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Biomedical subjects

K Kawai

Publications and source records attributed to K Kawai.

At least 127 records · Page 7Linked to original sources

[Evidence-based medicine for urological cancer chemotherapy].

We reviewed the treatment results of urological cancer chemotherapy from the standpoint of evidence based medicine. In the treatment of advanced transitional cell carcinoma of the urothelium, M-VAC (MTX + VBL + ADM + CDDP) is regarded as the standard regimen; however, durable event-free survival is rare. There is no level 1 evidence to date showing that the use of neoadjuvant or adjuvant cisplatin-based regimens will improve survival in cases of locally advanced bladder cancer. Immunotherapy with interferon or interleukin-2 produces a small survival advantage in patients with metastatic renal cell carcinoma. There is no evidence that adjuvant interferon-alpha administration will improve the survival in those with non-metastatic renal cell carcinoma. Systematized cisplatin-based treatment protocols have been established in patients with advanced testicular germ cell tumor by means of many randomized controlled trials. Several clinical trials are under way to prove the efficacy of high dose chemotherapy (with autologous stem-cell support) in patients with poor risk germ cell tumors. We do not yet have sufficient data to conclude whether maximal androgen blockade will prolong the survival in patients with metastatic prostate cancer, nor to conclude whether neoadjuvant androgen depletion treatment improve disease free survival of the patients after radical prostatectomy.

Carcinoma, Transitional Cell↗

Development of a xylitol biosensor composed of xylitol dehydrogenase and diaphorase.

In preparation for the development of a xylitol biosensor, the xylitol dehydrogenase of Candida tropicalis IFO 0618 was partially purified and characterized. The optimal pH and temperature of the xylitol dehydrogenase were pH 8.0 and 50 degrees C, respectively. Of the various alcohols tested, xylitol was the most rapidly oxidized, with sorbitol and ribitol being reduced at 65% and 58% of the xylitol rate. The enzyme was completely inactive on arabitol, xylose, glucose, glycerol, and ethanol. The enzyme's xylitol oxidation favored the use of NAD+ (7.9 U/mg) over NADP+ (0.2 U/mg) as electron acceptor, while the reverse reaction, D-xylulose reduction, favored NADPH (7.7 U/mg) over NADH (0.2 U/mg) as electron donor. The K(m) values for xylitol and NAD+ were 49.8 mM and 38.2 microM, respectively. For the generation of the xylitol biosensor, the above xylitol dehydrogenase and a diaphorase were immobilized on bromocyan-activated sephallose. The gel was then attached on a dissolved oxygen electrode. In the presence of vitamin K3, NAD+ and phosphate buffer, the biosensor recorded a linear response to xylitol concentration up to 3 mM. The reaction was stable after 15 min. When the biosensor was applied to a flow injection system, optimal operation pH and temperature were 8.0 and 30 degrees C, respectively. The strengths and limitations of the xylitol biosensor are its high affinity for NAD+, slow reaction time, narrow linear range of detection, and moderate affinity for xylitol.

Biosensing Techniques↗

[Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid cancer--comparison study with 131I and 201Tl].

Detectability of metastasis in differentiated thyroid cancer using technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was compared with that of 131I and 201Tl. Forty patients after total thyroidectomy were evaluated. The scan results were compared with those of 131I and 201Tl whole body scintigraphy per patient. The positive rate was 68% in 99mTc-MIBI, 84% in 131I, 60% in 201Tl respectively. As to the lymph node metastasis, the positive rates were 56% in 99mTc-MIBI, 78% in 131I, 39% in 201Tl. In lung metastasis, the positive rate was 46% in 99mTc-MIBI, 82% in 131I and 55% in 201Tl. Serum thyroglobulin (Tg) was significantly higher in 201Tl and/or 99mTc-MIBI positive group compared to that of negative group independent of 131I scan results. Although the detectability of both 99mTc-MIBI and 201Tl were inferior to that of 131I, 9 to 22% of metastasis were detected only by these radiopharmaceuticals. Both 99mTc-MIBI and 201Tl, therefore, should be used in cases with high serum Tg even with negative 131I uptake. Basing on the fact there was no prominent difference between 99mTc-MIBI and 201Tl in the detectability of metastasis, 99mTc-MIBI might be more suitable tracer because of better quality image.

