Biomedical subjects

K Fujikawa

Publications and source records attributed to K Fujikawa.

At least 91 records · Page 5Linked to original sources

PubMed1999

The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein.

The possibility that Escherichia coli MutT and human MTH1 (hMTH1) hydrolyze oxidized DNA precursors other than 8-hydroxy-dGTP (8-OH-dGTP) was investigated. We report here that hMTH1 hydrolyzed 2-hydroxy-dATP (2-OH-dATP) and 8-hydroxy-dATP (8-OH-dATP), oxidized forms of dATP, but not (R)-8,5'-cyclo-dATP, 5-hydroxy-dCTP, and 5-formyl-dUTP. The kinetic parameters indicated that 2-OH-dATP was hydrolyzed more efficiently and with higher affinity than 8-OH-dGTP. 8-OH-dATP was hydrolyzed as efficiently as 8-OH-dGTP. The preferential hydrolysis of 2-OH-dATP over 8-OH-dGTP was observed at all of the pH values tested (pH 7.2 to pH 8.8). In particular, a 5-fold difference in the hydrolysis efficiencies for 2-OH-dATP over 8-OH-dGTP was found at pH 7.2. However, E. coli MutT had no hydrolysis activity for either 2-OH-dATP or 8-OH-dATP. Thus, E. coli MutT is an imperfect counterpart for hMTH1. Furthermore, we found that 2-hydroxy-dADP and 8-hydroxy-dGDP competitively inhibited both the 2-OH-dATP hydrolase and 8-OH-dGTP hydrolase activities of hMTH1. The inhibitory effects of 2-hydroxy-dADP were 3-fold stronger than those of 8-hydroxy-dGDP. These results suggest that the three damaged nucleotides share the same recognition site of hMTH1 and that it is a more important sanitization enzyme than expected thus far.

Bacterial Proteins↗

PubMed1999

The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP.

The genotoxicity of 30 aromatic amines selected from IARC (International Agency for Research on Cancer) groups 1, 2A, 2B and 3 and from the U.S. NTP (National Toxicology Program) carcinogenicity database were evaluated using the alkaline single cell gel electrophoresis (SCG) (Comet) assay in mouse organs. We treated groups of four mice once orally at the maximum tolerated dose (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow 3, 8 and 24 h after treatment. For the 20 aromatic amines that are rodent carcinogens, the assay was positive in at least one organ, suggesting a high predictive ability for the assay. For most of the SCG-positive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Organ-specific genotoxicity, therefore, is necessary but not sufficient for the prediction of organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amines (eight were Ames test-positive and two were Ames test-negative), the assay was negative in all organs studied. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic in vivo. Chemical carcinogens can be classified as genotoxic (Ames test-positive) and putative non-genotoxic (Ames test-negative) carcinogens. The alkaline SCG assay, which detects DNA lesions, is not suitable for identifying non-genotoxic carcinogens. The present SCG study revealed a high positive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic non-carcinogens. These results suggest that the alkaline SCG assay can be usefully used to evaluate the in vivo genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.

Amines↗

PubMed1999

Expression of functional CD40 in human hepatocellular carcinoma.

CD40, a member of the tumor necrosis factor receptor (TNFR) family, plays a crucial role in the survival, proliferation, and differentiation in B cells. However, the expression of CD40 other than in B cells has not been well studied. Therefore, we investigated the expression and function of CD40 in hepatocellular carcinomas (HCCs). Expression of CD40 mRNA in 6 established HCC cell lines was analyzed by reverse-transcription polymerase chain reaction (RT-PCR) and CD40 expression on cell surface was examined by flow cytometrical analysis. We also examined the expression of CD40 in human HCC tissues (45 cases) and nontumor liver tissues (30 cases) by immunohistochemistry. To examine the function of CD40 in HCC cells, we investigated the effect of CD40 signaling on anti-Fas antibody and TNF-alpha-induced apoptosis in HepG2 cells. In addition, intracellular levels of cysteine protease P32 (CPP32) protein in HepG2 cells were also determined by Western blotting. We have shown that 6 HCC cell lines constitutively expressed CD40 mRNA and membrane-bound CD40 antigen, which was slightly up-regulated by interferon gamma (IFN-gamma). In addition, 60% of human HCC tissues demonstrated positive staining for CD40, whereas nontumor tissues showed little detectable staining. In HepG2 cells, CD40 stimulation does not affect cell viability, but significantly inhibited Fas and TNFR-mediated apoptosis in a dose-dependent manner by blocking the activation of CPP32. From these results, we conclude that CD40 expression in HCCs plays an important role in tumor biology, especially the resistance against Fas and TNFR-mediated apoptosis.

