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Biomedical subjects

T Kaji

Publications and source records attributed to T Kaji.

At least 37 records · Page 2Linked to original sources

Modulation of collagen synthesis by tumor necrosis factor alpha in cultured vascular smooth muscle cells.

Collagen synthesis in vascular smooth muscle cells (SMCs) after exposure to tumor necrosis factor alpha (TNF-alpha) was investigated using a culture system. The synthesis of collagenase-digestible proteins (CDP) and noncollagenous proteins (NCP) was evaluated by the [3H]proline incorporation. It was shown that TNF-alpha markedly suppresses the incorporation of [3H]proline into both CDP and NCP in confluent cultures of SMCs but not in sparse cultures of the cells. Such a marked suppression by TNF-alpha was not observed in confluent bovine aortic endothelial cells and human fibroblastic IMR-90 cells. In confluent SMCs, the synthesis of CDP was more strongly inhibited by TNF-alpha than that of NCP. When the CDP synthesis was stimulated by transforming growth factor beta, TNF-alpha suppressed the stimulation in both confluent and sparse SMCs. Human SMCs synthesized types I, III, IV and V collagens; TNF-alpha markedly decreased the relative proportion of types IV and V. It was therefore suggested that TNF-alpha modulates the collagen synthesis by SMCs depending on their cell density and modifies the formation of atherosclerotic lesions.

Animals↗

Diagnostic accuracy of a new non-invasive enzyme immunoassay for detecting Helicobacter pylori in stools after eradication therapy.

BACKGROUND: Helicobacter pylori eradication therapy has been commonly performed for patients with peptic ulcer. An inexpensive, reliable, non-invasive test would be useful for evaluation of the effectiveness of eradication therapy. AIM: To evaluate the diagnostic potential of a new non-invasive enzyme immunoassay (HpSA) for H. pylori antigen in stools. METHODS: A total of 112 peptic ulcer patients with H. pylori infection (82 male, 30 female; age range 22-81 years, mean 54 years) received a course of eradication therapy. Four weeks after the end of the therapy, stool samples were collected from all patients and tested using the HpSA. The diagnostic accuracy of the HpSA EIA was evaluated in comparison with the results of a 13C-urea breath test. RESULTS: The diagnostic sensitivity of HpSA EIA after eradication therapy was 90%, the specificity 98%, the positive predictive value 82% and the negative predictive value 99%. CONCLUSION: The HpSA stool test is potentially useful for the diagnosis of H. pylori infection 4 weeks after the end of eradication therapy.

Adult↗

Efficacy of sucralfate for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen.

BACKGROUND: Sucralfate has an inhibitory action against Helicobacter pylori and enhances the anti-H. pylori activity of antimicrobials. AIM: To evaluate the efficacy and safety of sucralfate-based eradication therapy for H. pylori infection, compared with that based on lansoprazole, in a randomized multicentre study. SUBJECTS AND METHODS: The subjects were 150 H. pylori-positive patients. They were randomly assigned to one of two regimens for 2 weeks: sucralfate 1 g t.d.s., amoxycillin 500 mg t.d.s., and clarithromycin 400 mg b.d. (SAC regimen: 75 patients); or lansoprazole 30 mg o.m. with the same antimicrobial medications (LAC regimen: 75 patients). Cure of infection was assessed by a 13C urea breath test 1 month after completion of treatment. RESULTS: Eight patients (four in the SAC group and four in LAC group) could not continue therapy because of severe diarrhoea, and three did not take the 13C urea breath test after therapy. Cure rates for intention-to-treat, all-patients-treated, and per protocol analysis in the SAC group were 80%, 83%, and 88%, respectively, and those in the LAC group were 87%, 87%, and 92%, respectively. There were no significant differences in cure rate or adverse effects between the two regimens. CONCLUSION: Sucralfate in combination with amoxycillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Hard-copy versus soft-copy with and without simple image manipulation for detection of pulmonary nodules and masses.

