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H Koga

Publications and source records attributed to H Koga.

At least 91 records · Page 5Linked to original sources
PubMed1999

Mechanisms of drug resistance in chemotherapy for urogenital carcinoma.

Cancer chemotherapy is the principal approach for urogenital cancers. However, the acquisition of resistance to anticancer agents is a critical factor that limits the successful treatment of malignancies. The multidrug resistant (MDR) phenotype has been widely recognized in cancer chemotherapy in urogenital tumors and the mechanisms underlying MDR have also been extensively studied. One of the principle mechanisms in MDR is caused by the overexpression of P-glycoprotein (P-gp), encoded by the multidrug resistance gene (MDR1). It functions as an ATP-dependent active efflux pump of chemotherapeutic agents in human cancer cells. Recently, other drug resistance proteins, including multidrug resistance-associated protein (MRP1) and cMOAT (or MRP2), were also identified from multidrug resistant cells. A functional analysis of MRP1 has shown that MRP1 may have the potential to act as a transporter of glutathione conjugates, which has been known as a central detoxification pathway in anticancer agents. Furthermore, several other resistance-related proteins (e.g. glutathione S-transferase, metallothionein, thioredoxin, topoisomerase I, II, O6-alkylguanine-DNA methyltransferase, etc.) have been found to be up- or down-regulated in resistant cells and these molecules are believed to contribute to the resistant phenotype as well. Based on the molecular characteristics identified in MDR, several experimental and clinical approaches have been studied to overcome MDR. One of these strategies is to reverse MDR by using such P-gp inhibitors as verapamil and cyclosporine A. In this review, we summarize the recent advances in MDR-related molecules and clinical trials to circumvent MDR in urogenital carcinomas.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Necessity of repeat biopsies in men for suspected prostate cancer.

BACKGROUND: The indications for repeat prostate needle biopsy in men whose initial biopsy results revealed no evidence of cancer are not defined. METHODS: We retrospectively studied 218 consecutive cases of men undergoing prostate biopsies for suspected cancer. Men in whom cancer was found on repeat biopsy were compared with others with regard to age, digital rectal examination, serum prostate-specific antigen (PSA) concentration, prostate volume, PSA density, PSA slope and the frequency of prostatic intraepithelial neoplasia (PIN) on initial prostate biopsy. RESULTS: Of the 114 cancers detected, 99 (87%) were diagnosed on initial biopsy and 15 (131%) were diagnosed on repeat biopsy. Mean PSA concentration and mean PSA density were significantly higher in patients with cancer on initial biopsy than on repeat biopsy (P<0.05), but they were similar among patients with and without cancer on repeat biopsy. The PSA slope showed a more progressive increase in patients with cancer on repeat biopsy than in those patients without cancer at 6 month intervals. Of the 218 patients undergoing prostate biopsy, seven (3.2%)) were identified with high grade PIN but without concurrent prostate cancer. Prostate cancers were detected in two of these seven patients (29%) on repeat biopsy. CONCLUSIONS: Serum PSA levels and PSA density did not provide useful predictive information about the indications of repeat biopsy. We conclude that men with a more progressive increase in PSA levels at 6 months intervals and high grade PIN on prostate needle biopsy should undergo repeat sampling to exclude missed cancer.

Aged↗
PubMed1999

The relationship between prognosis and CEA-dt after hepatic resection in patients with colorectal carcinomas.

AIMS: CEA-doubling time (CEA-dt) was calculated by measuring serum CEA at two voluntary points. As CEA-dt is correlated with tumour doubling time the growth rate of liver metastasis could be determined. We investigated the relationship between CEA-dt and prognosis to determine the indications for resection of liver metastasis. METHODS: We examined 334 patients diagnosed with resected liver metastasis of colorectal carcinoma. Patients were divided into three categories based on CEA-dt; Group A, CEA-dt <30 days; Group B, 30 days </=cCEA-dt <80 days; and Group C, CEA-dt >/=s80 days. Clinicopathological parameters, the 3-year or 5-year survival rate and the rate of recurrence were compared among the three groups. RESULTS: In Group A, the survival time after hepatic resection was significantly shorter compared to the other groups. Furthermore, multiple liver metastasis showed slightly reduced CEA-dt levels compared with solitary metastasis, but even in patients with solitary liver metastasis, the rate of survival was poor. In 70% of Group A patients, recurrent tumour was recognized within 1 year of hepatic resection. CONCLUSION: When surgery for liver metastasis of colorectal cancer is considered. Group A patients should be recognized as having a poor prognosis and a high rate of recurrence after hepatic resection, and CEA-dt should be employed as a prognostic factor.