Apoptosis↗

PubMed1999

Spontaneous rupture of the urinary bladder is not a rare complication of radiotherapy for cervical cancer: report of six cases.

BACKGROUND: Spontaneous intraperitoneal rupture of the urinary bladder is an extremely rare event. It has been reported to be a rare complication of radiation therapy for cervical cancer, but no studies have ever reported the incidence of this life-threatening complication. MATERIALS AND METHODS: From August 1981 through December 1988, 143 patients with carcinoma of the uterine cervix were treated with high-dose-rate intracavitary brachytherapy combined with external beam therapy at Kobe City General Hospital. RESULTS: Of these patients, three (2.1%) suffered spontaneous intraperitoneal rupture of the urinary bladder as a late complication of radiation therapy between August 1995 and February 1998. Three other patients, treated with radiation therapy for cervical cancer at other hospitals, were also admitted to our hospital with this complication between August 1995 and February 1998. All six patients underwent laparotomy and repair of the perforation. However, rerupture of the bladder occurred in three of these patients. CONCLUSION: Spontaneous intraperitoneal rupture of the urinary bladder after radiation therapy for cervical cancer is less rare than previously expected, and urologists must consider the possibility of occurrence of this life-threatening event following radiation therapy.

Aged↗

PubMed1999

Anterior cruciate ligament reconstruction and physiological joint laxity: earliest changes in joint stability and stiffness after reconstruction.

Physiological joint laxity is an important element of normal knee joint function, providing smooth joint movement. However, the objective evaluation of post-operative results after knee ligament surgery is usually based primarily on stability and range of motion, and joint laxity has been ignored. In this study, we measured the joint stiffness of 82 knees undergoing anterior cruciate ligament (ACL) reconstruction with the Leeds-Keio artificial ligament, before the operation, immediately after the operation, and finally when the full range of motion was achieved postoperatively; changes in joint laxity after the ACL reconstruction were investigated. Before the operation, joint laxity was greater than that of the normal side (P < 0.01), but immediately after the operation it diminished compared not only with that observed preoperatively, but also with that of the normal side. When the full range of motion was achieved, joint laxity was lower than that observed immediately after the operation (P < 0.01), but still remained higher than that of the normal side (P < 0.01). In other words, stability was achieved, but joint laxity was diminished through the operation. In this series, a stiffer artificial ligament than the natural ACL was used, and maximum tension was applied during the operation, aiming at better stability, but this may cause diminution of joint laxity.

Adolescent↗

PubMed1999

Levels of chondroitin sulfate isomers in synovial fluid of patients with hip osteoarthritis.

We determined the levels of chondroitin sulfate (CS) isomers in the synovial fluid of patients with hip osteoarthritis (OA) to investigate their significance as markers reflecting extracellular matrix metabolism in joint tissues. A cross-sectional study of synovial fluid aspirated from 50 hip joints of 50 patients with OA was performed. Concentrations of chondroitin-4-sulfate (C4S) and chondroitin-6-sulfate (C6S) were determined by high-performance liquid chromatography. Levels of each marker molecule were investigated in relation to age and radiological stage of the disease. In all disease stages, the dominant CS isomer in synovial fluid was C6S. There was a significant negative correlation between levels of C6S and age. A significant inverse correlation was also observed between the ratio of C6S to C4S and age. Results of analysis of covariance in which age was covariate showed that the ratio of C6S to C4S in advanced and terminal stage OA was lower than that in early stage OA. The present results indicate that the ratio of CS isomers in synovial fluid in hip OA varies with the severity of disease. These molecules in synovial fluid may serve as a useful marker reflecting extracellular matrix metabolism in OA.