PURPOSE: To compare interpretation performance on soft-copy presentations, with and without simple image manipulation, and on unmodified hard-copy presentations with regard to detection of pulmonary nodules and masses. MATERIAL AND METHODS: Fifty chest digital radiograph combinations of patients with a total of 60 nodules, 32 of which were 2.0 cm in diameter, were selected for the study. Three readers evaluated three separate image formats: unmodified hard- and soft-copies, and soft-copies with simple image manipulation of lung and mediastinum window settings, and zooming. The screen display was 1600 x 1200 pixels with 8 bits/pixel. RESULTS: The sensitivity, accuracy, detectability, and Az value of the soft-copy systems were clearly inferior to hard-copy evaluation. The mean Az values were 0.921 for unmodified hard-copy, 0.820 for image-manipulated soft-copy, and 0.781 for unmodified soft-copy. CONCLUSION: Soft-copy interpretations were not as sensitive in detecting pulmonary nodules and masses as hard-copy evaluation.

Adult↗

Clinical pharmacokinetics and effects of an oral sustained-release preparation of disopyramide prescribed for patients undergoing maintenance hemodialysis.

AIMS: We evaluated the clinical pharmacokinetics of a sustained-release preparation of disopyramide phosphate (DSR) and its effects on supraventricular arrhythmias in hemodialysis patients. METHODS: Eight hemodialysis patients with either paroxysmal supraventricular tachycardia (PSVT) or PSVT plus paroxysmal atrial fibrillation (Paf) were given 150 mg of DSR 2 h before each hemodialysis. The frequency of PSVT, the duration of Paf before and 2 weeks after starting DSR and the blood concentration of the drug were evaluated. RESULTS: There was no significant difference between serum levels of DSR before and after hemodialysis. The frequency of PSVT and the duration of Paf were significantly reduced by the therapy. Side effects and electrocardiographic abnormalities did not appear during the period. CONCLUSION: We conclude that hemodialysis does not remove DSR, and that a single dose of 150 mg of DSR given 2 h before hemodialysis is safe and sufficient to reduce the incidence of supraventricular arrhythmias.

Administration, Oral↗

Prevalence and clinical characteristics of patients with atrial fibrillation: analysis of 20,000 cases in Japan.

In Japan, data on the epidemiological and clinical features of atrial fibrillation (AF) are rather sparse; even less data are available on the risk of thromboembolism in nonvalvular AF. The present study enrolled 19,825 patients who visited the cardiovascular clinics of the 13 hospitals in Hokkaido, Japan, between March and July 1995. The prevalence of AF, the clinical characteristics of AF patients, and the occurrence of ischemic events were examined during the 2 year follow-up period. The prevalence of AF increased with age, and the overall prevalence was 14%. Antithrombotic therapy was used in 57% of AF patients and the incidence of ischemic events during the follow-up period was 4.6% in all AF patients. Warfarin reduced the risk of ischemic events in both the valvular and nonvalvular AF groups. A history of cerebrovascular accidents, advanced age, and the presence of underlying heart disease were each associated with a significantly increased risk of ischemic events in the nonvalvular AF group. These results show a lower incidence of ischemic events and more frequent use of antiplatelet drugs in the nonvalvular AF group. Further prospective studies are needed to determine the best preventive methods for thromboembolic complications in Japanese patients with nonvalvular AF.

Adult↗

Possible mechanism for lead inhibition of vascular endothelial cell proliferation: a lower response to basic fibroblast growth factor through inhibition of heparan sulfate synthesis.

