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Biomedical subjects

K Takase

Publications and source records attributed to K Takase.

At least 55 records · Page 3Linked to original sources

Prospective study of laparoscopic findings with regard to the development of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis.

BACKGROUND: The laparoscopic findings of hepatocarcinogenesis are not well defined. The purpose of this prospective study was to evaluate the predictive value of laparoscopic findings with regard to the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-associated cirrhosis. METHODS: One hundred nineteen patients with HCV-associated cirrhosis who underwent laparoscopy were enrolled in this study. Ten laparoscopic variables, including degree of development and size of regenerating nodules, irregularity of regenerating nodules, and size of both hepatic lobes, were measured. The predictive value of each finding for the development of HCC was investigated by using univariate and multivariate analyses. RESULTS: HCC developed in a total of 42 of the 119 patients (35.3%) during a mean follow-up period of 62.9 months. The degree of regenerating nodules, the presence of irregular regenerative nodules, and atrophic right lobe were significant predictive factors for HCC with univariate analysis. In particular, 67.1% of patients with irregular regenerative nodules had HCC develop within 5 years. Multivariate analysis revealed that irregular regenerative nodules (relative risk 6.32, p = 0.012), the degree of regenerative nodules (relative risk 4.78, p = 0.029), and atrophic right lobe (relative risk 3.87, p = 0.048) were independent predictive factors. CONCLUSIONS: Morphologic observation of the liver surface by laparoscopy is important and provides information on factors that are statistically significant early predictors of the development of HCC.

Adult↗

Crystal structure of Bacillus stearothermophilus alpha-amylase: possible factors determining the thermostability.

The crystal structure of a thermostable alpha-amylase from Bacillus stearothermophilus (BSTA) has been determined at 2.0 A resolution. The main-chain fold is almost identical to that of the known crystal structure of Bacillus licheniformis alpha-amylase (BLA). BLA is known to be more stable than BSTA. A structural comparison between the crystal structures of BSTA and BLA showed significant differences that may account for the difference in their thermostabilities, as follows. (i) The two-residue insertion in BSTA, Ile181-Gly182, pushes away the spatially contacting region including Asp207, which corresponds to Ca(2+)-coordinating Asp204 in BLA. As a result, Asp207 cannot coordinate the Ca(2+). (ii) BSTA contains nine fewer hydrogen bonds than BLA, which costs about 12 kcal/mol. This tendency is prominent in the (beta/alpha)(8)-barrel, where 10 fewer hydrogen bonds were observed in BSTA. BLA forms a denser hydrogen bond network in the inter-helical region, which may stabilize alpha-helices in the barrel. (iii) A few small voids observed in the alpha-helical region of the (beta/alpha)(8)-barrel in BSTA decrease inter-helical compactness and hydrophobic interactions. (iv) The solvent-accessible surface area of charged residues in BLA is about two times larger than that in BSTA.

Amino Acid Sequence↗

Lunate excision, capitate osteotomy, and intercarpal arthrodesis for advanced Kienböck disease. Long-term follow-up.

BACKGROUND: Kienböck disease is caused by aseptic necrosis of the lunate. In the advanced stages of the disease, carpal collapse, joint incongruity, and osteoarthritis develop. We performed lunate excision, capitate osteotomy, and intercarpal arthrodesis (the modified procedure of Graner et al.) on fifteen patients with stage-IIIB or IV Kienböck disease. This report is a review of the findings in these patients. METHODS: The subjects ranged in age from twenty-six to fifty-four years (mean, 39.2 years) at the time of surgery. We evaluated the results more than five years postoperatively (range, sixty-two to 145 months postoperatively; mean, 79.3 months postoperatively). Therapeutic results were evaluated according to the scoring system of Evans et al. RESULTS: Pain disappeared after surgery in most patients. Others had a reduction in the intensity of the pain to a mild level. The grip strength on the affected side had recovered to about 80% of that on the unaffected side twelve months after surgery. The long-term results were graded as good in eleven of the patients, as fair in two, and as poor in two. Postoperative radiographs showed that the carpal bone parameters (carpal height index and radioscaphoid angle) had improved. Radiographic osteoarthritic changes occurred in all of the patients; however, except for moderate limitation of the range of motion at the wrist joint, these findings did not affect the level of pain, grip strength, or activities of daily living. CONCLUSIONS: Lunate excision followed by capitate osteotomy and intercarpal arthrodesis (the modified procedure of Graner et al.) is a reliable form of treatment for advanced Kienböck disease, with favorable results for at least five years postoperatively.