Adult↗

PubMed1999

Serum C-reactive protein level and the impact of cytoreductive surgery in patients with metastatic renal cell carcinoma.

PURPOSE: The prognosis of metastatic renal cell carcinoma is extremely poor. In this type of metastatic tumor cytoreductive surgery of the primary tumor is often performed to confirm the histological type or improve the response to immunotherapy with agents such as interferon or interleukin-2. However, the timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We determined the type of metastatic renal cell carcinoma for which cytoreductive surgery is beneficial. MATERIALS AND METHODS: We retrospectively reviewed the records of 58 patients in whom metastatic renal cell carcinoma was diagnosed at our hospital between 1986 and 1997. Three patients were excluded from study because they were judged to be poor candidates for surgery due to poor performance status. Of the remaining 55 patients 34 consented to cytoreductive surgery of the primary tumor and 21 did not. All except 1 patient were treated with interferon therapy. We evaluated the association of pretreatment serum C-reactive protein and the effect of surgery. RESULTS: We noted no significant difference in age at diagnosis, pretreatment serum immunosuppressive acidic protein, site of metastasis or performance status in 34 patients who underwent cytoreductive surgery and 21 who did not. Of the 21 patients in whom pretreatment serum C-reactive protein was within normal limits (less than 1.0 ng./ml.) no significant difference in disease specific survival was observed in those who did and did not undergo surgery (p = 0.4133). On the other hand, of 34 patients in whom pretreatment serum C-reactive protein was elevated (1.0 ng./ml. or greater) the prognosis was significantly better in those who did versus those who did not undergo surgery (p = 0.0054). Particularly the prognosis in patients in whom postoperative nadir C-reactive protein decreased to within normal limits was markedly better than in those in whom it remained elevated (p = 0.0025). CONCLUSIONS: Our study suggests that cytoreductive surgery is beneficial to patients in whom pretreatment serum C-reactive protein is elevated. Particularly, those in whom serum C-reactive protein decreases to within normal limits may expect longer survival when surgery is combined with postoperative immunotherapy. Currently to our knowledge the prognostic factor that predicts postoperative nadir C-reactive protein has not been identified, indicating that cytoreductive surgery of the primary tumor should be performed in patients with elevated pretreatment C-reactive protein and as performance status permits.

Aged↗

PubMed1999

A case of female large urethral diverticulum treated by electrofulguration.

Female urethral diverticulum is not an uncommon disease. We report a case of female urethral diverticulum which caused severe urethral pain, but for which the diagnosis had not been obtained at many hospitals for many years. Transurethral electrocauterization of the diverticulum was very effective in this case.

Diverticulum↗

PubMed1999

A case of tuberculosis of the prostate.

Tuberculosis of the prostate is uncommon. However, the number of patients with tuberculosis has once again recently been gradually increasing in Japan. The number of immunocompromised hosts, such as those with AIDS, is also increasing, suggesting that this rare infectious disease may increase in frequency in the near future. We present a case of tuberculosis of the prostate.

Abscess↗

PubMed1999

The role of volume-weighted mean nuclear volume in predicting disease outcome in patients with prostate cancer treated with radical prostatectomy.