Although lead inhibits the proliferation of vascular endothelial cells, the mechanism has been incompletely understood. A lower response to basic fibroblast growth factor (bFGF) of growing bovine aortic endothelial cells after exposure to lead was investigated using a cell culture system in the present study. It was shown that lead significantly decreased the incorporation of [3H]thymidine into the acid-insoluble fraction of the cells but the inhibition disappeared in the presence of bFGF neutralizing antibody. Pretreatment with lead resulted in a reduction of the stimulation by exogenous bFGF on the [3H]thymidine incorporation. Lead decreased endogenous bFGF bound to cell surface heparan sulfate proteoglycans in a concentration-dependent manner but not the high affinity FGF receptor without a change of the accumulation within the cells. In spite of such a change in the endogenous bFGF distribution, the total amount of the growth factor synthesized was not significantly changed by lead. Although the binding of [125I]bFGF to heparan sulfate proteoglycans can be directly inhibited by lead, the inhibition was not so marked. On the other hand, lead markedly suppressed the incorporation of [35S]sulfate into heparan sulfate accumulated in the cell layer and the conditioned medium, suggesting that the metal inhibited the synthesis of the glycosaminoglycan in growing endothelial cells. Inhibition of the [3H]thymidine incorporation by lead was significantly restored by heparin. Since the binding of bFGF to its receptor is strongly promoted by heparan sulfate, the present data suggest that lead inhibits vascular endothelial cell proliferation by induction of a lower response to endogenous bFGF through a suppression of heparan sulfate synthesis.

Animals↗

Lead inhibits the core protein synthesis of a large heparan sulfate proteoglycan perlecan by proliferating vascular endothelial cells in culture.

We characterized proteoglycans synthesized by growing cultured bovine aortic endothelial cells after exposure to lead. Lead significantly decreased the incorporation of both [3H]glucosamine and [35S]sulfate into glycosaminoglycans accumulated in the cell layer and the conditioned medium of the cells in a dose-dependent manner. Proteoglycans metabolically labeled with [35S]sulfate in the presence of lead were separated into heparan sulfate proteoglycans (HSPGs) and more highly charged chondroitin/dermatan sulfate proteoglycans by DEAE-Sephacel ion-exchange chromatography. It was found that lead markedly inhibited the synthesis of HSPGs. Sepharose CL-4B molecular sieve gel filtration showed that the marked decrease by lead occurred in the high molecular weight subclass of HSPGs. However, the length of heparan sulfate chains (approximately 50 kDa) was unchanged when analyzed by Sepharose CL-6B chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of core proteins showed that lead reduced the accumulation of a high molecular weight (approximately 400 kDa) HSPG core protein in the cell layer and the conditioned medium; the core protein was identified as a perlecan core by Western blot analysis. It is suggested that lead inhibits the synthesis of the perlecan core protein in growing endothelial cells without a change of heparan sulfate chain length. The present data support the hypothesis that inhibition of endothelial cell proliferation by lead may result from a lower response of the cells to endogenous basic fibroblast growth factor whose binding to the receptor is strongly promoted by heparan sulfate chains of perlecan.

Animals↗

Preoperative embolization of meningiomas with pial supply: successful treatment of two cases.

BACKGROUND: The efficacy of preoperative embolization for hypervascular meningiomas fed by the pial branches of the internal carotid artery was evaluated. METHODS: Two cases of hypervascular meningiomas fed by the cortical branches of the internal carotid arteries are presented. In the first patient, the left anterior frontal internal artery was embolized with gelatin sponge (Gelfoam) as a preoperative treatment using a microcatheter. The tumor was totally resected with 1,000 ml of blood loss. In the second patient, the right sulcal artery was embolized with Gelfoam. The patient subsequently underwent surgical resection with 100 mL of blood loss. RESULTS: No neurological deficit appeared after the embolization or the surgery in either case. CONCLUSION: Preoperative embolization of hypervascular meningiomas, mainly fed by the cortical branches of the internal carotid arteries, may be possible and effective.

Carotid Artery, Internal↗

Plasma fatty acids concentrations in postoperative patients with biliary atresia.