Adult↗

[Management of non-seminomatous germ cell tumors of the testes].

Since the advent of cisplatin-based chemotherapy in the 1970s, testicular cancer has become a model for curable cancer. We review the current treatment options for non-seminomatous germ cell tumors (NSGCT) of the testes. Surveillance is considered to be the most widely accepted option for stage I NSGCT in Japan. Because of the high relapse rate of about 30% in this setting, the establishment of a risk-adapted treatment protocol is warranted in stage I NSGCT. In early stage II NSGCT, both the primary RPLND and the primary chemotherapy show equivalent cure rates. These options give different balances of toxicity; namely, ejaculation disorders and drug induced infertility. In the treatment for NSGCT with good prognosis, both three courses of BEP and four courses of etoposide and cisplatin are appropriate and standard chemotherapy regimens.

Antineoplastic Agents, Phytogenic↗

Effect of surface roughness of porcelain on adhesion of bacteria and their synthesizing glucans.

STATEMENT OF PROBLEM: In some instances of porcelain restoration, refinishing is inevitable. In terms of plaque accumulation on porcelain, refinishing could be a substitute method for glazing. PURPOSE: This study compared the amount of adhesion of plaque components (bacterial cells and glucans) on porcelain disks with various degrees of surface roughness to assess the effects of surface roughness on the amount of plaque accumulation. MATERIAL AND METHODS: Radiolabeled cell suspensions were incubated with porcelain disks for 3, 8, and 24 hours at 37 degrees C, and the amounts of adhered cells and glucans were measured by using a liquid scintillation method. RESULTS: The amount of cells and glucans adhered on porcelain increased with incubation time. The surface roughness value and the amount of plaque adhesion decreased with the increase in polishing level. However, the greatest amount of plaque was adhered on glazed surfaces, although their surfaces were smoother than the surfaces polished with 120- or 600-grit abrasive papers. CONCLUSION: With the exception of glazed surfaces, a positive correlation between surface roughness and the amount of plaque accumulation was observed. Repolishing with a diamond paste would not induce problems of plaque accumulation, compared with an intact glazed surface.

Analysis of Variance↗

[Mild intermittent aspirin-induced asthma in a patient who became asymptomatic after removal of pet hamsters from home].

A 25-year-old woman was admitted to our hospital because of wheeze, dyspnea, nasal obstruction, epiphora, and ear fullness. These symptoms occurred 30 minutes after the intake of 200 mg of ibuprofen and 100 mg of norfloxacin, which had been prescribed by a local clinic for an upper respiratory tract infection. The patient had kept 20 hamsters indoors and a dog outside for 1 year and a half. During the 9 months prior to admission, she had experienced nocturnal asthmatic symptoms, which were controlled by oral theophylline on an as-needed basis. She had seasonal rhinitis, but no sinusitis or nasal polyps. Serum total IgE was 98 U/ml, and tests for specific IgE antibodies to hamster epithelium and dog epithelium were both positive (class 2). The provocative concentration of methacholine causing a 20% fall in FEV1 was 4.7 mg/ml. After removal of the hamsters from her home, the patient became asymptomatic without further medication, and her airway hyper-responsiveness was also alleviated. Although inhalation challenge with 5% tolmetin failed to induce a positive reaction, the diagnosis of aspirin-induced asthma was confirmed by single-blind oral challenge with 100 mg of ibuprofen. The patient exhibited mild airway responsiveness as well as mild sensitivity to nonsteroidal anti-inflammatory drugs, differing from the severe and intractable clinical features of typical aspirin-induced asthma.

Adult↗

[Cost-effectiveness of the treatment of reflux esophagitis: proton pump inhibitor versus histamine-2-receptor antagonist].