Activities of Daily Living↗

Electrophoretic mobility shift scanning using an automated infrared DNA sequencer.

Electrophoretic mobility shift assay (EMSA) is widely used in the study of sequence-specific DNA-binding proteins, including transcription factors and mismatch binding proteins. We have established a non-radioisotope-based protocol for EMSA that features an automated DNA sequencer with an infrared fluorescent dye (IRDye) detection unit. Our modification of the elec- trophoresis unit, which includes cooling the gel plates with a reduced well-to-read length, has made it possible to detect shifted bands within 1 h. Further, we have developed a rapid ligation-based method for generating IRDye-labeled probes with an approximately 60% cost reduction. This method has the advantages of real-time scanning, stability of labeled probes, and better safety associated with nonradioactive methods of detection. Analysis of a promoter from an industrially important filamentous fungus, Aspergillus oryzae, in a prototype experiment revealed that the method we describe has potential for use in systematic scanning and identification of the functionally important elements to which cellular factors bind in a sequence-specific manner.

DNA↗

"Variable echo sign" (ultrasonographical alteration of echogenicity) in cavernous hepatic hemangioma.

There are few reports describing cavernous hepatic hemangiomas with alteration of ultrasonographical imaging during examinations. We performed ultrasonographic examination of 64 cavernous hepatic hemangiomas and recognized 26 cases (41%) with an alteration of echogenicity during the examinations. We refer to this alteration of echogenicity of cavernous hepatic hemangioma as a "variable echo sign". We performed angiography of the cavernous hepatic hemangiomas with variable echo sign. Most of these imaging patterns showed mild or moderate pooling, suggesting that the alteration of echogenicity might be based on a slow blood flow exchange. We suggest that a variable echo sign is specific to ultrasonographic imaging with cavernous hepatic hemangioma and may be useful to differentiate cavernous hepatic hemangioma from other tumors.

Adult↗

Combining transcatheter arterial chemoembolization with percutaneous ethanol injection therapy for small size hepatocellular carcinoma.

For patients with unresectable small size HCC, percutaneous ethanol injection therapy (PEIT) is used as a non-surgical treatment because it is difficult to achieve complete tumor necrosis by transcatheter arterial chemoembolization (TAE) alone. However, some small HCCs (<21 mm in diameter) are resistant to PEIT with incomplete tumor necrosis, which is associated with insufficient ethanol injection to the tumor. For more effective treatment for HCC, we performed a combination of TAE and PEIT on patients with small size HCC and evaluated the cumulative recurrence and survival rates. The recurrence rate in patients treated with the combination was less than that of TAE or PEIT alone. There were five patients without tumor recurrence during the follow-up period and three out of these underwent the combination treatment. The period of no recurrence was 33.4 months on average. In conclusion, we recommend combination therapy with TAE and PEIT for patients to accomplish more effective treatment of small size HCC.

Administration, Cutaneous↗

[Clinicopathological study of influential factors on prognosis in patients with renal cell carcinoma].

Between January 1986 and August 1996, 120 patients were diagnosed with renal cell carcinoma (RCC) at Kanagawa Cancer Center. In this study, we analyzed these patients in view of the clinicopathological factors, which affect the prognosis of these patients with univariate and multivariate analysis using Cox's proportional hazard model. Of these 120 patients, 40 patients (33%) died of RCC during this period. The cause specific survival rate was 65% after 5 years and 57% after 10 years. Univariate analysis showed some factors, performance status, symptoms, tumor size, histological grade, local invasion (pT), venous involvement (pV), lung metastasis, lymph-node metastasis, and bone metastasis, affected the prognosis. Furthermore, multivariate analysis using Cox's proportional hazard model showed that performance status, pT, pV, lung metastasis, lymphnode metastasis, and bone metastasis independently affected the prognosis. In summary, TMN factors and performance status importantly affect the prognosis of RCC patients.

