Severe ulceration of the stomach after endoscopic injection sclerotherapy.
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Biomedical subjects
Publications and source records attributed to Y Abe.
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OBJECTIVE: The purpose of this study was to analyse changes in regional cerebral blood flow (rCBF) in Parkinson's disease (PD) without dementia. METHODS: Twenty eight non-demented patients with PD and 17 age matched normal subjects underwent single photon emission computed tomography with N-isopropyl-p-[(123)I]iodoamphetamine to measure rCBF. The statistical parametric mapping 96 programme was used for statistical analysis. RESULTS: The PD patients showed significantly reduced rCBF in the bilateral occipital and posterior parietal cortices (p<0.01, corrected for multiple comparison p<0.05), when compared with the control subjects. There was a strong positive correlation between the score of Raven's coloured progressive matrices (RCPM) and the rCBF in the right visual association area (p<0.01, corrected for multiple comparison p<0.05) among the PD patients. CONCLUSIONS: This study showed occipital and posterior parietal hypoperfusion in PD patients without dementia. Furthermore, it was demonstrated that occipital hypoperfusion is likely to underlie impairment of visual cognition according to the RCPM test, which is not related to motor impairment.
We undertook a study of molecular interference of nuclear orphan receptors. Nuclear receptor response element-1 (NRRE-1) from the human medium-chain acyl coenzyme A dehydrogenase (MCAD) gene promoter was shown to contain three hexamer elements (site 1 through 3) that are known to interact with a number of nuclear receptors including chicken ovalbumin upstream promoter transcription factor (COUP-TF) and estrogen-related receptor alpha (ERRalpha). We demonstrated that the peroxisome proliferator-activated receptor alpha/9-cis-retinoic acid receptor alpha (PPARalpha/RXRalpha) heterodimer complex can also bind to the two hexamer repeat sequences (between site 1 and site 3) arranged as an everted imperfect repeat separated by 14 bp (ER14). Mutations of the putative core elements have shown that these three sites are differentially involved in ERRalpha and PPARalpha/RXRalpha binding. Homodimer of ERRalpha was shown to interact between site 1 and site 3 (ER14). To date, no nuclear receptor is known to bind to response elements over such long intervals. Interestingly, site 1 was shown to be essential for ERRalpha binding while site 3 supports its binding only in the presence of site 1. Furthermore, it was shown that the binding profile of ERRalpha and PPARalpha/RXRalpha are competitive rather than making a high order complex within NRRE-1. At the cellular level, transcriptional activation driven by the PPARalpha/RXRalpha complex was counteracted by the expression of ERRalpha in HeLa cells. These results suggest that ERRalpha and PPARalpha/RXRalpha could interfere with each other's function through binding to similar DNA elements, thereby finetuning the transcriptional outcome of the target gene. Our findings suggest a mechanism whereby multiple nuclear receptors can activate or repress DNA binding or transcription via a single pleiotropic regulatory element.
In recent years, experiences with performing off-pump coronary artery bypass (OPCAB) has increased dramatically. Many early reports suggest that this approach may improve outcome by lowering postoperative complications. The benefit of this procedure to elderly patients seems appealing but is not well studied. We sought to review our experience with OPCAB in octogenarians with acute coronary syndrome (ACS) to better define the potential benefit of this approach in this high-risk group of patients. Until March 2003, OPCAB was performed in 21 octogenarians (10 men and 11 women with mean age of 82.9 +/- 2.8 years) with ACS at the department of cardiovascular surgery of National Kanazawa Hospital. Two had myocardial infarction and 3 unstable angina. Mean left ventricular ejection function was 41.2%. 14 patients had a history of previous cerebral infarction. All procedures were completed without hemodynamic deterioration and conversion to on-pump coronary artery bypass grafting (CABG). There was no operative mortality and no occurrence of major complications such as low output syndrome, re-exploration for bleeding, cerebral infarction, perioperative myocardial infarction, and mediastinitis. And no further deterioration of organ function occurred in patients with preexisting central nervous system dysfunction or kidney. Peak CK-MB concentrations after surgery were within normal limits. This study demonstrates that CABG can be performed safely on high-risk ACS patients 80 years of age and older without the use of cardiopulmonary bypass. OPCAB may be the operation of choice for octogenarians with ACS requiring surgical myocardial revascularization.
