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Biomedical subjects

H Kawanishi

Publications and source records attributed to H Kawanishi.

At least 19 recordsLinked to original sources
PubMed2006

Dicoumarol potentiates cisplatin-induced apoptosis mediated by c-Jun N-terminal kinase in p53 wild-type urogenital cancer cell lines.

3-3'-Methylene-bis [4-hydroxycoumarin] (dicoumarol), an inhibitor of NADPH:quinone oxidoreductase 1, has been reported to possess potential antineoplastic effects and the ability to abrogate p53 protein. In the present study, we investigated the cytotoxic effects of dicoumarol in combination with cisplatin (CDDP), using four bladder (RT112, 253J, J82 and UMUC3) and two prostate (LNCap and PC3) cancer cell lines. Single treatment with 100 microM dicoumarol suppressed cell proliferation but did not induce apoptosis at 24 h in all cell lines examined. On the other hand, pretreatment with dicoumarol enhanced cytotoxicity of CDDP in three cell lines with wild type of p53 (RT112, 253J and LNCap), but not in three other cell lines with mutant p53 or in RT112 stable transfectants with a dominant-negative mutant of p53. In RT112 and LNCap, CDDP induced p53 and p21 expression, while pretreatment of dicoumarol suppressed induction of p53/p21 and resulted in sequential activation of c-Jun N-terminal kinase (JNK) in a time-dependent manner. Furthermore, inhibition of JNK, using SP600125, completely suppressed activity of caspases and poly-(ADP-ribose) polymerase cleavage, leading to suppression of enhancement of CDDP-mediated apoptosis by dicoumarol. These results suggested that dicoumarol could enhance cytotoxicity of CDDP in urogenital cancer cells with wild-type p53 through the p53/p21/JNK pathways.

Antineoplastic Agents↗
PubMed2005

The pathogenesis and therapeutic option of encapsulating peritoneal sclerosis.

Since the first peritoneal dialysis (PD) patients with encapsulating peritoneal sclerosis (EPS) were reported in 1980, EPS has been considered primarily a fatal complication. The incidence of EPS in PD patients has been reported to be from 0.7% to 7.3%, and the rate appears to be higher in patients receiving long-term treatment. Most data from Japan has shown an overall incidence of 2.5% with an evident negative effect of increasing duration of PD, which also augments mortality. Since EPS occurred after withdrawal from PD in more than half of the patients, strict monitoring is necessary when a long-term PD patient is withdrawn from PD. Maintaining patients on standard PD for more than 8 years using conventional solutions is associated with a substantial risk for development of EPS. Appropriate treatment according to the disease stage is most important in EPS treatment. Therefore, when examining a PD patient complaining of gastrointestinal symptoms, the possibility of EPS has to be kept in mind. Basic therapeutic tactics for EPS include an appropriate use of steroids. If the state of bowel obstruction persists, laparotomy and enterolysis should be performed to obtain complete cure. It is now recognized that EPS is not a fatal complication of PD.

Adrenal Cortex Hormones↗
PubMed2004

Review of combination of peritoneal dialysis and hemodialysis as a modality of treatment for end-stage renal disease.

Because the contribution of residual renal function (RRF) to total solute clearance is often significant in continuous ambulatory peritoneal dialysis (CAPD), loss of RRF over time can lead to inadequate dialysis if appropriate prescription management strategies are not pursued. Additionally, declines in ultrafiltration caused by increases in peritoneal permeability may limit continuation of CAPD therapy. Peritoneal dialysis and hemodialysis (PD + HD) combination therapy (complementary dialysis therapy) is an alternative method. This therapy allows the patient to maintain daily activities, as with CAPD, while undergoing once-a-week HD supplements for the insufficient removal of solutes and water. This therapy allows for the continuation of PD without shifting to total HD in PD patients who continue to have uremic symptoms even after individualization of the PD prescription. This treatment option is psychologically more acceptable to patients and may be expected to provide such accompanying beneficial effects as peritoneal resting, improvement of QOL and reduction in medical cost.

Combined Modality Therapy↗
PubMed2001

Potent and selective ET-A antagonists. 2. Discovery and evaluation of potent and water soluble N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.