BACKGROUND: Estimates of volume-weighted mean nuclear volume (MNV) are the only means by which unbiased estimates of three-dimensional parameters can be obtained from single two-dimensional sections without any assumptions. We have reported that for prostate cancer estimates of MNV are prognostically equal or superior to morphological grading of malignancy, such as Gleason score (GS), and in particular, that MNV proved to be a meaningful predictor of prognosis for patients with clinically localized tumors. However, all previous studies were conducted on patients treated conservatively, and no authors have tested whether estimates of MNV can predict the prognosis of patients treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective prognostic study of 52 patients with clinically localized prostate cancer diagnosed at three Hospitals in Shizuoka Prefecture, Japan (Shizuoka City Hospital, Shizuoka Prefectural Hospital and Shimada Municipal Hospital) and treated by radical prostatectomy was performed. Twenty of these patients were treated with hormone therapy before radical prostatectomy. Unbiased estimates of MNV were compared with clinical stage, histological grading according to GS and neo-adjuvant hormone therapy with regard to the prognostic value. RESULTS: MNV was significantly correlated with pathological T stage, but was not significantly correlated with the presence or absence of lymph node metastasis. Univariate analysis revealed that MNV correlated significantly with progression-free survival (p = 0.0116). Multivariate analysis revealed that MNV (p = 0.0115) and GS (p = 0.0275) were two significant independent predictors of progression-free survival. CONCLUSIONS: The results of the present study suggest that MNV and GS are powerful independent predictors of prognosis for prostate cancer treated with radical prostatectomy. We recommend estimates of MNV as a supportive method to the histological grading for patients with prostate cancer.

Antineoplastic Agents↗

PubMed1999

The role of volume-weighted mean nuclear volume in predicting disease outcome in patients with stage M1 prostate cancer.

BACKGROUND: Various factors have been reported to be of value in predicting the prognosis of prostate cancer. Gleason score (GS) and prostate-specific antigen (PSA) are the two most powerful prognosticators among them. We previously reported that estimation of volume-weighted mean nuclear volume (MNV) was a more useful prognosticator for prostate cancer than subjective histologic grading. In this study, we compared estimates of MNV with PSA and GS for predicting the prognosis of stage M1 prostate cancer. EXPERIMENTAL DESIGN: A retrospective prognostic study of 66 patients with stage M1 prostate cancer diagnosed between January 1989 and December 1996 at Shizuoka City Hospital and Shizuoka Prefectural Hospital was performed. The prognostic value of unbiased estimates of MNV were compared with PSA and histologic grading according to GS. RESULTS: Univariate analysis revealed that estimates of MNV (p=0.0136) and post-treatment nadir PSA level (p<0.0001) correlated significantly with the prognosis of stage M1 prostate cancer, whilst GS (p=0.9377), pre-treatment PSA level (p=0.7377) and rate of decrease in PSA level within 1 month after the beginning of therapy (p=0.8999) had no prognostic value. Multivariate analysis revealed that post-treatment PSA level and estimates of MNV were the two most powerful prognosticators. CONCLUSIONS: This study indicates that estimation of MNV is an important prognosticator, in conjunction with post-treatment nadir PSA level, in stage M1 prostate cancer.

Aged↗

PubMed1999

Dose estimations of fast neutrons from a nuclear reactor by micronuclear yields in onion seedlings.

Irradiations of onion seedlings with fission neutrons from bare, Pb-moderated, and Fe-moderated 252Cf sources induced micronuclei in the root-tip cells at similar rates. The rate per cGy averaged for the three sources, , was 19 times higher than rate induced by 60Co gamma-rays. When neutron doses, Dn, were estimated from frequencies of micronuclei induced in onion seedlings after exposure to neutron-gamma mixed radiation from a 1 W nuclear reactor, using the reciprocal of as conversion factor, resulting Dn values agreed within 10% with doses measured with paired ionizing chambers. This excellent agreement was achieved by the high sensitivity of the onion system to fast neutrons relative to gamma-rays and the high contribution of fast neutrons to the total dose of mixed radiation in the reactor's field.

Fast Neutrons↗

PubMed1999

Extensive post-traumatic ossification of the patellar tendon. A report of two cases.

Two men, aged 21 and 50 years, were seen with ossification of the patellar tendon after injury to the knee in adolescence. They complained of pain and had patella alta. Large bony masses were excised from below the affected patellae. The patellar tendon was then reconstructed using a Leeds-Keio ligament. The results at six and ten years, respectively, were good, with neither patient having pain or an extension lag.

Adult↗

PubMed1999

Osseointegration around titanium screws placed into the areas between guided bone augmented sites compared with osseointegration around guided bone graft augmented sites in rabbit tibia.

