[A case of pancreatic ascites due to rupture of pancreatic pseudocyst successfully treated with continuous arterial infusion of nafamostat mesilate].
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Publications and source records attributed to K Murase.
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To assess the usefulness of enzyme inhibition assay for the diagnosis of primary biliary cirrhosis (PBC), we determined the serial changes in enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) in patients with PBC, and compared the results to those of immunofluorescence and immunoblotting. Forty-nine sera from 19 patients with PBC who were followed-up for at least 16 months were tested for antimitochondrial antibodies (AMA) by indirect immunofluorescence, immunoblotting on bovine heart mitochondria, and enzyme inhibition assay using commercially available TRACE Enzymatic Mitochondrial Antibody (M2) Assay (EMA) kit. Of the 49 sera, 39 (80%), 35 (71%), 38 (78%), 31 (63%), and 36 (73%) were positive for AMA by immunofluorescence, for immunoglobulin G (IgG), IgM, and IgA class antibody against E2 subunit of PDC (PDC-E2) by immunoblotting, and for enzymatic inhibitory antibody to PDC by EMA, respectively. AMA titers determined by immunofluorescence did not change in 9 patients (47%), increased in 4 (21%), decreased in 3 (16%), and fluctuated in 3 (16%) during follow-up. The number of anti-M2 bands by immunoblotting did not change in 9 (47%), increased in 6 (32%), decreased in 2 (11%), and fluctuated in 2 (11%). Units of PDC activity by EMA did not change markedly in 16 (84%), increased in 2 (11%), and fluctuated in 1 (5%). Positive EMA results were common in cases with high levels of serum alkaline phosphatase and IgM, and the units of PDC activity by EMA correlated significantly and inversely with AMA titers by immunofluorescence, and serum reactivity to PDC-E2 by immunoblotting, respectively. There was no correlation between serial changes in biochemical data and units of PDC activity by EMA. In three patients who showed a decrease in AMA titers, AMA titers correlated more with EMA results than immunoblotting. Moreover, in a patient with fluctuating AMA titers, the units of PDC activity by EMA paralleled AMA titers. Our results suggest that EMA is useful for the diagnosis of AMA-positive PBC, and also could be used for monitoring the disease course in PBC.
We investigated the accuracy of a double-injection method for sequentially measuring cerebral blood flow (CBF) with N-isopropyl-(123I)p-iodoamphetamine (IMP) in simulation studies based on patient data and in clinical studies. The unidirectional clearance of IMP from the blood to the brain (K1; nearly equal to CBF) in the first and second sessions was calculated by means of a microsphere model. The K1 values in the first session (K1I) were calculated from Cb(5)/Int_CaI, where Cb(5) and Int_CaI are values for brain radioactivity 5 min after the first injection and for arterial blood radioactivity obtained by 5-min continuous sampling. The K1 values in the second session (K1II) were calculated by means of the following four methods. Method 1: [Cb(tz + 5) - Cb(tz)]/[Int_CaII - Ca(tz) x 5], where Cb(tz+5) and Cb(tz) are the brain radioactivity levels 5 min after the second injection and at the time the second session was started (tz), respectively. Int_CaII and Ca(tz) are the arterial blood radioactivity levels obtained by 5-min continuous sampling after the second injection and at tz, respectively. Method 2: [Cb(tz + 5) - Cb(tz)]/[Int_CaI x R], where R is the injection dose ratio. Method 3: [Cb(tz + 5) - Cb(tz) x exp(- K1I x 5/lambda)]/Int_CaII, where lambda is the population averaged partition coefficient. Method 4: same as Method 3 except that K1I was replaced by K1II obtained by means of Method 2. Theoretically, Method 4 appeared to be the best of the four methods. The change in K1 during the second session obtained by Method 1 or 2 largely depended on R and tz, whereas Method 3 or 4 yielded a more reliable estimate than Method 1 or 2, without largely depending on R and tz. Since Method 2 was somewhat superior to other methods in terms of noninvasiveness and simplicity, it also had the potential for routine clinical use. The reproducibility of two sequential measurements of K1 was investigated with clinical data obtained without any intervention. The response of CBF to acetazolamide challenge was also assessed by the above four methods. The knowledge gained by this study may assist in selecting a method for sequentially measuring CBF with a double injection of IMP.
Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid galactosyl human serum albumin (99mTc-GSA) was performed on 102 patients, then the hepatic extraction fraction (HEF), the rate constant for liver uptake of the tracer from the blood (K1) and the hepatic blood flow index (HBFI) were determined by spectral analysis. The HEF, K1 and HBFI values correlated moderately or closely with various indices of hepatic function, and the HEF and K1 values decreased according to the stage of liver dysfunction. The HEF and K1 values linearly and nonlinearly correlated with HH15 and LHL15, respectively. The HEF, K1 and HBFI values for the irradiated portion of 20 patients before and alter irradiation were compared. The HEF value in patients with a cirrhotic liver significantly (p < 0.002) decreased compared with that in patients with a normal liver at a dose of less than 40 Gy, whereas the HBFI value in patients with a normal liver significantly (p < 0.05) decreased compared with that in patients with a cirrhotic liver at a dose of 40 Gy or greater. This method appears to be a simple, non-invasive and useful tool with which to quantitatively evaluate liver function and it also helps clarify changes in regional function of the irradiated liver.
We analyzed the relationship between regional severity of emphysema, which was evaluated by three-dimensional fractal analysis (3D-FA) of Technegas SPECT images, and coronary heart disease (CHD). For 22 patients with emphysema who underwent Technegas SPECT, we followed up CHD events. The follow-up period was 5.4+/-0.5 (mean +/- SD) years. We defined the upper-lung fractal dimension (U-FD) and lower-lung fractal dimension (L-FD) obtained with 3D-FA of Technegas SPECT images as the regional severity of emphysema. FD became greater with the progression of emphysematous change. During the follow-up period, CHD events occurred in 6 (27%) of the 22 patients. The ratio of U-FD to L-FD for patients with CHD events (0.87+/-0.22) was significantly smaller than for patients without CHD events (1.52+/-0.38) (p = 0.0015). These findings suggest that severer emphysema in the lower lung indicates a higher risk of CHD than that in the upper lung.
Idiopathic retroperitoneal fibrosis (IRF) and primary biliary cirrhosis (PBC) are distinct clinical disorders which rarely occur in the same patient. We report a 79-year-old man with the coexistence of both conditions. The patient had antibodies to both centromere and mitochondria, as indicated by indirect immunofluorescence. Diagnoses of IRF and PBC were confirmed histologically. Although the association between IRF and PBC is obscure, IRF may be involved in many autoimmune diseases associated with PBC.
An accumulation of recent evidence suggests that the mechanism in ischemic preconditioning (IPC) may involve the activation of protein kinase C (PKC) regulatory pathway. In this study, we examined whether the content of 1,2-diacylglycerol (1,2-DAG) and ceramide, which are intracellular second messengers regulating PKC activity, change during IPC in isolated perfused rat hearts, and whether the observed change in 1,2-DAG is accompanied with alteration in its fatty acid composition. Hearts subjected to IPC, consisting of 5-min transient global ischemia followed by 5-min reperfusion, presented a significant functional recovery during subsequent 40-min reperfusion following 40-min global ischemia compared with non-preconditioned hearts. An increase in 1,2-DAG content was observed in hearts subjected to 5-min transient ischemia compared with non-ischemic control hearts, however this was not seen in hearts harvested after 5-min reperfusion following 5-min ischemia. While fatty acid composition in 1,2-DAG was virtually unchanged in hearts subjected to 5-min ischemia, saturated 1,2-DAG decreased and monounsaturated/polyunsaturated 1,2-DAG increased in hearts reperfused for 5-min following 5-min ischemia compared with the non-ischemic control hearts. Ceramide mass did not change significantly, suggesting that the contribution of ceramide may be small in IPC. These data are in concert with the hypothesis that 1,2-DAG is a second messenger in IPC and the changes in fatty acid composition of 1,2-DAG may add new insight concerning signal transduction pathway in IPC.