In the preceding article,(1) we outlined the discovery and structure-activity relationship of a potent and selective ET(A) receptor antagonist 1 and its related compounds. Metabolites of 1 having potent selective ET(A) receptor antagonist activity were identified. This study suggested the metabolic pathways of 1 were considerably affected by species. Consequently, structural modification of 1 intended to improve the complexity of the metabolic pathway, and water solubility was performed. The subsequent introduction of a hydroxyl group into the tert-butyl moiety of 1 led to the discovery of our new clinical candidate, 6b, which showed a higher water solubility, a uniform metabolic pathway among species, and very high affinity and selectivity for the human ET(A) receptor (K(i) for ET(A) receptor: 0.015 +/- 0.004 nM; for ET(B) receptor: 41 +/- 21 nM).

Animals↗
PubMed2001

Potent and selective ET-A antagonists. 1. Syntheses and structure-activity relationships of N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.

Modifications to the ET(A/B) mixed type compounds 1 (Ro. 46-2005) and 2 (bosentan) were performed. Introduction of a pyrimidine group into 1 resulted in a dramatic increase in affinity for the ET(A) receptor, and the subsequent optimization of substituents on the pyrimidine ring led us to the discovery of N-(6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-5-(4-methylphenyl)-4-pyrimidinyl)-4-tert-butylbenzenesulfonamide (7k), which showed an extremely high affinity for the human cloned ET(A) receptor (K(i) = 0.0042 +/- 0.0038 nM) and an ET(A/B) receptor selectivity up to 29 000 (K(i) = 130 +/- 50 nM for the human cloned ET(B) receptor). The compound was designed on the hypothesis that the hydrogen atom of the hydroxyl group in 1 and 2 played a role not as a proton donor but as an acceptor in the possible hydrogen bonding with Tyr129. Since the incorporation of a pyrimidinyl group into the hydroxyethoxy side chain of the nonselective antagonist (1) dramatically enhanced both the ET(A) receptor affinity and selectivity, and since similar results were obtained from the benzene analogues, we put forward the hypothesis that a "pyrimidine binding pocket" might exist in the ET(A) receptor.

Animals↗
PubMed2001

Statistical analysis of diagnostic failure of fine needle aspiration cytology (FNAC) in breast cancer.

Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among those, 57 cases failed in accurate diagnosis of malignancy and 243 were successful. Fourteen clinicopathological factors altogether were analyzed to elucidate any correlation with FNAC failure using uni- and multivariate analysis. The univariate analysis in each clinicopathlogical factor showed that these error cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers, small-sized of tumors, scattered type of cancer cell distribution in tumor tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with benign-like ultrasound findings and with low TNM stage. The multivariate analysis revealed tumor grade was the strongest factor for all, followed by cellular distribution type of cancer cells and benign-like ultrasound findings. From these results, we speculated that diagnostic failure of FNAC at first clinic visit seemed to be caused by mainly two histocytological factors: extrinsic factor (structural factors of tissue-like tumor cells' distribution pattern, etc.); and intrinsic one (cellular factors of low atypism such as benign-like ultrasound finding, low tumor grade, and so on).

Analysis of Variance↗
PubMed2001

Regioselectively substituted 6-O- and 2,3-di-O-acetyl-6-O-triphenylmethylcellulose: its chain dynamics and hydrophobic association in polar solvents.

Two kinds of regioselectively substituted cellulose derivatives, i.e., 6-O-triphenylmethylcellulose (6TC) and 2,3-di-O-acetyl-6-O-triphenylmethylcellulose (2,3Ac6TC), were prepared via cellulose. In these samples, C-6 position hydroxyls in the anhydroglucose units (AGU) along the cellulose chain were selectively substituted by the hydrophobic triphenylmethyl groups, but C-2 and -3 position hydroxyls remained in 6TC or were substituted completely by O-acetyls in 2,3Ac6TC. Their chain dynamics in polar solvents, dimethyl sulfoxide (DMSO) and N,N-dimethylacetamide (DMAc), in dilute solution were investigated by dynamic light scattering in the viewpoint of cluster formation. The results were compared with those of cellulose diacetates (CDA) in DMAc where three hydroxyls in the AGU were statistically substituted up to 2.44 by O-acetyls but hydroxyls at C-6 positions remained predominantly. It was found that 6TC and 2,3Ac6TC formed a dynamic structure about 10 times larger than single chains and that the structure would be a temporary and local association due to concentration fluctuations (dynamic structures) which were originated from the hydrophobic interactions between intermolecular triphenylmethyl groups. The dynamics and structures were in clear contrast to those of CDA where a solvent-mediated hydrogen bonding between intermolecular C-6 position hydroxyls was essential to cluster formation. The present structures were so weak as to dissipate easily under low shear field.