The mlcR gene encodes a putative 50.2-kDa protein with a Zn(II)(2)Cys(6) DNA-binding domain, which may be involved in the regulation of ML-236B biosynthesis in Penicillium citrinum. The induction of ML-236B production appears to correlate with the expression of mlcR, and the ML-236B biosynthetic genes mlcA- mlcH, and occurs mostly during the stationary phase. The present study was designed to examine the effects of alterations in mlcR expression on ML-236B biosynthesis. We first set out to increase the mlcR copy number in the chromosome of P. citrinum. Transformants with additional copies of native mlcR showed increased transcription of mlcR and produced larger amounts of ML-236B than the parent strain. Altered mlcR expression was also achieved by introducing a construct, designated pgkA(P)::mlcR, that contained the mlcR coding region fused to the (constitutively active) promoter and terminator sequences of the Aspergillus nidulans 3-phospho-glycerate kinase (pgkA) gene. Transformants carrying the pgkA(P)::mlcR construct expressed mlcR constitutively, and produced ML-236B during the exponential growth phase, suggesting that the pgkA(P)::mlcR construct does affect the regulation of ML-236B biosynthesis. Comparative expression analysis by RT-PCR showed that altering the expression profile of mlcR influenced the expression of some of the ML-236B biosynthetic genes. The evidence suggests that mlcR may indeed be involved in the transcriptional activation of some of the pathway-specific genes required for ML-236B biosynthesis.
The gene cluster responsible for ML-236B (compactin) biosynthesis has recently been characterized from P. citrinum No. 41520. Here, we describe how the ML-236B-producing strain was improved using a cosmid-mediated recombination technique. The introduction of the cosmid pML48, which contains seven of the nine ML-236B biosynthetic genes, into P. citrinum No. 41520 resulted in transformants which produced increased amounts of ML-236B. Southern analysis showed that pML48 had been incorporated by a homologous recombination event, and all high producers possessed two copies of each of the seven genes, mlcA- mlcF and mlcR, suggesting that increased dosage of the biosynthetic gene cluster was responsible for the enhanced production of ML-236B. On the other hand, various kinds of mutants with decreased titers of ML-236B were also obtained. Characterization of one such mutant, designated as T48.28, which was more sensitive to ML-236B than the parental strain, suggested that one of the ML-236B biosynthetic genes, mlcD, which encodes a putative HMG-CoA reductase, was involved in conferring resistance to ML-236B.
Cloning of genes encoding polyketide synthases (PKSs) has allowed us to identify a gene cluster for ML-236B biosynthesis in Penicillium citrinum. Like lovastatin, which is produced by Aspergillus terreus, ML-236B (compactin) inhibits the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Genomic sequencing and Northern analysis showed that nine predicted genes for ML-236B biosynthesis were located within a 38-kb region and were transcribed when ML-236B was produced. The predicted amino acid sequences encoded by these nine genes, designated mlcA- mlcH and mlcR, were similar to those encoded by the genes for lovastatin synthesis, and were therefore assumed to be involved either directly or indirectly in ML-236B biosynthesis. Targeted disruption experiments provided evidence that two PKS genes in the cluster, mlcA and mlcB, are required for the biosynthesis of the nonaketide and the diketide moieties, respectively, of ML-236B, suggesting that the gene cluster as a whole is responsible for ML-236B biosynthesis in P. citrinum. Bioconversion of some of the predicted intermediates by an mlcA-disrupted mutant was also investigated in order to analyze the ML-236B biosynthetic pathway. The molecular organization of the gene cluster and proposed functions for the ML-236B biosynthetic genes in P. citrinum are described.
To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma.