The aim of this study was to compare the degree of osseointegration around titanium screws placed into the areas between guided bone augmented sites and guided bone graft augmented sites in 8 Japanese white rabbit tibia. The skin and periosteum were incised and lifted to expose the inner surfaces of both tibia. Eight rabbits were divided into 2 groups: 1) a guided bone augmentation (GBA) group of 2 rabbits, and 2) a guided bone graft augmentation (GBCA) group of 6 rabbits. In the GBA group, the bone marrow was penetrated several times in both tibial bones. Three titanium screws were inserted into the bone so that the top of each screw was 3 mm above the bone surface and covered with an expanded polytetrafluoroethylene membrane (ePTFE). In the GBGA group autogenous cortical bone (10 mm x 10 mm x 1 mm) was taken from the left tibia and grafted on the inner surface of the right tibial bone, titanium screws being similarly inserted. The surgical site was covered by ePTFE. After healing for 2 months, the animals were euthanatized, and the experimental area was prepared for histological investigation. New bone had formed on the surgical sites in the GBA group and grafted bone had survived in the GBGA group, with no sign of infection or membrane exposure. The degree of osseointegration around the screw was 67.6 +/- 11.2% (mean +/- SD) in the GBA group and 78.8 +/- 11.9% in the GBGA group. There was no significant difference between the groups (p = 0.29). The ratio of mineralized bone to bone marrow was 45.7 +/- 6.2% in the GBA group and 64.4 +/- 4.4% in the GBGA group. There was a significant difference between the groups (p < 0.05). Although there was no significant difference for osseointegration around the screw placed into the GBA and GBGA sites, the quality of newly generated bone or grafted bone was quite different. Therefore, we suggest that predictable bone augmentation beyond the bone surface can be achieved by either the GBA or the GBGA procedure with ePTFE. However, it was difficult to conclude which procedure was superior with respect to the osseointegration around the titanium screw.

Animals↗

PubMed1999

[Retroperitoneal schwannoma: a case report].

A 67-year-old man was admitted for a complaint of lumbago. The patient had had the three operations for the schwannoma in spinal cord at the Neurosurgical Department of our hospital. Magnetic resonance imaging (MRI) revealed a right infrarenal tumor by chance. The tumor compressed the right kidney and measured 6 x 5 cm in size. On the tentative diagnosis of the retroperitoneal tumor, the patient was referred to the department of urology in our hospital and the tumor was excised. The histological diagnosis of the removed retroperitoneal tumor was schwannoma, and was thought to be heterotopic recurrent schwannoma.

Aged↗

PubMed1999

Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses cartilage destruction in rabbit experimental osteoarthritis.

OBJECTIVE: To investigate the in vitro effects of 6,7-dihydroxycoumarin (esculetin) on the production of matrix metalloproteinases (MMP) in rabbit articular cartilage, and the in vivo effects of orally administered CPA-926, a prodrug of esculetin, on cartilage destruction in rabbit experimental osteoarthritis (OA). METHODS: In vitro studies were performed using rabbit articular cartilage explants. Esculetin 10-100 microM was added to cartilage explants in the presence or absence of interleukin 1alpha (IL-1alpha). Effects of esculetin on cartilage metabolism were assessed. Proteoglycan release into medium was determined by dye precipitation with 1,9-dimethylmethylene blue, synthesis of proMMP-1 (interstitial procollagenase) and proMMP-3 (prostromelysin 1) by Western blotting, and collagen degradation activity using FITC labeled collagen. In vivo experimental OA was induced in the knee joints of 15 Japanese adult white rabbits by partial lateral meniscectomy. Ten rabbits were orally administered 200 or 400 mg/kg/day of CPA-926 from the day of surgery for 14 days. The size of the macroscopic erosive area on the femoral condyle and tibial plateau was measured, and cartilage destruction was histologically evaluated. Collagenolytic activities in synovial fluid were measured using FITC labeled collagen as a substrate. RESULTS: In vitro, esculetin inhibited the IL-1alpha induced release of proteoglycan into the medium in a dose dependent manner. The collagenolytic activities in cartilage explant medium induced by IL-1alpha were also suppressed with the addition of 33-100 microM esculetin (p = 0.0209 at 33 and 100 microM, p = 0.0202 at 66 microM). Western blotting of cartilage explant medium showed a decrease in the levels of proMMP-1 and proMMP-3 in the medium by treatment with esculetin. In vivo: At 14 days after surgery, the femoral condyle and tibial plateau in the control group showed macroscopic erosions of cartilage. Compared with the control group, the rabbits treated with CPA-926 at the dose of 400 mg/kg exhibited reduction of the size of the erosive area on the tibial plateau (p = 0.009). Histological evaluation indicated protection against the development of destructive changes in the tibial plateau cartilage at a dose of 200 mg/kg (p = 0.0442) and 400 mg/kg (p = 0.0446) of CPA-926. CONCLUSION: These results indicate that esculetin inhibits matrix degradation in rabbit joint cartilage explants through the suppression of MMP synthesis, secretion, or activity. Prophylactic administration of its prodrug, CPA-926, appears to provide some protection against cartilage destruction in a short term rabbit experimental OA model.