Carcinoma, Renal Cell↗

[Study of neoadjuvant chemotherapy for invasive bladder cancer with MEC (methotrexate, epirubicin, cisplatin) therapy].

Eighteen patients with locally invasive bladder cancer were treated with 1 or 2 cycles of neoadjuvant chemotherapy consisting of methotrexate, epirubicin and cisplatin (MEC). All patients underwent radical cystectomy and pelvic lymph node dissection. Down-staging was observed in twelve (complete pathological response in 3 and partial pathological response in 9) patients (response rate were 67%). Four of the 18 patients died of disease and all of them had not achieved down-staging. Multivariate analysis revealed nodal status to be the only independent predictor. With regard to side effects, gastrointestinal symptoms and myelo-suppression were observed in almost all patients. Thrombocytopenia was observed in 13 patients (72%) including 7 patients who showed symptoms over grade 3. Gastro-intestinal symptoms and leukocytopenia disappeared with granisetron and granulocyte colony stimulating factor. There were no treatment-related deaths in this study. These results indicate that MEC therapy was safely performed and showed a high response rate in patients with locally invasive bladder cancer.

Aged↗

[A case of Gerstmann-Sträussler-Scheinker syndrome (GSS) with late onset--a haplotype analysis of Glu219Lys polymorphism in PrP gene].

We report a 74-year-old man with late onset Gerstmann-Sträussler-Scheinker syndrome (GSS). In this family, 3 out of 6 siblings and his father developed cerebellar ataxia and mental deterioration in their fifth decades. He complained of unsteady walking and tingling pain in the legs at the age of 70. Neurological examination revealed moderate truncal ataxia, mild limb ataxia, ataxic speech, sensory impairment, paresthesia and areflexia in the lower extremities. CSF examination showed elevated CSF and 14-3-3 proteins with a normal cell count. EEG and brain MRI demonstrated no abnormality. Somatosensory evoked potential (SEP) study showed delayed N13-N20 interpeak latencies in the upper extremities and delayed N20 at 12th thoracic spinous process, indicating dysfunction of the posterior roots or columns of the spinal cord including the dorsal horns and proximal peripheral nerve. Analysis of the prion protein gene demonstrated a Pro102Leu amino acid substitution, which is compatible with classical GSS. Haplotype analysis of the PrP gene identified a Glu219Lys polymorphism on another allele. Recently, it was confirmed that protein X, which accelerates the conversion of the normal type of PrP (PrPC) into a pathological type of PrP (PrPSc), binds to the 219th amino acid residue of PrP. Therefore, the 219Lys polymorphism theoretically inhibited formation of PrPSc and may thus have delayed the onset of the disease in this patient.

Aged↗

[Cooperative medical care by physicians of general hospitals and psychiatrists of an alcoholism treatment unit in Mie Prefecture].

Clinical practice of psychiatric liaison with physicians is the first step for an early treatment of alcohol dependence. Screening patients with alcohol dependence in general hospitals, carrying out intervention, and referring them to psychiatric specialists are running smoothly by the cooperation of member of the Mie Association for the Study of Alcohol-related Diseases. This association is being conducted by managers constituted of doctors, nurses, and medical social workers and the meeting is held every 6 months at district general hospitals to achieve three objectives; 1) evoking a sense of responsibility for alcoholic patients in the mind of general hospital staffs, 2) developing a network for psychiatric liaison with physicians to care patients of their alcohol dependence, and 3) keeping up activities of the association. We have already held the regular meeting 12 times, and prepared pamphlets for screening alcohol misuse and for early intervention. A course for learning skills of early intervention in this summer won the favor of participants. Through case conference of alcoholism and full accounts of the experiences given by recovered patients or their families, meeting attendants know patients' distress, families' sorrow, and their delight brought by the recovery, and are motivated to assist patients with alcohol dependence. Thus, "Spirit to Spirit" is a keyword to develop a network of the cooperative medical care for supporting patients with alcohol dependence. Referral of alcoholic patients to psychiatrists and/or psychiatric liaison therapy is promoted by a reliable, faithful, and face to face relationship between physicians and psychiatrists. Physicians' learning the skill for early intervention in alcohol dependence is followed by an increase in referral of patients to psychiatrists, and which suggests the importance of providing teaching and training of medical care for alcohol dependence to medical staffs including doctors of emergency care units, orthopedics, obstetrics, and dentistry. Therefore, systematic tools for screening alcohol dependence in general practice, and for referring patients to psychiatrics after brief intervention are needed to be prepared under the leadership of a learned society. Popularizing the skill of brief intervention in general medical practice is also indispensable for advising alcoholic patients about changing their drinking pattern or abstinence.

