Inhibition of cholesteryl ester transfer protein by fungal metabolites, L681,512.
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Biomedical subjects
Publications and source records attributed to Y Yamaguchi.
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Gliocladium roseum KF-1040, a marine isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Four active compounds, designated roselipins 1A, 1B, 2A and 2B, were isolated from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography and preparative HPLC. The highest production of roselipins was observed when cultured in the medium containing natural sea water. Roselipins inhibit DGAT activity with IC50 values of 15 approximately 22 microM in an enzyme assay system using rat liver microsomes.
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Drug selection for eradication therapy of H. pylori, considering their drug resistance was evaluated. The measurement of resistant colonies was performed in blood agar plates using the MIC method and the criteria for resistance was as follows: MIC > 1 mg/l with AMPC, MIC > 2 mg/l with CAM and MIC > 8 mg/l with MNZ. Primary resistant colonies were found in 0% with AMPC, 8.9% with CAM and 5.9% with MNZ. Secondary resistant colonies were found in 0% with AMPC, 50.0% with CAM and 54.5% with MNZ. CAM and MNZ showed high resistance rate and among them, colonies resistant to CAM were also highly resistant to MNZ. But colonies resistant to MNZ (acquired after CAM) were all sensitive to AMPC. Considering this issue and the absence of resistance to AMPC, we considered the triple therapy with AMPC, MNZ and a PPI as the best option for the eradication of H. pylori.
Of patients radically operated on for breast cancer in our department, 46 patients who had recurrent breast cancer were clinicopathologically evaluated to clarify the prognostic factors of recurrent breast cancer. Furthermore, p53, p21 and cyclin D1 protein expression were studied immunohistochemically and their prognostic value was evaluated. The relapse-free interval was highly related to the survival rate after the recurrence. p53 overexpression was correlated with the progression of clinical stage and lymph node metastasis and negatively correlated with the expression of estrogen receptor. The p21 positive and p53 negative cases had a significantly better prognosis than the p21 negative and p53 positive cases. The combination of p53 and p21 protein expression seemed to have prognostic value in recurrent breast cancer.
Because of the difficulty in obtaining biopsy specimens from pancreatic cancer patients, K-ras mutation analysis in pancreatic juice has been used for specific diagnosis. But recently, false positives have been obtained with this method. To improve the genetic diagnosis of pancreatic cancer, detection of p53 gene mutation in pancreatic juice was studied. Pancreatic juice was sampled endoscopically. Single-strand conformation polymorphism analysis was used for p53 mutation analysis. Furthermore, K-ras mutations at codon 12 were also studied in the same pancreatic cancer patients. Of 26 cases of pancreatic cancer, p53 mutations were detected in 11 (42.3%). No mutations were seen in the cases with mucin-producing adenoma nor with chronic pancreatitis. K-ras mutations were detected in 84.0% of cases by RFLP analysis, which has high sensitivity, and in 65.3% by hybridization protection assay, which has high specificity. Using a combination assay with both genes, genetic abnormalities were detected in 92.0% by RFLP and 73.1% by hybridization protection assay including two cases in which p53 alone was positive by both methods. The specificity of p53 mutation for pancreatic cancer is very high. Therefore, simultaneous analysis of p53 and K-ras mutation is suggested to enhance the genetic diagnosis of pancreatic cancer.
PURPOSE: We evaluate the efficacy of a new technique of minimally invasive treatment for benign prostatic hyperplasia involving direct injection of dehydrated ethanol. MATERIALS AND METHODS: Dehydrated ethanol was injected transurethrally with lumbar or sacral and urethral anesthesia in 10 patients with prostatic hyperplasia. Endoscopic injection was performed at 4 to 8 sites in the prostate and 3.5 to 12.0 ml. ethanol were used. RESULTS: There were no intraoperative complications but postoperative urinary retention occurred transiently in all patients which required catheterization for a mean of 8.8 days. Mean symptom score plus or minus standard deviation was 12.2+/-5.8 at 3 months postoperatively, which was significantly improved from 23.1+/-7.0 preoperatively (p<0.01). Mean quality of life score also improved significantly from 5.1+/-0.6 preoperatively to 3.2+/-1.5 at 3 months postoperatively (p<0.01), mean peak urinary flow rate increased from 8.0+/-2.2 (9 patients) to 13.1+/-3.6 ml. per second (p<0.05) and mean residual urine volume decreased from 129.1+/-55.3 (9 patients) to 49.3+/-34.7 ml. (p<0.05). There was no significant change in prostate volume. Acute epididymitis and chronic prostatitis occurred in 1 patient each. CONCLUSIONS: This technique can be performed as an outpatient procedure and appears to be safe and cost-effective. Retrograde ejaculation can be avoided.
