Involvement of Porphyromonas gingivalis in the progression of non-alcoholic fatty liver disease

Journal of Gastroenterology - The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be...     

Atpenins,potent and specific inhibitors of mitochondrial complex II (succinate-ubiquinone oxidoreductase)

Enzymes in the mitochondrial respiratory chain are involved in various physiological events in addition to their essential role in the production of ATP by oxidative phosphorylation. The use of specific and potent inhibitors of complex I (NADH-ubiquinone reductase) and complex III (ubiquinol-cytochrome c reductase), such as rotenone and antimycin, respectively, has allowed determination of the role of these enzymes in physiological processes. However, unlike complexes I, III, and IV (cytochrome c oxidase), there are few potent and specific inhibitors of complex II (succinate-ubiquinone reductase) that have been described. In this article, we report that atpenins potently and specifically inhibit the succinate-ubiquinone reductase activity of mitochondrial complex II. Therefore, atpenins may be useful tools for clarifying the biochemical and structural properties of complex II, as well as for determining its physiological roles in mammalian tissues.     

Frequent loss of heterozygosity on chromosome 10p14-p15 in esophageal dysplasia and squamous cell carcinoma

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including glioma, pulmonary carcinoid and cervical, hepatic and prostatic carcinomas. These findings suggest the presence of a tumor suppressor gene at the loci. However, analysis of LOH on chromosome 10p14-p15 in esophageal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 88 esophageal squamous cell carcinomas (SCC) (35 superficial- and 53 advanced-types) and 44 dysplasias by microsatellite assay. Five oligonucleotide primer sets for microsatellite loci D10S191, D10S501, D10S559, D10S558 and D10S249 were used. In dysplasias, frequent LOH was detected with markers D10S191 (26%) and D10S249 (33%). In superficial esophageal SCCs, frequent LOH was detected with markers D10S191 (26%), D10S559 (50%), D10S558 (29%) and D10S249 (33%). In advanced esophageal SCCs, we found frequent LOH was detected with markers D10S191 (38%), D10S501 (25%) and D10S559 (30%). There were no significant correlations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion and lymph node metastasis. These data suggest that a putative tumor suppressor gene for esophageal carcinogenesis may be located on chromosome 10p14-p15 and that malfunction of this gene may be involved in the development but not progression of esophageal tumors.     

Two case reports of complete regression of liver metastases from colorectal cancer after locoregional immunochemotherapy

Hepatic arterial infusion (HAI) with pharmacokinetic modulating chemotherapy (PMC) has been well known to be one of the most effective protocols for unresectable liver metastases from colorectal cancer. PMC is a combination of oral UFT and continuous hepatic arterial 5-FU infusion. We present herein the cases of two patients with multiple liver metastases from colorectal cancer in whom complete regression (CR) was achieved by HAI with PMC in combination with Lentinan (immunostimulator). These patients received HAI via an implantable port system with a 4-24-hour continuous perfusion of 5-FU at 1,000 mg/m2 plus Lentinan at 2 mg/body once a week, and oral administration of UFT at 200-300 mg/m2/day everyday. CR of all metastatic lesions in the liver was achieved 4 months after the initiation of the treatment in both patients. One patient maintained CR for 3 months, but he died due to a recurrence of liver metastases and peritoneal dissemination 19 months after the initiation of the treatment. The other patient has been well without recurrence for 21 months. Because the liver is the largest immunologic organ, Lentinan could have activated lymphocytes and macrophages in the liver. Judging from the clinical experience of these two cases, HAI with PMC in combination with Lentinan could be one of the most promising treatment strategies for unresectable liver metastases from colorectal cancer.     

Three-dimensional computed tomography in the head and neck diseases with bony abnormalities

The purpose of this study was to define the role of three-dimensional (3D) computed tomography (CT) in the head and neck diseases with bony abnormalities. Thirty-two patients were examined with a low dose radiation technique. Three-dimensional CT clearly delineated bony lesions in 27 of 32 patients. Three-dimensional CT could not demonstrate subtle bony erosions infiltrated by tumor, a temporal bone fracture, and a blow-out fracture, although two-dimensional (2D) images obtained before the 3D reconstructions clearly depicted those lesions. These two kinds of CT technique were thought to be complimentary.     

Enhanced fibrinolytic activity during the course of hemodialysis.