During postischemic reperfusion, free radicals are produced and have deleterious effects in isolated rat hearts. We investigated whether melatonin (MEL) reduces the production of hydroxyl radical (*OH) in the effluent and aids in recovery of left ventricular (LV) function. Hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. Salicylic acid (SAL) was used as the probe for *OH, and its derivatives 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were quantified using HPLC. In addition, thiobarbituric acid reactive substances (TBARS) in the myocardium was measured. Plateaus in the measurement of 2,5- and 2,3-DHBA were seen from 3 to 8 min after reperfusion in each group. The group that received 100 microM MEL+ SAL had significantly reduced amounts of 2,5- and 2,3-DHBA by multiple folds, compared to the SAL group. TBARS was significantly decreased in the 100 microM MEL group (1.20+/-0.36 vs 1.85+/-0.10 micromol/g of drug-free group, p<0.001). More importantly, the 100 microM MEL group significantly recovered in LV function (LV developed pressure, +dp/dt, and -dp/dt; 63.0%, 60.3%, and 59.4% in the 100 microM MEL group; 30.2%, 29.7%, and 31.5% in the drug-free group, respectively; p<0.05). Duration of ventricular tachycardia or ventricular fibrillation significantly decreased in the 100 microM MEL group (100 microM MEL, 159+/-67 sec; drug-free, 1244+/-233 sec; p<0.05). As a result of scavenging *OH and reducing the extent of lipid peroxidation, MEL is an effective agent for protection against postischemic reperfusion injury.
OBJECTIVE: The objective of this study was to evaluate load transmission in the cancellous bone of the tibia under static and impact load.BACKGROUND. Abnormal transmission of loads may result in osteoarthritis and fractures. However, the role of the cancellous bone in these processes is not well understood.METHODS. The compressive stresses in the subchondral bone, epiphysis and diaphysis of the tibia of porcine knees were measured under static and impact load using mini-pressure transducers. The tests were performed using a drop-tower type testing machine in neutral, varus and valgus alignments. Tests were repeated after meniscectomy and again after removing the articular cartilage.RESULTS. In the intact knee in all alignments, the highest stress on the medial side was found in the epiphysis, and in the subchondral bone on the lateral side. After meniscectomy, a significant increase was observed in the stress in the subchondral bone on both sides. After the articular cartilage was also removed, the stress in the subchondral bone increased again, but slightly.CONCLUSION. The importance of the meniscus in load transmission is supported by this study. The contribution of the articular cartilage to load transmission is less than that of the meniscus.Relevance. The patterns of static and dynamic load transmission observed in this study correlate with the sites of insufficiency fractures of the medial tibial plateau and traumatic lateral tibial plateau fractures observed clinically. Examination of the load transmission is key to a more complete understanding of the causes of osteoarthritis and tibial plateau fractures.
Staphylococcus hyicus is considered to be an etiological agent of exudative epidermitis in young pigs, but is frequently isolated from chickens and cows. In the present study, the proteases of 58 S. hyicus isolates from pigs, chickens and cows were examined by skim milk agar plate culture, gelatinolytic zymogram and polymerase chain reaction (PCR). These isolates showed proteolytic activity on skim milk agar plate, but activity differed amongst the isolates. In the gelatinolytic zymogram, one main band was observed in all the porcine, avian and bovine isolates, while one to two other bands were recognized in some isolates. The formation of the main band was inhibited by EDTA, suggesting that this protease is a metalloprotease. When the Shp1 gene, which codes for one the metalloproteases of S. hyicus as reported previously, was examined by PCR, one band arising from an open reading frame (ORF) was detected in all of 58 isolates tested. In addition, upstream nucleotides containing the promoter region of Shp1 gene were amplified and sequenced. From these results, it seems likely that the metalloprotease is common to porcine, avian and bovine isolates of S. hyicus.