OBJECTIVE: The pharmacological effect of vitamin E ointment at high dose levels was investigated in rats and mice during the development of contact dermatitis. MATERIALS AND METHODS: Allergic or irritant contact dermatitis was induced in sensitized or unsensitized animals by topical application of chemical agent(s). Cultured keratinocytes were prepared from dorsal skin of rats. RESULTS: The vitamin E ointment at 20-40% suppressed allergic and irritant contact dermatitis, exerting a comparable effect to that of 0.5% prednisolone ointment. Microscopic findings revealed that 20% vitamin E ointment reduced the keratinocyte damage, whereas 0.5% prednisolone was ineffective. The protective action of vitamin E on keratinocyte damage was also confirmed in a cell culture experiment. Furthermore, 20% vitamin E ointment blocked down-regulation of skin barrier function induced by contact dermatitis, although 0.5% prednisolone ointment was inactive. CONCLUSIONS: These results indicate that 20% vitamin E ointment suppresses contact dermatitis by stabilizing keratinocytes, concomitantly with novel, interesting properties.
We report two cases of patients with malignant lymphoma who presented with early onset of hemophagocytic syndrome after nonmyeloablative allogeneic peripheral blood stem cell transplantation. Fever and skin eruption developed early after transplantation, and neurological symptoms preceded cytopenia and worsened progressively. Activated macrophages with hemophagocytosis were found in bone marrow of the two patients at day 15 and 56, respectively. The fact that no obvious infectious agents associated with hemophagocytic syndrome were detected, and that serum soluble interleukin-2 receptor concentrations were elevated in the early phase after transplantation, reflecting the activation of donor-derived T cells, suggests that this complication resulted from an alloimmune response.
We present a simple compression technique for treatment of difficult nonunions and joint fusions in the hand. This technique utilizes only K-wires and small vessel loops. The results of 44 consecutive cases were studied retrospectively. Union was achieved in 37/44 cases. The average time to union was 7 weeks and our results were comparable to those of other studies. We found this technique useful, especially in complicated cases.
OBJECTIVE: Our long-term results with anterior venous sinus plication (AVSP) for femoral vein reconstruction will be presented. PATIENTS AND METHODS: Between 1986 and 2001 we treated 2 100 patients in our hospital for chronic venous insufficiency. In 3.3 % of the patients (n = 70) an AVSP of the target valve, which is the highest valve of the femoral vein distally of the profundal vein branch was carried out. 50 patients could be followed for 2-15 (average 4.6) years postoperatively by phlebographic control. RESULTS: Four recovery patterns after valve repair were seen on venography. The most typical type was the plicated site stop seen in 22 of 50 patients (44 %). Here the venous reflux was stopped at the plicated site directly. The clinical results were good or excellent for all patients. No patient underwent a second procedure for recurrence of the symptoms. A profundal femoral vein reflux did not negatively influence patient outcome. CONCLUSION: AVSP is an excellent method of valve repair in strictly selected patients with chronic venous insufficiency (= no postthrombotic syndrome, no thrombotic occlusion of the femoral veins). Long-term results up to 15 years were highly satisfactory.
This study examined the ex-vivo occupancy by KMD-3213 of alpha1-adrenoceptors in the prostate and other tissues of rats in terms of tissue selectivity and duration of occupancy in relation to plasma concentration. Oral administration of KMD-3213 (0.2-20.2 micromol kg(-1), 0.5 h) dose-dependently decreased [3H]prazosin binding sites (Bmax) in the prostate (42-74%) and submaxillary gland (54-88%) compared with the control value. In contrast, there was only a slight change in the Bmax values in the spleen and cerebral cortex of KMD-3213-treated rats. The alpha1-adrenoceptor occupancy in the prostate and submaxillary gland was increased, with plasma free concentration of KMD-3213 at 0.5 h after oral administration of KMD-3213 (0.6-20.2 micromol kg(-1)). The receptor occupancy in these tissues was much greater than that in the spleen, heart or cerebral cortex. After oral administration of KMD-3213 (6.1 micromol kg(-1)), the alpha1-adrenoceptor occupancy in the prostate and submaxillary gland occurred rapidly, in parallel with the rise in the plasma concentration of the drug, and it lasted for at least 24 h, despite a remarkable decrease in the plasma concentration. It is concluded that KMD-3213 may produce fairly selective and sustained occupancy of alpha1-adrenoceptors in the prostate, a target organ for treatment of bladder outlet obstruction in patients with benign prostatic hyperplasia.