The concentrations of plasma fatty acids in postoperative patients with biliary atresia (BA) were measured to clarify whether they had essential fatty acid deficiency. Thirty-eight fasting blood samples from 14 postoperative patients with BA were studied. All of them had the hepatic portoenterostomy without any stoma. Samples were divided into three groups on the basis of liver function. The concentrations of fatty acids in the plasma fat were measured quantitatively. Non-essential fatty acids levels were increased and omega-3 fatty acids levels were decreased with the progress of deterioration of hepatic function. Regarding omega-6 fatty acids, C18:2 and 20:4 did not show any significant difference between the three groups and the control, and only C20:3 increased with the deterioration of liver dysfunction. The ratio of C20:3 (omega-6) to C20:4 (omega-6) was increased significantly with the progress of liver dysfunction. The activity of delta-5 desaturase was suspected to be suppressed in BA patients with poor liver function. The BA patients with poor bile flow did not show any decrease of omega-6 fatty acids in the plasma, but were at risk of developing omega-3 fatty acid deficiency.

Biliary Atresia↗

Clinical evaluation of the effect of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

The clinical efficacy of percutaneous transluminal angioplasty and intra-arterial papaverine infusion for treatment of vasospasm following subarachnoid hemorrhage was investigated. Between 1990 and 1993, 84 patients were treated for cerebral vasospasm in National Defense Medical College Hospital. Angioplasty was performed for asymptomatic vasospasm in 18 patients and for symptomatic vasospasm in 12 patients. Intra-arterial papaverine infusion was performed for asymptomatic vasospasm in 10 patients and for symptomatic vasospasm in four patients. The other 40 patients were treated with standard conservative therapy including hypervolemic and hypertensive hemodilution. The outcomes of these patients were analyzed using the Glasgow Outcome Scale. The outcome tended to be better for patients treated with angioplasty, but not for those treated with papaverine infusion, than for those treated conservatively. Recurrence of vasospasm was more frequent after papaverine infusion than after angioplasty. Undesirable complications such as abrupt development of unconsciousness were experienced during papaverine infusion but not during angioplasty. We conclude that percutaneous transluminal angioplasty is superior to intra-arterial papaverine infusion for prevention and treatment of vasospasm following aneurysmal subarachnoid hemorrhage.

Angioplasty, Balloon↗

Function of the propeptide region in recombinant expression of active procathepsin L in Escherichia coli.

In order to determine the functional role of the procathepsin L propeptide region for the preparation of active recombinant rat cathepsin L (CL), cDNAs encoding two short-length propeptides (C-terminal 2 and 27 residues) and the full-length (96 residues) one plus the entire CL were expressed as two soluble fusion proteins with a fragment of maltose-binding protein and an insoluble fusion protein with glutathione-S-transferase in Escherichia coli, respectively. After refolding of the insoluble fusion protein, each gene product was purified to homogeneity by amylose or glutathione-Sepharose-4B affinity column, and digestion with factor Xa and alpha-thrombin under alkaline conditions (pH approximately 8.0) led to the elution of two pure short-length procathepsin Ls (PCLs) and a full-length one, respectively. The enzymatic activity, estimated by hydrolytic assaying of benzoxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide under acidic conditions (pH 5.5), indicated that the two short-length PCLs exhibited in a great loss of the activity, as compared with the full-length PCL. The CD spectra of the short-length PCLs were different from that of the full-length one. The present results clearly show that the full-length propeptide is essential for construction of the active tertiary structure of CL at the stage of recombinant protein expression, although the expression of CL itself in E. coli does not require the propeptide. Based on the tertiary structure of PCL, the propeptide region necessary for the construction of the CL active structure has been discussed.

Animals↗

The morphological changes of exocrine pancreas in chronic pancreatitis.

The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBN/Kob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis.

Animals↗

Transcatheter embolization of a superior mesenteric artery pseudoaneurysm. A case report.