We conducted a randomized controlled trial to assess the efficacy of twice-a-day administration of natural interferon beta (IFNbeta) as an induction of IFN therapy for chronic hepatitis C. Seventy-one patients with chronic hepatitis C were enrolled into the trial and randomly assigned into three treatment groups. Six million units (MU) of IFNbeta were administered once-a-day for the first 4 weeks, and then thrice weekly for 12 weeks in 20 patients (once-a-day group). Three milion units of IFNbeta were administered twice-a-day for the first 2 weeks, 6 MU once-a-day for the next 2 weeks, and then thrice weekly for 12 weeks in 23 patients (twice-a-day+beta group), or 6 MU of lymphoblastoid IFNalpha were administered thrice weekly for the last 12 weeks instead of IFNbeta in 28 patients (twice-a-day+alpha group). Four patients in once-a-day group (20%), 9 in twice-a-day+beta group (39%), and 12 in twice-a-day+alpha group (43%) obtained sustained response. Sustained response rate in twice-a-day groups was higher than in once-a-day group, although there was no statistical significance. The present study suggested the possible superiority of twice-a-day administration of IFNbeta as an induction therapy to once-a-day administration, but further studies are needed to confirm this regimen.
A gene from Vibrio alginolyticus H-8, encoding chitinase, designated as chitinase B, was cloned by the shot-gun method using pUC118 and sequenced. The open reading frame consisted of 846 amino acids including a signal peptide. The molecular mass of the enzyme estimated based on the amino acid sequence data was 90 kDa. The N-terminal amino acid sequence of the enzyme was different from that of chitinase C1 which we had previously reported. This cloned chitinase B was considered one out of four chitinases (A, B, D, and E) which had been newly isolated from the culture broth and cell extract of V. alginolyticus H-8. The gene contained a chitin-binding domain and typical conserved regions of chitinases reported previously. The deduced amino acid sequence of the cloned chitinase B showed high sequence homology with the chitinase from V. parahaemolyticus (84% identity) and the chitinase from V. anguillarum (76.6%), but low sequence homology with the chitinase from V. harveyi (24.4%), and the chitodextrinase from V. furnissii (23.9%). Chitinase E found in cell extract is considered an intracellular chitinase which is different from chitodextrinases.
A gene encoding deacetylase DA1 that is specific for N, N'-diacetylchitobiose was cloned using the shot-gun method with pUC118 and sequenced. The open reading frame encoded a protein of 427 amino acids including the signal peptide. The molecular mass of the mature enzyme estimated from the amino acid sequence data was 44.7 kDa, which is approximately similar to that, estimated by SDS-PAGE (48.0 kDa), of the purified enzyme reported previously. The N-terminal amino acid sequence deduced from the cloned deacetylase gene showed partial sequence homology with the Nod B protein from Rhizobium sp. (37% identity) and chitin deacetylase from Mucor rouxii (28%). It contained a domain, which showed homology with a chitin-binding domain of chitinase A from Bacillus circulans (39%).
We designed four cyclic peptides which are mimics of the C-terminal region of human neuropeptide Y (NPY) on the basis of the structural model of NPY. One of these cyclic peptides, c[D-Cys29-L-Cys34]NPY Ac-29-36 (YM-42454), exhibited significantly higher affinity for the Y1-receptor than the corresponding C-terminal linear fragment, NPY Ac-28-36. Interestingly, YM-42454 showed binding affinity for the Y1-receptor in spite of the lack of the N-terminal sequence of NPY, whereas it did not show any binding affinity for the Y2-receptor. This conformationally restricted Y1-selective peptide would provide some insights into the bioactive conformation of the C-terminal region of NPY.