Macromolecular Substances↗
PubMed2001

A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge.

BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule. While ductography has been advocated as the main procedure in patients with nipple discharge, fiberoptic ductoscopy (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast through nipple orifice exploration. METHODS: We applied ductography and FDS to 65 women who had nipple discharge, and compared their utility. RESULTS: Intraductal lesions occurred in the segmental duct and the first, second, third, fourth, fifth, and sixth branches in decreasing frequency with ductography and FDS screening. The detection rates of intraductal abnormal lesions by ductography and FDS and the their combination were 89.1 (37 patients), 97.4 (38 patients), and 97.5% (39 patients) respectively. Ductal washings performed during FDS were effective to obtain representative exfoliated ductal cells which could be evaluated (sensitivity 50%, specificity 94.3%, and diagnostic accuracy 89.7%). As a result, we diagnosed 35 cases of benign lesions and four cases of malignant lesions by cytological or/and histological examination. CONCLUSION: Ductography and fiberoptic ductoscopy are useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge.

Adult↗
PubMed2001

[Bladder carcinoma producing granulocyte colony-stimulating factor (G-CSF): a case report].

An 84-year-old male was admitted to our hospital with complaints of leg edema and general fatigue. He had undergone transurethral resection of transitional cell bladder cancer, grade 3, pT1b, one year previously. The computed tomographic scan revealed a hypoattenuating bladder tumor, protruding extravesically. Laboratory examination showed remarkable leukocytosis of 46,900/mm3 in the peripheral blood and high value of granulocyte colony-stimulating factor (G-CSF) 226 pg/ml (normal: less than 30 pg/ml). The resection of the tumor (partial cystectomy) was performed. The histological diagnosis was transitional cell carcinoma, grade 3. The production of G-CSF was confirmed by immunohistochemical examination in the recurrent tumor and the surgical sample from the transurethral resection. The leukocyte count in the peripheral blood decreased to the normal range after surgery. But leukocytosis recurred one month postoperatively and the computed tomographic scan revealed intrapelvic tumor recurrence. He died due to drastic progression of recurrent tumor at three months postoperatively.

Aged↗
PubMed2001

Treatment options for encapsulating peritoneal sclerosis based on progressive stage.

Sclerosing encapsulating peritonitis (SEP) is recognized as a serious complication of peritoneal dialysis. However, recovery is possible if an appropriate diagnosis and treatment are made. The term SEP is used most often, but is inaccurate, particularly the reference to peritonitis. A more accurate description would be "encapsulating peritoneal sclerosis" (EPS). From the therapeutic perspective, the diagnosis should be established before EPS develops. Early diagnosis is important. Furthermore, it is also important to determine the therapeutic tactics for EPS according to the disease stage. Most cases of EPS develop with manifestations of fever, increased levels of C-reactive protein (CRP), and slight ileus symptoms, accompanied by increased ascites ("inflammatory stage"). Following precise identification of the inflammatory stage, steroid administration should be initiated immediately with the onset of EPS. Methylprednisolone pulse therapy is recommended during the early stage. If the EPS is not relieved, or if it recurs within 1 month, the steroid dose should be decreased and the patient should be managed by total parenteral nutrition (TPN) ("encapsulating stage"). If ileus symptoms remain despite the absence of inflammatory findings and decreased ascites, laparotomy and enterolysis should be considered within 6 months ("ileus stage"). However, it is important that the enterolysis be performed without damaging the capsule-covered intestine. To date, we have successfully treated EPS in 18 of 19 patients using these options. In 3 patients, EPS was relieved by steroid administration. In 15 patients, EPS was relieved by total intestinal enterolysis. Enterolysis patients had satisfactory operative outcomes and eventually returned to their previous social activities. One patient experienced perforation of the small intestine and pan-peritonitis, and died of sepsis. In summary, EPS is not an incurable disease. It can be completely overcome by active diagnosis and treatment.

Adolescent↗
PubMed2001

Low serum albumin in elderly continuous ambulatory peritoneal dialysis patients is attributable to high permeability of peritoneum.