A 61-year-old man, with pseudoaneurysm of the superior mesenteric artery presenting with gastrointestinal bleeding, was successfully treated by transcatheter embolization using interlocking detachable coils. During the following observation time of 10 months, the patient had no sign of gastrointestinal bleeding. We underline the importance and feasibility of transcatheter embolization as the first-line treatment in such pseudoaneurysms.

Aneurysm, False↗

Role of autoantibodies against tubular brush border antigens in tubulointerstitial nephritis associated with Heymann nephritis.

Previous studies have shown that a rat experimental model of membranous nephropathy (Heymann nephritis) is often associated with tubulointerstitial changes. Although antibody-dependent tubular injuries have been proposed in this model, precise mechanisms have been ill-defined. In the present report, we established a model of acute tubulointerstitial nephritis (TIN) by injecting puromycin aminonucleoside (PAN) to Wistar rats which had been immunized with tubular antigens (Tub-Ag). In this model, TIN developed 4 weeks after Tub-Ag immunization when rats had a high titer of circulating anti-Tub-Ag antibodies and began to excrete massive proteinuria. Deposits of immunoglobulins along tubular brush borders were also demonstrated. Rats receiving either Tub-Ag or PAN alone failed to develop TIN during this relatively acute phase. These results suggest that anti-Tub-Ag antibodies excreted into the urine play a role in developing TIN in this model.

Animals↗

Artificial nine zinc-finger peptide with 30 base pair binding sites.

It is well-known that DNA binding of native nine zinc-finger protein TEIIIA is dominated by interaction of select few fingers. Newly designed zinc-finger peptide Sp1ZF9 containing nine Cys2-His2 type motifs has been manipulated. The DNA-binding property of Sp1ZF9 was compared with those of native three zinc-finger Sp1(530-623) and artificial six zinc-finger Sp1ZF6 peptides. Although the equilibrium time was less than 0.5 h for Sp1(530-623)-DNA complex, Sp1ZF6 and Sp1ZF9 required approximately 48 and 72 h, respectively, for full complex formation. Evidently, the footprinting analysis demonstrated that Sp1ZF9 and Sp1ZF6 bind at least 27 and 18 contiguous base pairs of DNA sequence, respectively. Sp1ZF9 showed two step bindings to DNA, namely first the recognition of GC (5'-GGG-GCG-GGGCC-3') sequence by the N-terminal Sp1 domain and next the recognition of the corresponding target sequences by the middle and C-terminal Sp1 domains. In contrast with unimolecular binding of Sp1ZF9 and Sp1ZF6, two Sp1(530-623) molecules bind to one GCIII (5'-GGG-GCG-GGG-GGG-GCG-GGG-GGG++ +-GCG-GGGCC-3') site region. Semispecific complex formed at the beginning of Sp1ZF9-DNA interaction has also been characterized by kinetic analysis using surface plasmon resonance. Interestingly, the association rate constants for GC and GCIII complexes of Sp1ZF9 are smaller than those of the corresponding Sp1(530-623) complexes. Of special interest is the fact that new nine zinc-finger peptide Sp1ZF9 can bind to DNA sequence of approximately 30 base pairs. Such multi zinc-finger peptides may be useful as genome-specific transcriptional switches in future.

Base Pairing↗

A miniature probe enables clear demonstration of the cystic duct during laparoscopic cholecystectomy.

We performed intraoperative ultrasonography with a miniature probe to explore the biliary anatomy, especially the cystic duct, during laparoscopic cholecystectomy. By using this radial-type probe introduced into a hard metal sheath with a balloon at the end, the plane containing Calot's triangle can be scanned easily when the gallbladder is extracted to the right side, thereby facilitating the identification of the cystic duct as well as the common ducts. In 30 cases, no common duct stone was found and the cystic duct was clearly identified. This radial-type miniature probe can be used to locate the cystic duct and avoid inadvertant incision or division of the common ducts.

Catheterization↗