Recently, off-pump coronary artery bypass grafting (OPCAB) has been rediscovered and spread to avoid the deleterious effect of cardiopulmonary bypass. In OPCAB, surgical exposure of Cx grafting site often threats the hemodynamic stability. We retrospectively analysed the 13 patients with acute coronary syndrome due to LMT lesion who underwent emergent OPCAB to accomplish the safe Cx grafting. We assessed the intraoperative hemodynamic changes and early results of OPCAB through the use of new devices and techniques. Myocardial tissue oxygen saturation was measured by near-infra red spectroscopy during OPCAB. All procedures were completed without hemodynamic deterioration and conversion to cardiopulmonary bypass. No hospital deaths or complications were noted. The early patency rate was 100 percent and perioperative maximal CK-MB was 16.6 +/- 4.7 IU/l. Concomitant use of ischemic preconditioning and KATP opener, oxidative radical scavenger, PD III inhibitor, ameliorated ischemic cardiac dysfunction during occlusion of the coronary artery and improved the postischemic functional recovery. These results suggest that intra-operative compound management may decrease the risk of Cx grafting of OPCAB.
Coronary artery bypass grafting for patients with ischemic heart disease and hypothyroidism contains many controversies, and chronic renal failure causes perioperative water-electrolyte balance disorders. We experienced a case of unstable angina pectoris combined with hypothyroidism and chronic renal failure successfully treated by off-pump coronary artery bypass grafting (OPCAB). A 68-year-old man with a history of hypothyroidism and chronic renal failure was hospitalized with chest pain. Cardiac catheterisation revealed a 90% stenosis of segment 3, 11 and right ventricular (RV) branch, 75% stenosis of segment 6 and 50% stenosis of segment 5. His thyroid function was normal with orally administered levothyroxine. OPCAB was performed safely with hemodialysis until a day before operation and hemofiltration from a day after operation, and postoperative course was uneventful.
Pleomorphic adenoma arising from right middle lobe bronchus is reported in an 18-year-old female. Right middle lobectomy was performed and the histologic pattern of the resected tumor was indistinguishable from that commonly described for pleomorphic adenoma of the salivary glands. Mitotic figures were not present. There has been no recurrence two years following surgery.
Leukemia, a form of haematological malignancy, is a multi-stage disease and a wide range of diverse genes has been speculated to correlate with its initiation and development. Ras has been speculated to be an initiating gene for haematological malignancy, but more investigation will be needed to determine the genes associated with the progression of the disease. 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat leukemia provides a good tool for research into various stages of the disease. The entire coding regions of p53 and ras genes were examined for mutations in the present study. In this experiment, we used fluorescence-labeled polymerase chain reaction single-stranded conformation polymorphism analysis (PCR-SSCP) and direct sequencing to detect mutations of both genes on rat erythroleukemia. Fifteen out of 18 (83.3%) rat leukemias were found to have N-ras codon 61 mutation, consistent with previous results. The result of direct sequencing showed a single base substitution (CAA to CTA), resulting in an amino-acid change from Gln to Leu. No mutations were found in H-ras, K-ras or codon 12 of N-ras. The incidence of p53 gene mutation was 16.6% (3/18) in rat leukemia at late-stage. In the present study, mutation of the p53 gene was detected in three DMBA-induced leukemias as follows: a single-base substitution (CAT to CGT) at codon 177 (exon 5), resulting in an amino-acid change from Arg to Leu, a CGG to CTG/CGG changed at codon 211 (exon 6) resulting in an amino-acid change from His to Arg/His, and a GGG to TGG at codon 242 (exon 6) resulting in an amino-acid change from Gly to Trp, respectively. Thus, mutations of p53 gene do not seem to respond to the carcinogenesis of the DMBA-induced leukemia, in contrast to mutation of the N-ras oncogene, and may possibly be involved in the progress of multi-stage leukemogenesis.