The adherence of activated neutrophils to endothelial cells during ischemia/reperfusion injury is mediated by inside-out signal transduction. Subsequently, outside-in signal transduction occurs following ligation of adhesion molecules with their ligands triggering respiratory bursts of neutrophils. In addition, neutrophil elastase enhances CC- and CXC-chemokine production by monocytes and macrophages. MCP-1, a CC-chemokine, enhances tissue factor production by macrophages and increases ICAM-1 expression on endothelial cells. Chemotaxis and respiratory bursts of neutrophils are augmented by CXC-chemokines. Furthermore, neutrophil elastase inactivates anticoagulants including antithrombin III, heparin cofactor II, and thrombomodulin, suggesting that neutrophil elastase aggravates microcirculatory disturbance after ischemia/reperfusion. Thus neutrophil elastase modulates the interation of neutrophils and endothelial cells during ischemia/reperfusion injury. Taken together with these observations, a therapeutic regimen with antibodies against adhesion molecules in combination with neutrophil elastase inhibitor and anticoagulants may attenuate ischemia/reperfusion injury.
We here report the first case of postmortem injury caused by a centipede. An old man was found dead in his bedroom. The death was estimated to be due to intracranial hemorrhage and to have occurred two days before the police inspection. A centipede about 12 cm long emerged from a subcutaneous cavity on the victim's forearm. Obviously, the centipede had dug the cavity on the intact skin. A police inspector was bitten by the centipede, so he stepped on the centipede on the floor. The exudate from the insect was identified to be derived from the victim's blood.
Proteases influence various leukocyte effector functions. We investigated the specific binding activity of neutrophil elastase (NE) on rat peritoneal macrophages to stimulate chemokine production in vitro. NE enhanced macrophage production of monocyte chemo-attractant protein-1 (MCP-1) (CC-chemokine) and cytokine-induced neutrophil chemo-attractant (CINC) (CXC-chemokine). However, the serine protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), significantly reduced these chemokine productions by macrophages stimulated with NE. 125I-NE was significantly bound to macrophages, but 125I-NE binding was inhibited by addition of unlabeled NE. In addition, NE significantly stimulated [3H]thymidine incorporation into DNA on 3T3 fibroblasts in a dose-dependent manner. These results suggest that NE stimulates chemokine production by macrophages. This may be a receptor-mediated reaction. Thus, NE not only degrades extra-cellular matrix but also stimulates chemokine production by macrophages.
A 20-year-old man presented with microcytic hypochromic anemia (hemoglobin: 9.3 g/dl, MCV: 82.0 fl, MCHC: 29.5 g/dl) and dimorphism RBCs in circulating blood (RDW: 26.8%). Ringed sideroblasts accounted for 29.5% of bone marrow erythroblasts. Iron overload was also observed. Because the patient had a clear family history of anemia, he was given a diagnosis of X-linked sideroblastic anemia. The activity of delta-aminolevulinic acid synthase (ALAS) in bone marrow erythroblasts was low. However, we did not detect mutation of the gene for ALAS. The patient has responded well to a treatment regimen consisting of oral vitamin B6, Fe-chelation therapy, and phlebotomy.
This paper describes BRAVO/TeleTrend--a comprehensive client/server-based system for remote access, review and analyses of continuously acquired multiparametric physiological data from Intensive Care unit (ICU) patients. The system is designed as a distributed three tier model and implemented in Java (Sun Microsystems). TeleTrend is a data review package, which interfaces to existing physiological bedside monitors such as the BRAVO suite of products (Nicolet Biomedical, Madison, WI) and the vital signs monitors compatible with the Unity Network (Marquette Electronics, Milwaukee, WI). It does not transfer over the web the entire patient record, which can be hundreds of megabytes. Instead, it provides tools to view a compressed representation of the raw data in a trend display and to zoom into the raw data if needed. Thus, it eliminates the need for a high-bandwidth Internet connection and makes possible the use of a slower modem access to the vast amount of physiological data acquired per patient. In addition, TeleTrend features a rule-based module capable of generating clinical alerts, which is a potentially useful tool for neurointensivists and other critical care personnel. Finally, TeleTrend is intended as a multi-user, semi real-time telemedical application, which features built-in white-board and chat components. These components allow several physicians at different locations around the world to simultaneously view and brainstorm over critical chunks of continuously recorded raw and trend data. By allowing the end-user user to switch on-the-fly from monitoring patients in one ICU to those in another, and by integrating an HL7 interface TeleTrend steps over the boundaries of a single ICU. Thus, it can be provide a medical enterprise-wide solution to the remote access of an important component of the electronic patient medical record. Currently in house validation, verification and alpha testing of the system are underway.