Gastroesophageal reflux disease(GERD) is a common condition and acid-suppressing agents are the mainstays of treatment. A clinical decision analysis comparing a proton pump inhibitor(PPI), lansoprazole and a histamine H2-receptor antagonist (H2RA), ranitidine for the treatment of reflux esophagitis in Japan was performed using a Markov chain approach. The PPI was consistently superior to the H2RA with regard to both clinical effectiveness and cost-effectiveness. Prescription of PPIs for a one-month period would further enhance the cost-effectiveness of PPI treatment. The PPI first strategy is the preferred therapeutic approach for medical treatment of reflux esophagitis. We also recommend that prescription of PPIs for a one-month period be approved by the Japanese health insurance scheme.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.

Adult↗

Isolation of different types of birnavirus from ayu Plecoglossus altivelis and amago salmon Oncorhynchus rhodurus cultured in the same geographic area.

A birnavirus was recently isolated from cultured ayu Plecoglossus altivelis on Shikoku island, Japan. The diseased fish displayed vertebral or vertical curvature and mild haemorrhage around the brain. Cytopathic effects (CPE) of the virus, including cell roundness, filamentous change and cell lysis, were observed in CHSE-214, RTG-2 and RSBK-2 cells. The virus isolated from ayu, designated the AY-98 strain, was found to be antigenically related to the marine birnavirus (MABV) Y-6 strain that originated from yellowtail Seriola quinqueradiata. AY-98 had a bi-segmented RNA genome and the same nucleotide sequence in the 310 bp VP2/NS junction as MABV Y-6. At the same time that the ayu epizootics occurred, another birnavirus (AM-98) was isolated from amago salmon Oncorhynchus rhodurus which were cultured 66 km away from the ayu farm. AM-98 showed a similar CPE and had the same host cell ranges as AY-98. However, AM-98 was serologically similar to the VR-299 strain of infectious pancreatic necrosis virus (IPNV) and their nucleotide sequences in the VP2/NS junction region showed 98% homology without changes at the amino acid level. In this study, the ayu strain AY-98 was grouped into MABV, whereas the amago salmon strain AM-98 was grouped into IPNV. This indicates that the 2 birnaviruses originated from different sources in spite of the fact that the places where they were isolated are close to one another. The results in this paper show a new aspect of the traditional consensus that the same serogroup of birnavirus distribute in close geographic areas.

Animals↗

Mutational analysis of the cardiac actin gene in familial and sporadic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) results in part from genetic disorders. Recently, missense mutations of the cardiac actin gene have been reported to cause DCM. We studied 136 Japanese DCM cases to elucidate how frequently the gene mutations are involved in its pathogenesis. Genomic DNA samples were obtained from 136 DCM cases (107 males, 29 females), containing 30 familial DCM (5 confirmed and 25 suspected). All six exons of the cardiac actin gene were analyzed by polymerase chain reaction, single-strand conformation polymorphism, and sequencing. We detected no mutations of the disease causation previously reported (G867A or A1014G) but two silent mutations (G979C and C1018T) in exon 6 and one point mutation (T1080A) in the 3'-untranslated region. As a result of screening 128 healthy subjects, these novel silent mutations were found to be mere genetic polymorphisms, not responsible for the disease. Although some genetic polymorphisms exist in the cardiac actin gene, mutations of the gene are rarely responsible for DCM, at least in the Japanese patients.

3' Untranslated Regions↗

Prevalence, predictors, and prognosis of reversal of maladaptive remodeling with intensive medical therapy in idiopathic dilated cardiomyopathy.