In order to clarify the effect of hemodialysis (HD) on the fibrinolytic system, fibrinolytic activity was evaluated in 27 patients undergoing regular hemodialysis treatment (RDT) using new parameters including plasma alpha 2-plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor-1 (PAI-1) antigen. Predialysis baseline levels of plasminogen and alpha 2PI activity in RDT patients were significantly lower and those of alpha 2PIC were significantly higher than normal control values. During a single HD session, alpha 2PIC exhibited a continuous, significant increase reaching about 180% of initial values by the end of HD. alpha 2PI activity was significantly decreased at the end of the HD, though there were no significant changes in plasminogen activity during HD. Predialysis baseline levels of XL-FDP in RDT patients were significantly higher than normal control values. No significant changes in XL-FDP were observed during HD. Both t-PA activity and t-PA antigen significantly increased during HD, and PAI-1 antigen significantly decreased during HD. Von Willebrand factor (vWF) antigen in plasma, which is regarded as reflecting a release reaction by vascular endothelial cells to certain stimuli, also significantly increased during HD. However, neither vWF antigen nor t-PA antigen was increased by heparin administration alone. The changes in alpha 2PI and alpha 2PIC levels suggest that fibrinolytic activity is slightly higher in RDT patients and is even higher during HD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical effects of six-month short time biofiltration]

The clinical effects of six-month short time biofiltration (SBF) were evaluated using a B-A-B' study (B, B': conventional bicarbonate hemodialysis; CBHD, A:SBF) in ten patients maintained on CBHD three times a week. An F80 hemodiafilter (1.9 m2, polysulfone, Fresenius) was used. In addition to routine clinical parameters for a patient on regular dialysis treatment, plasma von Willebrand factor antigen (vWF) (an index of stimulation of vascular endothelium), and the methylguanidine/creatinine ratio (MG/Cr) and malondialdehide (MDA) (indices of the levels of oxygen radicals), were evaluated. Nine patients completed the study, one patient dropping out at the 12th week of A because of muscle cramps during SBF. The treatment time was 2 hours in six cases and 2.5 hours in three cases. The mean blood flow rate was 280 +/- 42 (SD) minutes. Using the urea kinetics model, the mean KT/V was 1.26 +/- 0.28, and the mean protein catabolic rate was 1.22 +/- 0.18 g/kg body weight/day at the end of A. No change in ultrafiltration, blood pressure, cardiac function (assessed by echocardiography), CTR, human atrial natriuretic peptide, total protein, albumin, uric acid, serum creatinine, sodium, calcium, inorganic phosphorus, vWF, or MDA was found between each period. Blood urea nitrogen, c-PTH, and MG/Cr increased during the A period. Serum magnesium and beta-2 microglobulin decreased during the A period. Blood gas results, on the whole, did not change. In a patients, however, acidosis gradually developed. An increase in substitution fluid from 5 L/session to 7.5 L/session improved the acid-base balance in that patient. In conclusion, SBF is as effective as CBHD in removing small molecules and maintaining cardiocirculatory status, and is superior to CBHD in removing beta 2-microglobulin and is less stimulative to the endothelium than CBHD.     

Procainamide-DNA interaction

The interactions of procainamide with DNA were studied by neutral and alkaline sucrose gradient sedimentation and sequential action of 2 enzymes: a mammalian repair endonuclease and bacterial DNA polymerase I. Sucrose gradient sedimentation shows that in the absence of photosensitization, the interaction of procainamide with DNA did not modify DNA sedimentation in alkaline or neutral sucrose gradients. In contrast, when a photosensitized DNA procainamide mixture was placed on sucrose gradients, the peak appearing on alkaline sucrose gradient after treatment with endonuclease was shifted toward the lower molecular weights, indicating that strand breaks had developed in the photosensitized procainamide DNA. Incubation of a [32P] labeled photosensitized procainamide-DNA complex with a repair endonuclease and DNA polymerase I released the label in the acid soluble fraction, indicating that only the photosensitized procainamide-DNA complex was susceptible to the endonucleolytic attack. There was only negligible release of the label in the acid soluble fraction without exposure of the DNA-procainamide mixture to light. The incorporation into DNA of [3H]-TTP (tritium labeled triphosphates) in presence of DNA polymerase I was inhibited when the photosensitized procainamide-DNA complex was used as substrate. However, after treatment of the photosensitized DNA complex with the repair endonuclease, the incorporation of [3H]-TTP was increased and reached values close to that observed with DNA unexposed to light, suggesting that the endonuclease functions as a repair enzyme.