Our study was carried out to investigate changes in nutrition and individual peritoneal membrane transport characteristics in elderly patients on continuous ambulatory peritoneal dialysis (CAPD), expressed as the personal dialysis capacity (PDC). We performed 376 PDC tests in 229 non diabetic patients who were undergoing CAPD from May 1995 to May 1999 in a multicenter study in Japan. We divided the patients into three groups: elderly (age > or = 65 years, n = 56), middle-aged (age 50-65 years, n = 150), and young (age < 50, n = 170). No significant differences were seen in duration of CAPD and incidence of peritonitis between the groups. We then compared the peritoneal function calculated by PDC test in the groups. Serum levels of albumin in elderly patients were significantly lower than those in middle-aged and young patients (elderly: 3.2 +/- 0.1; middle-aged: 3.4 +/- 0.1, p = 0.0447 vs elderly; young: 3.4 +/- 0.1, p = 0.0272 vs elderly). Plasma protein loss from the peritoneum in elderly patients was significantly higher than in middle-aged and young patients (elderly: 0.11 +/- 0.01; middle-aged: 0.09 +/- 0.01, p = 0.0136 vs elderly; young: 0.09 +/- 0.01, p = 0.0161 vs elderly). No significant differences in ultrafiltration volume and water permeability were seen between the groups. Peritoneal area in the elderly group was significantly higher than in the middle-aged and young groups. Peritoneal creatinine clearance (CCr) and Kt/V in elderly patients were significantly higher than in middle-aged and young patients. However, no significant difference in protein nitrogen appearance (PNA) or protein catabolic rate (PCR) was seen between the groups. Urea and creatinine generation rates in elderly patients were significantly lower than in the middle-aged and young patients. These data show that elderly patients receiving CAPD are well maintained from the perspective of urea and water metabolism, indicating that CAPD therapy for the elderly is more acceptable than expected. However, caution should be exercised, owing to the lower serum albumin seen in elderly patients.

Adult↗
PubMed2001

Encapsulating peritoneal sclerosis in Japan: prospective multicenter controlled study.

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is recognized as a serious complication of peritoneal dialysis. The aim of this study was to determine the incidence, clinical features, and variation in mortality rates for EPS. DESIGN: A prospective multicenter design was used, in which peritoneal dialysis patients were pre-registered by facilities across Japan and the incidence of EPS was observed in the registrants. The registrants were followed for a total of 4 years to accurately observe the onset of EPS. RESULTS: As of April 1999, 2216 peritoneal dialysis patients from 64 facilities were registered. By the end of March 2001, 332 patients had dropped out, and 17 of the dropouts had developed SEP. The incidence was 0.77%. After excluding 110 patients who died, the incidence in 2106 patients was 0.81%. The incidence of EPS increased with the duration of peritoneal dialysis. Of the 17 patients with EPS, 12 developed the condition after discontinuing peritoneal dialysis and changing to hemodialysis. During the 2-year survey period, 6 of the 17 EPS patients died. The interval from onset to death was 10.8 +/- 5.8 months (range: 3-19.5 months). CONCLUSIONS: From this prospective multicenter study, the current incidence of EPS is 0.77% (0.81% when dropout owing to death is censored). After a follow-up of 2 years, we conjecture that the incidence of EPS will increase. The incidence, etiology, and prognosis of EPS will be further clarified by periodic observation of dropouts until the end of March 2003.

Adult↗
PubMed2000

Follicular dendritic cell sarcoma: ultrastructural and immunohistochemical studies.

A rare case of follicular dendritic cell (FDC) sarcoma is reported. A 71-year-old woman was admitted for evaluation of constipation. Computerized tomography showed cervical, supraclavicular, retroperitoneal, and paraaortic lymphadenopathies. Histological findings from a cervical lymph node revealed Hodgkin's disease at first. But tumors that arose both in the cervical and the left interscapular regions during the chemotherapy were immunohistochemically confirmed to be of follicular dendritic cell origin. The ultrastructural findings were consistent with those of FDC sarcoma. FDC sarcoma is a rare nonlymphoid cell-derived malignant tumor originating from the lymphoid tissue. The diagnosis of FDC sarcoma is most accurately established by immunohistochemical methods, using its specific markers.

Aged↗
PubMed2000

Direct infusion of ascites into the blood circuit during hemodiafiltration in uremic patients with cirrhosis.