Alcoholism↗

Cell surface expression of calnexin, a molecular chaperone in the endoplasmic reticulum.

The folding and assembly of nascent proteins in the endoplasmic reticulum are assisted by the molecular chaperone calnexin, which is itself retained within the endoplasmic reticulum. It was up to now assumed that calnexin was selectively expressed on the surface of immature thymocytes because of a particular characteristic of the protein sorting machinery in these cells. We now report that a small fraction of calnexin is normally expressed on the surface of various cells such as mastocytoma cells, murine splenocytes, fibroblast cells, and human HeLa cells. Surface biotinylation followed by chase culture of living cells revealed that calnexin is continuously delivered to the cell surface and then internalized for lysosomal degradation. These results suggest that there is continuous exocytosis and endocytosis of calnexin, and the amount of calnexin on the plasma membrane results from the balance of the rates of these two events. To study the structural requirement of calnexin for surface expression, we created deletion mutants of calnexin and found that the luminal domain, particularly the glycoprotein binding domain, is necessary. These findings suggest that the surface expression of calnexin depends on the association with glycoproteins and that calnexin may play a certain role as a chaperone on the plasma membrane as well.

Amino Acid Motifs↗

Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase N.

CPI-17 is a phosphorylation-dependent inhibitory protein for smooth muscle myosin phosphate. Phosphorylation at Thr(38), in vitro, by protein kinase C or Rho-kinase enhances the inhibitory potency toward myosin phosphatase. Phosphorylation of CPI-17 by protein kinase N (PKN), a fatty acid- and Rho-activated serine/threonine kinase, and its effect on smooth muscle myosin phosphatase activity were investigated. CPI-17 was phosphorylated by GST-PKN-CAT, a constitutively active GST-fusion fragment of PKN, to 1.46 mol of P/mol of CPI-17, in vitro. The K(m) value of CPI-17 for PKN was 0.96 microM. Phosphorylation of PKN dramatically increased the inhibitory effect of CPI-17 on myosin phosphatase activity. The major and inhibitory phosphorylation site was identified as Thr(38) using a point mutant of CPI-17 and a phosphorylation-state specific antibody. Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho and/or arachidonic acid.

Animals↗

Phosphorylation of CPI-17, an inhibitory phosphoprotein of smooth muscle myosin phosphatase, by Rho-kinase.

Phosphorylation of CPI-17 by Rho-associated kinase (Rho-kinase) and its effect on myosin phosphatase (MP) activity were investigated. CPI-17 was phosphorylated by Rho-kinase to 0.92 mol of P/mol of CPI-17 in vitro. The inhibitory phosphorylation site was Thr(38) (as reported previously) and was identified using a point mutant of CPI-17 and a phosphorylation state-specific antibody. Phosphorylation by Rho-kinase dramatically increased the inhibitory effect of CPI-17 on MP activity. Thus, CPI-17 as a substrate of Rho-kinase could be involved in the Ca(2+) sensitization of smooth muscle contraction as a downstream effector of Rho-kinase.

Animals↗

Clinical, cardiopulmonary, hematological and serum biochemical effects of sevoflurane and isoflurane anesthesia in oxygen under spontaneous breathing in sheep.