Dysgeusia was investigated in 11 patients with thalamic infarction and 13 patients with corona radiata infarction to locate the gustatory pathways based on the sites of the lesions. Dysgeusia was present in 4 out of 11 patients with thalamic infarction and 3 out of 13 patients with corona radiata infarction. The dysgeusia was contralateral to the lesion in all these patients. Cheiro-oral syndrome was observed as a complication in 2 patients each from both groups. The responsible lesion was located on the medial side of the ventral posterolateral (VPL) nucleus and the ventral posteromedial (VPM) nucleus in the patients with thalamic infarction who developed dysgeusia, and was located posteriorly to the corona radiata in the other group. In the patients without gustatory disturbance, on the other hand, the lesions showed no such spread. These findings suggest that the gustatory pathway ascends contralaterally in the cerebral hemisphere and that the pathway from the thalamus projects to the cerebral cortex via the posterior part of the corona radiata. It is also suggested that the pathways in the thalamus and corona radiata are very close to the sensory fibers from the mouth and hands projecting to the sensory area.
We experienced a long-term surviving case from excellent control of a multiple metastatic liver tumor from rectal cancer. The patient was a 38-year-old male, and his chief complaint was pain at defecation. The primary lesion was diagnosed as rectal cancer (Rb), and it was histologically found to be well-differentiated adenocarcinoma. The preoperative enhanced CT demonstrated 8 metastatic lesions in bilateral lobes of the liver. Low anterior resection for rectum and open microwave coagulation therapy (MCT) for liver metastasis were synchronously performed. The coagulated areas after MCT revealed no enhancement. The serum CEA levels returned to normal for 9 months. Nine months after the first operation, we detected 6 recurrent lesions in the other sites of the remnant liver. We used second open MCT because the hepatic arterial chemotherapy was ineffective. We performed percutaneous MCT for the next new lesions. The patient was diagnosed with lung metastasis 2 years after the first operation, and died of cancer growth 2 years and 9 months after the first operation. This long-term surviving case of nine metastatic liver tumors achieved adequate quality of life by a combination therapy mainly consisting of MCT.
A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.
Essential thrombocythemia (ET) was diagnosed in a 31-year-old woman who had a miscarriage in the first trimester of her first pregnancy. Because of her wish for child, the patient was given alpha interferon (alpha-IFN) instead of hydroxyurea or aspirin to lower her platelet count to about 80 x 10(4)/microliter. She also had a miscarriage in her second pregnancy. Thereafter, the platelet count was kept at 60-70 x 10(4)/microliter by dose escalation of alpha-IFN. In the 35th week of her third pregnancy, the patient delivered a healthy baby with a normal blood count. Several small infarctions were observed in the placenta. Control of platelet count by alpha-IFN administration was effective in preventing recurrent miscarriage associated with ET, and had no adverse effect on patient fertility or fetal development.
Carbon beam radiation has well-balanced dual actions on cancer: efficient dose localization and potent biological anticancer effect due to high RBE (Relative Biological Effectiveness). Two phase I/II clinical studies on the carbon beam radiation treatment of inoperable stage I non-small cell lung cancer (NSCLC) were carried out in our institution from October 1996 to February 1999. The dose-limiting toxicity was found to be radiation pneumonia. In the first protocol, 47 patients received 18 fractions of increasing doses from 59.4 GyE by 10% over 6 weeks. The maximum tolerated dose was found to be 95.4 GyE, while the complete tumor control dose was 85.6 GyE. In the second protocol, 34 patients received 9 fractions of in creasing doses from 68.4 GyE by 5% over 3 weeks. The maximum tolerated dose was 79.2 GyE, and the complete tumor control dose was > 68.9 GyE. The 4-year survival rate estimated by the Kaplan-Meier method was 56% for patients receiving the first protocol. Because a higher local control rate was achieved in the second protocol, the 5-year survival rate is estimated to be higher and similar to that achieved after surgery. Another phase II clinical study in patients with stage INSCLC is ongoing. Heavy-particle radiotherapy is a new modality for the treatment of lung cancer which holds promise for the 21st century.