Some recent trials have shown that angiotensin-converting enzyme (ACE) inhibitors and/or beta blockers can improve left ventricular (LV) function and decrease LV mass in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prevalence and predictors of patients with IDC that showed marked reverse remodeling (a decrease in LV end-diastolic dimension > or = 5 mm to a final LV end-diastolic dimension < or = 55 mm and an increase in percent LV fractional shortening > or = 5% to a final percent fractional shortening of > or = 25% and a decrease in LV mass > or = 10%) after 2 years of intensive therapy with ACE inhibitors and/or beta blockers. In 78 patients with IDC (mean age 51 +/- 14 years), the clinical, echocardiographic, hemodynamic, laboratory, and endomyocardial biopsy data were evaluated at diagnosis and serial echocardiography was performed for 2 years. After 2 years of therapy, 20 of 78 patients (26%) showed marked reverse remodeling. Multivariate analysis revealed that higher systolic blood pressure (135 +/- 17 vs 120 +/- 16 mm Hg, p <0.001) and lower pulmonary arterial wedge pressure (7 +/- 3 vs 12 +/- 8 mm Hg, p <0.01) at diagnosis were independent predictors of reverse remodeling. Then, we further analyzed the prognosis of these patients for a mean of 50 +/- 32 months; 5-year survival (p <0.02) and event-free rates (p = 0.001) were better in patients with reverse remodeling than in patients without reverse remodeling.

Adrenergic beta-Antagonists↗

Enhanced phosphatidylinositol 3-kinase activity and high phosphorylation state of its downstream signalling molecules mediated by ret with the MEN 2B mutation.

We compared the intracellular signalling pathways through Ret tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF), multiple endocrine neoplasia (MEN) 2A, or MEN 2B mutation. Tyrosine phosphorylation of Grb2-associated binder-1 (Gab1) and activation of phosphatidylinositol 3-kinase (PI 3-kinase) were induced at higher levels by GDNF stimulation or the MEN 2B mutation than by the MEN 2A mutation. Tyrosine-phosphorylated Gab1 was a major component that interacted with the active PI 3-kinase in vivo. In addition, we found that p62Dok and PKB/Akt were phosphorylated in a PI 3-kinase-dependent manner and the levels of their phosphorylation were significantly higher in the MEN 2B transfectant than in the MEN 2A transfectant. Tyrosine phosphorylation of p62Dok resulted in its complex formation with the Ras GTPase-activating protein (RasGAP) and the Nck adaptor protein. These findings thus suggested that high levels of activation of PI 3-kinase and of phosphorylation of its downstream signalling molecules may be associated with the clinical phenotype of MEN 2B.

Adaptor Proteins, Signal Transducing↗

Cytotoxic pathways in the skin allograft rejection by CD4+ T cells.

BACKGROUND: Two major mechanisms of T cell-mediated cytotoxicity are known: perforin-dependent and Fas-dependent cytotoxic pathways. Previous studies in vitro demonstrated that CD4+ cytotoxic T lymphocytes use the Fas pathway as a primary cytotoxic mechanism, but the cytotoxic mechanisms used by CD4+ T cells in vivo are unclear. METHODS: We examined the cytotoxic pathways of CD4+ T cells in vivo using a skin allograft model, in which athymic nu/nu mice were transplanted with skin allografts and reconstituted with purified CD4+T cells. Fas-deficient and perforin-deficient mice and anti-tumor necrosis factor (TNF)-alpha monoclonal antibody were used for inactivating each cytotoxic pathway in vivo. RESULTS: The skin allografts from Fas-deficient mice were readily rejected by the athymic mice reconstituted with purified CD4+ T cells. Perforin-deficient CD4+ T cells could also reject Fas-deficient skin allografts. Furthermore, in vivo treatment with anti-TNF-alpha monoclonal antibody did not prevent the allograft rejection by CD4+ T cells in the absence of both Fas and perforin pathways. CONCLUSIONS: These results indicate participation of undefined mechanisms other than Fas, perforin, and TNF-alpha pathways in CD4+ T cell-mediated cytotoxicity in vivo.

Animals↗

Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma.

