquito germline transformation, a model system to evaluate the production of mosquitoes refractory to malaria.
Iodine-123-labelled iodoamphetamine single-photon emission computed tomography of patients with reflex sympathetic dystrophy syndrome showed substantial variation in thalamic perfusion of the side contralateral to the painful limb. The variations are related to time from the onset of symptoms, which suggests that the thalamus undergoes adaptive changes in the course of this neurological disorder.
Uncoupling protein 3 (UCP3), expressed abundantly in the skeletal muscle, is one of the carrier proteins dissipating the transmitochondrial electrochemical gradient as heat, and thereby has been implicated in the regulation of energy metabolism. We have investigated UCP3 mRNA expression in the widely used L6 myocyte cell line by Northern blot analysis. UCP3 mRNA was not detected in L6 myoblasts, but appeared after their differentiation to myotubes. The UCP3 mRNA level was increased when L6 myotubes were treated with increasing concentrations of triiodothyronine (T3), oleic acid, alpha-bromopalmitate and carbacyclin, a non-selective ligand of peroxisome proliferator-activated receptors (PPARs), whereas it was not influenced when treated with selective ligands of PPARalpha (WY 14¿ omitted¿643) and PPARgamma (troglitazone). A ligand of retinoid X receptor (RXR), 9-cis retinoic acid, was also effective by itself and in combination with carbacyclin in stimulating UCP3 mRNA expression. The mRNA analysis of individual PPAR isoforms revealed that L6 cell expressed a significant level of PPARdelta but undetectable levels of PPARalpha and PPARgamma. These results suggest that UCP3 expression in myocytes is differentiation-dependent and regulated by the T3 receptor, RXR and PPARdelta.
Vibrio cholerae, a Gram-negative, motile, aquatic bacterium, is the causal agent of the diarrheal disease cholera. Cholera is a serious epidemic disease that has killed millions of people and continues to be a major health problem world-wide. The hypothesis that V. cholerae occupies an ecological niche in the estuarine environment requires that this organism is able to survive the dynamics of physiochemical stresses, including nutrient starvation. As a result of these stresses, bacteria in nature often exist in non-growth or very slow growth states with a low metabolic activity. Because microorganisms have little ability to control their environment, environmental changes have led to changes in cell function and structure. Such cellular responses can originate in one of two ways: by changes in genetic constitution or by phenotypic adaptation. In this review, we will focus on the phenotypic responses of V. cholerae of a given genotype to starvation stress.
BACKGROUND: It remains controversial whether chemotherapy and/or radiotherapy are/is contraindicated for esophageal carcinoma patients with malignant fistulae. In some case reports, closure of fistulae by chemotherapy or radiotherapy has been reported. The current study investigated chemoradiotherapy for these patients using various primary treatments to manage the pulmonary complications. The aim of this study was to evaluate the efficacy and feasibility of chemoradiotherapy for patients with locally advanced esophageal carcinoma with malignant fistulae. METHODS: Patients with endoscopically or radiologically confirmed fistulae were treated with concomitant chemoradiotherapy. Closure of fistulae was assessed by esophagography or endoscopy. Oral food intake also was assessed before and after treatment. RESULTS: Of 202 esophageal carcinoma patients treated at National Cancer Center Hospital East between July 1992 and May 1998, 24 patients (11.9%) developed malignant fistulae. Twelve patients developed fistulae before treatment and the remaining patients developed fistulae during treatment. Closure of the fistulae after chemoradiotherapy was observed in 17 of these patients (70.8%), and 16 of these 17 patients (94.1%) had oral alimentation restored after successful treatment. The median survival time from the diagnosis of the fistula for all patients with fistulae was 198 days; in the patients whose fistulae were present before chemoradiotherapy, the median survival time was 238 days. CONCLUSIONS: These results suggest that the presence of malignant fistulae does not contraindicate chemoradiotherapy. Once the inflammation due to the fistula has been controlled, chemoradiotherapy should be utilized because it may provide the best chance for survival and palliation of severe dysphagia.
BACKGROUND: Various prognostic markers for lung carcinoma have been proposed, but to the authors' knowledge none is noninvasive and convenient for clinical use. The current study examined the utility of several radiotracers for the prediction of multidrug resistance (MDR) and radioresistance in patients with lung carcinoma. METHODS: Thirty patients with untreated lung carcinoma underwent a dual isotope single photon emission computed tomography (SPECT) scan at 10 minutes and 120 minutes after the injection of technetium-99m ((99m)Tc)-tetrofosmin ((99m)Tc-TF) (370 megabecquerels [MBq]) and thallium-201 ((201)TlCl) (111 MBq). Retention of each tracer was evaluated semiquantitatively. Using radiation and chemotherapy (cisplatin plus etoposide), the patients either were treated sequentially (n = 12) or concurrently (n = 18). The relation between therapeutic response and retention of each tracer was analyzed. The detectability of radioresistance was examined. RESULTS: In patients treated with sequential therapy, the response to radiation was predicted by (99m)Tc-TF retention, whereas (201)Tl retention was found not to be predictive. Regardless of whether the sequential or concurrent protocol was applied, 14 of 18 tumors with high (99m)Tc-TF retention (>/= 15%) exhibited a favorable response to chemoradiotherapy whereas all 12 tumors with low (99m)Tc-TF retention (</= 15%) did not respond to the therapy. In contrast, (201)Tl retention was not found to be a predictive factor. CONCLUSIONS: The employed SPECT method is a useful tool for the in vivo prediction of radioresistance, P-glycoprotein (P-gp), and non-P-gp MDR in lung carcinoma. Low (99m)Tc-TF retention serves as a strong predictor of therapeutic resistance. High (99m)Tc-TF retention implies a favorable response. (201)Tl did not appear to be a predictive factor but is required for localization of the lesion on SPECT imaging.
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