Effects of sevoflurane and isoflurane anesthesia in oxygen on clinical, cardiopulmonary, hematological, and serum biochemical findings were compared in sheep breathing spontaneously undergoing minor surgical operations during short-term (60-80min) or long-term (3-4h) anesthesia. All sheep were premedicated with atropine sulfate (0.1mg/kg) intramuscularly, and 10min later, induced to anesthesia by intravenous infusion of sodium thiopental (mean 14.1+/-3.4 S.D. mg/kg). After intubation, they were anesthetized with either isoflurane or sevoflurane in oxygen at a total gas flow rate of 1.5l/min. The results revealed that recovery time with sevoflurane was more rapid than with isoflurane. Respiration rates, tidal volume, minute ventilation and heart rates during sevoflurane anesthesia were similar to those during isoflurane anesthesia. The degree of respiratory acidosis during sevoflurane anesthesia was also similar to that during isoflurane anesthesia. There were no significant differences between sevoflurane and isoflurane anesthesia in hematological and serum biochemical values.

Journal Article↗

Pancreatitis-associated ascitic fluid increases intracellular Ca(2+) concentration on hepatocytes.

BACKGROUND: We have reported that pancreatitis-associated ascitic fluid (PAAF) contains a cytotoxic factor(s) inducing apoptosis on renal tubular cells and hepatocytes. It has been suggested that elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) is associated with the development of cell damage and apoptosis. METHODS: To clarify the mechanism of hepatocellular injury in acute pancreatitis, the effect of PAAF on hepatocyte [Ca(2+)](i) was investigated. Primary cultures of rat hepatocytes were loaded with Fura-2/acetoxymethyl, and the changes of [Ca(2+)](i) were measured using spectrofluorometer. RESULTS: The baseline of hepatocyte [Ca(2+)](i) was 172 +/- 17 nM. [Ca(2+)](i) increased from 1 min after the addition of PAAF in a dose-dependent manner. Fractionation of PAAF revealed only one fraction (molecular weight >/= 5 x 10(4)) possessed both [Ca(2+)](i) elevation activity and cytotoxic activity. Neither 8-(N,N-diethyl-amino) octyl-3,4,5-trimethoxybenzoate (TMB-8) nor thapsigargin inhibited the PAAF-evoked [Ca(2+)](i) elevation. Chelation of extracellular Ca(2+) by ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) prevented the elevation of [Ca(2+)](i), but verapamil did not prevent it. Platelet-activating factor antagonist (TCV-309) blocked the PAAF-elicited [Ca(2+)](i) elevation. Pancreatitis-associated serum also increased hepatocyte [Ca(2+)](i). Moreover, PAAF increased [Ca(2+)](i) on Madin-Darby canine kidney cells in a dose-dependent manner. CONCLUSIONS: These results suggest that the dramatic elevation of hepatocyte [Ca(2+)](i) due to PAAF may be closely related to the hepatocellular injury in severe acute pancreatitis and that platelet-activating factor may play a pivotal role in increasing hepatocyte [Ca(2+)](i). Elevation of [Ca(2+)](i) in various cells may be involved in the mechanism of multiple organ failure in this disease.

Acute Disease↗

C-ERBB-2 gene amplification as a prognostic marker in human bladder cancer.

OBJECTIVES: To evaluate c-erbB-2 gene amplification and its prognostic significance in transitional cell carcinoma of the bladder. METHODS: Alterations in the gene copy number of c-erbB-2 were detected in 57 bladder tumor samples using a method based on the polymerase chain reaction. RESULTS: Eighteen tumors (32%) showed gene amplification of c-erbB-2, which correlated with tumor grade and stage. A strong association of c-erbB-2 amplification with patient survival was also found. The amplification resulted in a significantly poorer prognosis among the patients with high-grade and/or invasive tumors. Multivariate analysis revealed that c-erbB-2 amplification and tumor grade were independent prognostic factors. CONCLUSIONS: Our data indicate a possible role of the c-erbB-2 gene in the development of aggressive behavior in bladder tumors. Moreover, the use of c-erbB-2 gene amplification, together with tumor grade and stage, could provide an accurate basis for determining the prognosis of bladder cancer.

Adult↗