Several mutations were identified in the kinase domain of the RET proto-oncogene in patients with multiple endocrine neoplasia (MEN) 2B, familial medullary thyroid carcinoma (FMTC) or sporadic medullary thyroid carcinoma. We introduced seven mutations (glutamic acid 768-->aspartic acid (E768D), valine 804-->leucine (V804L), alanine 883-->phenylalanine (A883F), serine 891-->alanine (S891A), methionine 918-->threonine (M918T), alanine 919-->proline (A919P) and E768D/A919P) into the short and long isoforms of RET cDNA and transfected the mutant cDNAs into NIH3T3 cells. The transforming activity of the long isoform of Ret with each mutation was much higher that that of its short isoform. Based on the levels of the transforming activity, these mutant RET genes were classified into two groups; a group with high transforming activity (A883F, M918T and E768D/A919P) and a group with low transforming activity (E768D, V804L, S891A and A919P) (designated high group and low group). Interestingly, the level of transforming activity correlated with clinical phenotypes; high group Ret with the A883F or M918T mutation and low group Ret with the E768D, V804L or S891A mutation were associated with the development of MEN 2B and FMTC, respectively. In addition, we found that substitution of phenylalanine for tyrosine 905 present in the kinase domain abolished both transforming and autophosphorylation activities of low group Ret whereas it did not affect the activities of high group Ret.

Amino Acid Substitution↗

The excitability of a motoneuron pool assessed by the H-reflex method is correlated with the susceptibility of Ia terminals to repetitive discharges in humans.

The correlation of the degree of the Hoffmann (H-) reflex depression induced by a passive stretch of the soleus muscle (Sol) and the excitability of the motoneuron (MN) pool was investigated in 24 healthy human subjects. The excitability of the Sol MN pool was determined by the ratio of the slope of the H-reflex (Hslp) and M-response recruitment curves (Mslp). The Hslp/Mslp ratio was decreased by a passive stretch of the Sol given 1 s before the H-reflex stimulus, and was significantly correlated with the amount of the H-reflex depression. These results suggest that the excitability of the MN pool assessed by the H-reflex method depends on the presynaptic mechanism involved in the efficiency of transmission across the synapses of Ia afferents in response to repetitive discharge.

Adult↗

Establishment and characterization of a second primary osteosarcoma cell line (OSrb/N-M) from a patient cured of bilateral retinoblastoma.

A cell line, designated OSrb/N-M, was established from the second primary osteosarcoma that developed in a 17-year-old Japanese female patient who had suffered from bilateral retinoblastoma at infancy. The OSrb/N-M cells grew as an adherent monolayer and retained some osteogenic biochemical phenotypes. In cytogenetic analyses, this cell line revealed many structural and numerical abnormalities, however, the bands q14 of both chromosomes 13 appeared to be normal, whereas the constitutional cells displayed normal female karyotypes. Immunoblot studies using monoclonal antibodies specific to RB protein demonstrated that the tumor cells did not express RB protein, suggesting that the OSrb/N-M cells might suffer from a loss-of-function mutation at this gene locus. Thus, this cell line is useful to study the molecular mechanism for the tumorigenesis of osteosarcoma with regard to an association with retinoblastoma.

Adolescent↗

New methods of control against postoperative methicillin-resistant Staphylococcus aureus infection.

The incidence of postoperative infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan has been increasing dramatically. In March 1990, we assigned special doctors in infection control (infection control doctor, ICD), and defined comprehensive controls against MRSA infection. A total of 3536 cases of digestive tract surgery performed at our department were studied during the period between September 1987 and August 1997. We changed the use of antibiotics to prevent postoperative infection. Cefazolin (CEZ) was employed for surgery of the upper digestive tract, including esophagus, stomach, duodenum, and gallbladder. Cefotiam (CTM) was employed for surgery of the lower digestive tract, liver, and pancreas. In esophageal resection, the tracheal tube was extracted during the early postoperative period, and for cervical esophagogastroanastomosis, the autosuture was changed to layer-to-layer anastomosis. We have achieved successful control of postoperative MRSA infection, the incidence having decreased to 0.3% (9/2703). In conclusion, our methods of control against postoperative MRSA infection implies that comprehensive measures of prevention, including the reviewed specification and usage of antibiotics and operation management, have been well implemented. This value is the lowest and the first of any domestic hospital or institute in Japan, suggesting a continued and significant decrease.

Cephalosporins↗