Adult↗
PubMed1999

Detection of hepatitis-C virus and hepatitis-C virus replication in hepatocellular carcinoma by in situ hybridization.

BACKGROUND: Although hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma (HCC), the role of this virus in carcinogenesis is not fully understood. METHODS: We studied HCV infection and replication by detecting plus- and minus-strand HCV RNA by in situ hybridization (ISH) in surgically resected HCCs and adjacent non-cancerous tissue obtained from 15 anti-HCV antibody-positive patients with HCC. RESULTS: Plus-strand HCV RNA was found in 9 of 15 HCCs. Both plus- and minus-strand HCV RNA were detected in four of these nine patients. In non-cancerous tissues obtained adjacent to the HCC, plus-strand HCV RNA was found in 10 of 15 patients, whereas both plus- and minus-strand HCV RNA were detected in 7 of these 10 patients. The degree of staining by ISH did not correlate with the differentiation of the HCC, histologic classification of the non-cancerous tissue, serum HCV RNA levels, or serum transaminase levels. CONCLUSIONS: HCV can be found in and replicates in both hepatoma cells and in non-cancerous hepatocytes in anti-HCV antibody-positive patients with HCC. The direct effects of HCV viral gene products on normal hepatocytes in the development of HCC require additional study.

Aged↗
PubMed1999

Relationship between genetic alteration of the rpsL gene and streptomycin susceptibility of Mycobacterium tuberculosis in Japan.

We have investigated the effect of genetic alterations in the rpsL gene on the MICs of streptomycin for Mycobacterium tuberculosis strains. Direct DNA sequencing showed a point mutation in 23/121 strains; in 18 strains the mutation was associated with an amino acid change. The MICs of streptomycin in 22 out of 23 point-mutated strains were > or = 256 mg/L. Restriction fragment length polymorphism (RFLP) analysis showed mutations at codon 43 in all 18 strains with point mutations in the same codon. Our results suggest that both RFLP and base sequencing analysis of the rpsL gene are useful for the rapid prediction of highly streptomycin-resistant strains of M. tuberculosis.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1999

Obesity, weight gain and risk of colon adenomas in Japanese men.

Obesity has been related to increased risk of colon cancer or adenomas, but the epidemiologic findings are not entirely consistent. We examined the relation of not only body mass index (BMI) but also waist-to-hip ratio (WHR) and weight gain to colon adenoma risk in men who received a preretirement health examination at the Japan Self Defense Forces (SDF) Fukuoka and Kumamoto Hospitals during the period from 1995 to 1996. In the series of 803 men at age 47-55 years, 189 cases of colon adenomas and 226 controls with normal total colonoscopy were identified. Weight at 10 years before was ascertained by referring to the recorded data. After allowance for hospital, rank in the SDF, smoking and alcohol use, weight gain over the past 10 years was significantly associated with increased risk of colon adenomas (odds ratio for > or = 6 kg versus < or =-2 kg = 2.2; 95% confidence interval 1.0-4.8). High BMI and high WHR were each associated with increased risk, but only WHR was related to the risk independently of weight gain. In particular, weight gain accompanied with a high WHR was associated with a significant increase in the risk. Men with high physical activity tended to have lower risk. Associations with obesity-related variables and physical activity were not materially differential as regards the location and size of adenoma. The findings indicate that weight gain in middle age leading to abdominal obesity increases the risk of colon adenomas, and consequently of colon cancer.

Adenoma↗
PubMed1999

[Case of varicella-zoster pneumonia with bronchioalveolar lavage confirmed by the detection of VZV DNA in the bronchial washing by the polymerase chain reaction].

A 32-year old male was admitted to our hospital complaining of cough, fever, and skin eruptions. He was coctacted with a child who had chickenpox 3 weeks before the onset. He showed the elevating of antibody to varicella-zoster virus. Despite of the administration of Acyclovir for four days, cough was not relieved and a chest X-ray film showed infiltrative shadow in right middle lobe of the lung. Bronchoscopic examination revealed vasicle and edema, and the varicella-zoster virus (VZV) DNA was detected in the bronchoalveolar lavage by the polymerase chain reaction. The patient in first case confirmed by the virus DNA in the bronchial washing by the PCR.

Adult↗
PubMed1999

Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects.