Administration, Oral↗

PubMed1999

Volume-weighted mean nuclear volume as a prognostic factor in renal cell carcinoma.

Volume-weighted mean nuclear volume (MNV) has been reported to have important prognostic value in many cancers. We investigated the prognostic value of MNV in patients with renal cell carcinoma (RCC). A retrospective study of the 155 patients with RCC treated by radical nephrectomy between 1976 and 1996 was conducted. MNV was evaluated in the surgical specimens using a stereologic technique. Univariate analyses by the log-rank test and then a multivariate analysis by the Cox proportional hazards model were performed to analyze the prognostic value of histopathologic parameters such as Robson stage, tumor-node-metastasis (TNM) classification, tumor grade, and MNV. There were significant correlations between MNV and Robson stage, TNM classification and tumor grade. Robson stage, TNM classification, tumor grade, and MNV were correlated significantly with disease-specific survival of RCC patients. There was no significant difference in disease-specific survival between patients with Grade 1 and Grade 2 tumors (94.8% of all patients), but MNV could predict the clinical outcome of these groups. MNV also was correlated significantly with disease-specific survival at all tumor stages. Multivariate analysis showed pT classification, M classification, tumor grade, and MNV to be independently associated with survival. These studies strongly suggest that MNV may provide new and useful information to accurately predict the prognosis of patients with RCC.

Adult↗

PubMed1999

[Combined treatment with CDDP and radiation effective against neuroendocrine carcinoma of the urinary bladder: a case report].

A case of neuroendocrine carcinoma (small cell carcinoma) of the urinary bladder is presented. A 76-year-old man complaining of dysuria visited our clinic on October 31, 1997. On physical examination, a huge mass was palpable in the lower abdomen. Abdominal and pelvic computed tomographic (CT) scan revealed a huge mass, 6.7 x 6.0 cm in size, with extravesical extension in the anterior wall of the urinary bladder and no metastatic lesions. Percutaneous biopsy of the tumor revealed undifferentiated neuroendocrine carcinoma. The value of serum neuron specific enolase (NSE) was 220 ng/ml (normal range: 0-10 ng/ml). Twenty days after the first CT scan, the tumor had grown to be 12.5 x 11.0 cm in size. He was treated with combination therapy of systemic cisplatin and external pelvic radiation and then achieved complete remission on CT scan and biopsy. The value of serum NSE was normalized. Four months later, abdominal CT scan revealed a huge metastastic lesion in the paraaortic and parahepatic regions, but, no local recurrence in the bladder. The value of serum NSE was 240 ng/ml. He was treated with 4 cycles of systemic combination therapy of cisplatin and etoposide. He achieved partial remission (regression rate: 77%) on CT scan after completion of the first 2 cycles, but the tumor showed rapid re-growth and he died of cancer 1 month later despite another 2 cycles. These combination therapies were effective against neuroendocrine carcinoma of the urinary bladder, although, the duration of the effect was short.

Aged↗