1. It is well known that extracellular ATP (ATP(o)) elevates the intracellular Ca(2+) concentration ([Ca(2+)](i)) by inducing Ca(2+) influx or mobilizing Ca(2+) from internal stores via activation of purinoceptors in the plasma membrane. This study shows that ATP(o) also activates the plasma membrane Ca(2+) pumps (PMCPs) to bring the elevated [Ca(2+)](i) back to the resting level in human embryonic kidney-293 (HEK-293) cells. 2. The duration of ATP(o)-induced intracellular Ca(2+) transients was significantly increased by PMCP blockers, La(3+) or orthovanadate. In contrast, replacement of extracellular Na(+) with NMDG(+), a membrane-impermeable cation, had no significant effect on duration, thus suggesting that Na(+)/Ca(2+) exchangers do not participate in the ATP(o)-induced Ca(2+) transient. 3. A rapid and significant decrease in [Ca(2+)](i), which was not dependent on extracellular Na(+), was induced by ATP(o) in cells pretreated with thapsigargin (TG). This decrease was blocked by orthovanadate, indicating that it was caused by PMCPs rather than sarco/endoplasmic reticulum Ca(2+) pumps (SERCPs). 4. UTP and ATPgammaS also caused a decrease in [Ca(2+)](i) in cells pretreated with TG, although they were less effective than ATP. The effect of UTP implies the involvement of both P2Y(1) and P2Y(2) receptors, while the effect of ATPgammaS implies no significant role of ectophosphorylation and agonist hydrolysis in the agonist-induced [Ca(2+)](i) decreases. 5. These results point to a role of PMCPs in shaping the Ca(2+) signal and in restoring the resting [Ca(2+)](i) level to maintain intracellular Ca(2+) homeostasis after agonist stimulation.
AIM: To determine whether a 5-day regimen with rabeprazole, clarithromycin and amoxicillin (RCA) was as effective as a 7-day regimen. METHODS: A total of 139 H. pylori-infected patients were randomized to receive either a 5-day or 7-day course of rabeprazole 10 mg b.d., clarithromycin 400 mg b.d. and amoxicillin 750 mg b.d. Eradication was assessed by CLO test, histology and 13C-urea breath test. RESULTS: On the intention-to-treat basis, eradication rates were 66% (46 out of 70) and 84% (58 out of 69) for the 5- and 7-day regimens, respectively (P < 0.05). Using per protocol analysis, eradication rates were 70% (46 out of 66) and 91% (58 out of 64) for the 5- and 7-day regimens, respectively (P < 0.01). Adverse events, which were observed in 14 patients from each group, caused discontinuation of treatment in only two patients, resulting in excellent compliance. CONCLUSIONS: Our 5-day regimen of RCA yielded inferior results, whereas the 7-day regimen achieved an eradication rate exceeding 90% on the per protocol basis. Therefore, treatment regimens of less than 7 days for proton pump inhibitor-clarithromycin-amoxicillin therapies cannot be recommended.
Most cases of cholangiocarcinoma have reached an unresectable stage by the time they are discovered despite significant progress of diagnostic modalities. Many of these patients with obstructive jaundice are often treated by biliary drainage using stents to relieve the jaundice. However, the stent patency period is as short as 3 to 9 months because of tumor ingrowth or overgrowth, and mean survival is at most 12 months. Therefore, both continuous relief of obstructive jaundice and local control of the tumor are required in the treatment for advanced cholangiocarcinoma. In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT). CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro. When CCT was embedded in subcutaneous tumor inoculated in nude mice, a significant reduction of tumor size with no apparent damage to normal adjacent tissue was observed. On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks. Overall efficacy rate of 5 patients with cholangiocarcinoma was 60% (partial response in 3 and no change in 2). No apparent side effect was observed in these patients. Thus, CCT may provide a new treatment modality for this disease. Randomized controlled trials comparing CCT therapy with palliative stenting are required to confirm these results.