The aim was to identify potentially treatable risk factors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living in the community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physical and neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma amino acid measurements. Brain MRI infarcts, deep white matter lesions (DWMLs), and periventricular hyperintensities were found in 26%, 43%, and 29% of the 178 participants, respectively. Subjects with DWMLs were significantly older and had a higher frequency of hypertension, higher systolic blood pressure, and more brain infarcts, but lower plasma concentrations of tryptophan. In the multivariate model, greater age and lower plasma tryptophan concentrations were independently associated with DWMLs. Tryptophan concentrations were inversely related to DWML grading, whereas hypertension and brain infarction were more common in subjects with higher extents of DWMLs. The present study suggests that greater age and lower plasma tryptophan concentrations were important in producing DWMLs in elderly subjects.

Aged↗
PubMed1999

Experimental enteropathy in athymic and euthymic rats: synergistic role of lipopolysaccharide and indomethacin.

The aim of this study was to investigate the immunologic and microbiological bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen-free (SPF) rats were reared under conventional or SPF conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously described ulcer index and tissue myeloperoxidase activity. Both euthymic and athymic nude rats developed intestinal ulcers to the same degree under conventional conditions but no or minimal ulcer under SPF conditions. Pretreatment of conventional rats with intragastric kanamycin sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a dose-dependent fashion. Interestingly, when lipopolysaccharide was injected intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in these rats in a dose-dependent manner. We confirmed that kanamycin decreased the number of gram-negative bacteria and endotoxin concentration of the small intestine in a dose-dependent fashion. These results indicate that indomethacin enteropathy is bacteria dependent and does not require a T cell function. Synergy between indomethacin and bacterial lipopolysaccharide may play a major role in this enteropathy.

Animals↗
PubMed1999

Human retinoic X receptor beta: complete genomic sequence and mutation search for ossification of posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the ligament. OPLL is a very common disorder, in fact it constitutes the leading cause of myelopathy among Japanese. In the previous report, we provided the genetic linkage evidence that the genetic susceptibility of OPLL mapped to HLA complex of chromosome 6. As a candidate gene approach, retinoic X receptor beta (RXR beta), assigned to chromosome 6p21.3 adjacent to HLA class II, was analyzed for a possible causality. To start screening for the molecular variants of RXR beta in OPLL subjects, we first obtained P1 phage genomic clones containing the entire human RXR beta and elucidated the genomic organization of the gene. The human RXR beta is composed of 10 exons spanning over 6.2 kb of genomic DNA. Sequence analysis of the promoter region revealed a GC-rich sequence without TATA motif. We have identified three distinct molecular variants, one was in exon 10 and two were in the intergenic region between RXR beta and collagen 11A2 (COL11A2). Two variants in the intergenic region, 3' end + 140 and 3' end + 561, exhibit statistically significant associations with OPLL in case-control study (p = 0.0028 for 3' end + 140 and p = 0.034 for 3' end + 561). These results indicate that the genetic causality of OPLL lies within or close to the RXR beta/COL11A2 locus.

Adult↗
PubMed1999

Pulse intravenous cyclophosphamide treatment for steroid-resistant interstitial pneumonitis associated with polymyositis.

Interstitial pneumonitis (IP) is a serious complication in polymyositis/dermatomyositis (PM/DM), leading to significant morbidity or mortality. Here, we report the successful treatment by pulse intravenous administration of cyclophosphamide in the early course of lung involvement in PM, and with subsequent low-dosage oral administration of azathioprine in a patient with steroid-resistant IP associated with PM/DM. Although the precise pharmacological mechanism induced by cyclophosphamide in this disease remains unclear, such a cytotoxic drug raises the possibility of control of steroid-resistant PM/DM-associated IP when used in the early course of IP.

Adult↗
PubMed1999

Bronchial amyloidosis successfully treated with low-dose long-term erythromycin therapy.

A 69-year-old man was admitted for evaluation of an abnormal chest X-ray. A diagnosis of primary bronchial amyloidosis was made on the basis of the chest X-ray, CT scans and bronchial biopsy specimens. The patient was treated with low-dose long-term erythromycin therapy (600 mg/day). After four months of therapy, chest CT scans, bronchoscopic findings and bronchial biopsy specimens revealed significant improvement of inflammatory changes. Low-dose erythromycin therapy may be helpful in terms of its anti-inflammatory effects for patients with bronchial amyloidosis.

Aged↗
PubMed1999

[Clinicopathological analysis of transition zone cancer of the prostate: the clinical significance of coexistent non-transition zone cancer foci].