Two chronic dialysis patients with massive ascites caused by cirrhosis were treated by infusion of their ascites directly into the blood circuit. This stabilized their hemodynamics during dialysis, facilitating the control of weight gain and ascites, and thus markedly improving their general condition. Long-term use of this therapy was able to prevent the accumulation of ascitic fluid. Interestingly, fever occurred when this therapy was performed with hemodialysis, but not with hemofiltration or hemodiafiltration, suggesting that a pyrogen in the ascites was removed by filtration.

Aged↗
PubMed2000

[Bellini duct carcinoma of the kidney: a case report].

This is a report of a case of Bellini duct carcinoma of the kidney. A 72-year-old male was admitted to our hospital for the treatment of left renal tumor. The abdominal computed tomographic scan showed hypoattenuating tumor with infiltrative spread into the renal cortex. The renal angiography revealed a hypovascular tumor. Left nephro-ureterectomy was performed because transitional cell carcinoma was suspected in the frozen section. The gross examination revealed an infiltrating white-gray tumor centered in the renal medulla. No hemorrhage was discovered, but partial necrosis was found. Capsular infiltration was not seen. Histologically, tumor cells were mostly scattered and partially showed a papillary and tubular structure. Cells had abundant eosinophilic cytoplasm and large irregular nuclei. Immunohistochemical studies revealed positive reactions for cytokeratin, epithelial membrane antigen and ulex europaeus agglutinin. We diagnosed this patient with Bellini duct carcinoma. He died due to drastic progression of metastasis from carcinoma two months postoperatively.

Aged↗
PubMed2000

Necessity of correcting cancer antigen 125 appearance rates by body surface area.

Attention has been focused on cancer antigen 125 (CA125) levels in dialysate as an index for evaluating the severity of peritoneal mesothelial cell impairment. However, the method of evaluating CA125 levels in the dialysate has not been standardized. We determined that CA125 levels in the dialysate should be corrected by body surface area (BSA). Using 51 patients who had been undergoing peritoneal dialysis (PD), CA125 levels in the dialysate were measured to evaluate the appearance rate of CA125 (CA125AR). Because only 18 of the 51 patients (35%) had a BSA greater than 1.73 m2, CA125 levels in the dialysate might be underestimated in other patients when absolute values of CA125 are not corrected by BSA. When correlations between corrected CA125AR and various parameters were evaluated, corrected CA125AR positively correlated with age, but negatively correlated with serum creatinine and albumin levels. Moreover, no positive correlation was seen between corrected CA125AR and the duration of PD or the peritoneal permeability test. However, in 5 patients with ultrafiltration loss after prolonged PD, the values of CA125AR persistently or rapidly decreased before transfer to hemodialysis. Although CA125 can be used as an index of peritoneal deterioration, the absolute value of CA125 should be corrected by BSA. However, it is most important to evaluate changes in CA125 in individual patients.

Adult↗
PubMed2000

Surgical treatment for sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis (SEP) is recognized as a serious complication of continuous ambulatory peritoneal dialysis (CAPD). To date, in our hospital, 12 cases of SEP have been successfully treated by active intervention. The development of SEP was observed in these patients after removal of a peritoneal catheter. SEP was relieved by steroid administration in 3 of these patients, and by total parenteral nutrition (TPN) performed after exploratory laparotomy in 1 patient. In the remaining 8 patients, SEP was relieved by total intestinal enterolysis. In patients who underwent total intestinal enterolysis, the severity of encapsulation and adhesion varied. White, rigid encapsulation was observed in 4 patients who had been treated by peritoneal dialysis (PD) for less than 10 years. Seemingly normal serosae were observed under the capsules, and total intestinal enterolysis was easily performed in these patients. In the patient who underwent renal transplantation, more severe intestinal adhesion was observed, although the duration of PD was limited to 70 months and the intestinal serosae were seemingly normal. These findings were considered specific to SEP developing after immunosuppressant administration. In 3 patients who had undergone PD for more than 10 years, degeneration of the visceral peritoneum was observed, together with an ill-defined boundary between the capsules and the serosae. Therefore, total enterolysis was performed in these patients, including a wide area of the muscular layer. Furthermore, calcification was observed in several regions, where the capsules were severely adherent to the parietal peritoneum. The post-operative course for all 8 patients was satisfactory, and these patients finally returned to their previous social activities. We conclude that when SEP symptoms are not improved by steroid administration or TPN, active total intestinal enterolysis should be performed. However, it is absolutely important to avoid inducing anastomosis or impairing the intestine.

Adult↗