BACKGROUND: Dominant cancer of transition zone origin of the prostate (TZ cancer) has been frequently detected, because ultrasound-guided systematic biopsies have been generalized. In cases of TZ cancer, we attempted to determine clinical significance of coexistent non-TZ cancer foci. MATERIALS AND METHODS: Twenty cases with TZ cancer who underwent radical prostatectomy or cystoprostatectomy were clinicopathologically evaluated using step-sectioned specimens. RESULTS: In TZ cancer foci, there were extraprostatic extension in 5 cases (25%), seminal vesicle invasion in 2 cases (10%), positive surgical margin in 6 cases (30%) and bladder neck invasion in 4 cases (20%). The extraprostatic extension and the positive surgical margin occurred at the anterior or anterioapical portion of the prostate in all the cases. On the other hand, 17 (85%) had coexistent non-TZ cancer foci. In non-TZ cancer foci, there were extraprostatic extension in 3 cases (15%), seminal vesicle invasion in 1 case (5%) and positive surgical margin in 1 case (5%). The extraprostatic extension and the positive surgical margin occurred at the posteriolateral portion of the prostate in all the cases. In 3 cases a coexistent non-TZ cancer focus showed the extraprostatic extension, the seminal vesicle invasion or the positive surgical margin, although a TZ cancer focus were organ-confined. CONCLUSION: We should add attention to coexistent non-TZ cancer foci in TZ cancer cases. Particularly, we believe that pre-operative evaluation of non-TZ cancer foci is needed in TZ cancer cases of the candidates for nerve-sparing radical prostatectomy.

Aged↗
PubMed1999

[Cauda equina syndrome due to recurrent malignant lymphoma of the spinal cord. A case report].

A 50-year-old man noticed a mass in the right cervical region and presented to our hospital. He underwent biopsy of a cervical lymph node, which revealed non-Hodgkin's lymphoma (diffuse large B cell, lymphoblastic type) histologically. He was treated with chemotherapy (CHOP) and radiation, and achieved complete remission. Two months later, he was admitted because of distal pain and extensive numbness of the lower limb as well as weakness of the left leg. Lumbar MRI showed an area of abnormal intensity in the cauda equina. Cytological examination of cerebrospinal fluid showed class V (lymphoma cells), so he was diagnosed as having recurrent malignant lymphoma of the spinal cord. He was treated with intrathecal chemotherapy and irradiation. After the treatment the mass in the cauda equina disappeared and the neurological symptoms in his legs resolved. It is rare for malignant lymphoma to recur in the spinal cord, particularly the cauda equina. It is well known that cauda equina syndrome can be caused by vertebral lesions and primary spinal cord tumors, but it is also necessary to keep malignant lymphoma of the cauda equina in mind.

Aged↗
PubMed1999

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males.

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

Alcohol Drinking↗
PubMed1998

Impairment of cell adhesion by expression of the mutant neurofibromatosis type 2 (NF2) genes which lack exons in the ERM-homology domain.

Neurofibromatosis 2 (NF2) is an inherited disorder characterized by a predisposition to multiple intracranial tumors. The protein encoded by the NF2 gene has striking similarities to ezrin, radixin and moesin (ERM) proteins which link membrane proteins to the cytoskeleton. Therefore, it can be speculated that the disruption of cytoskeletal organization by alterations in the NF2 gene is involved in the development of tumors. It has been reported that the majority of NF2 mutations were nonsense or frameshift mutations that result in premature termination of translation. To facilitate the detection of these mutations, we performed protein truncation test and found that 11 of 14 NF2 patients had truncational mutations (79%). Seven of the 11 patients (64%) had a splicing abnormality which lead to absence of exons in the ERM homology domain. To examine the biological significance of the exon-missing mutations in the ERM homology domain, we expressed the wild-type (wt-NF2) and the various mutant NF2s (mu-NF2s) in a fibroblast cell line by using both liposome-mediated transfection and nuclear microinjection of the expression plasmids. The wt-NF2 showed intense punctate staining in the perinuclear cytoplasm in addition to overall staining of the submembranous area, whereas the mu-NF2s lacking exons in the ERM homology domain showed granular staining at the perinuclear region without any accumulation at the submembrane region. Microinjection of wt-NF2 cDNA into the nucleus of VA13 cells revealed that wt-NF2 protein induced a progressive elongation of cell processes. Furthermore, cells that expressed mu-NF2 had decreased adhesion, which resulted in detachment from the substratum. These findings suggested that the exon-missing mutations in the ERM-homology domain may affect cell membrane-cytoskeleton signaling and consequently disrupt cell-to-cell or cell-to-matrix interaction.

Adolescent↗