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Biomedical subjects

K Sugimura

Publications and source records attributed to K Sugimura.

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

Clinical results of total cystectomy for 92 patients with bladder cancer.

The survival rate of 92 patients with primary bladder cancer who had undergone total cystectomy during a 13-year period from 1984 to 1996 was examined. The mean follow-up period was 1,886 days. The 5-year survival rate was 67.9% and the 10-year survival rate was 55.1%. When survival rates were compared pathohistologically, with 81 patients with transitional cell carcinoma divided into two groups, a high-stage group including T3 and T4 patients and a low-stage group with all other patients, the cancer-specific 5-year survival rate of the low-stage group was 88.9% while that of the high-stage group was 45.4%; this difference was significant (p = 0.0002). There were also significant differences in survival rate between those with and those without regional lymph node metastasis, those with and those without lymphatic infiltration, and those with and those without vascular infiltration. However, there was no significant difference in survival rate for the 34 patients with T3 or T4 disease when those with or without chemotherapy and/or radiation therapy were compared.

Adult↗
PubMed1998

T cell proliferation-augmenting activities of the gene 3 protein derived from a phage library clone with CD80-binding activity.

We have isolated a phage clone, F2, by panning a phage library with a CTLA4-conformation recognizing mAb (anti-CTLA4 mAb). The unique sequence of 15 amino acids with an internal disulfide bond was inserted in the gene 3 proteins of F2 phage clone (F2-g3p). We show here that 1) F2-g3p was recognized with anti-CTLA4 mAb but not with anti-CD28 mAb, and 2) F2-g3p bound to CD80 but not to CD86. The surface plasmon resonance analysis showed that F2-g3p strongly bound CD80. F2-g3p inhibited the binding of CTLA4 to CD80 but not to CD86. In contrast, F2-g3p weakly inhibited the binding of CD28 with CD80. When hen egg lysozyme (HEL)-primed lymph node cells were stimulated with HEL in the presence of F2-g3p in vitro, cell proliferation was highly potentiated. In the absence of antigenic stimulation, F2-g3p induced no T cell proliferation, indicating the costimulatory nature of F2-g3p. The T cell-augmenting activity of the F2 clone was eliminated when the F2 clone was preincubated with CD80-Ig before the addition to the cultures, indicating the involvement of CD80-binding in the F2-g3p-mediated immunopotentiation. Thus, the F2 motif conferred CD80-binding activity and an immunoregulatory function to the g3p.

Abatacept↗
PubMed1998

Alternative splicing of the mRNA coding for the human endothelial angiotensin-converting enzyme: a new mechanism for solubilization.

Angiotensin converting enzyme (ACE) is a zinc metalloprotease anchored in the plasma membrane with a carboxy-terminal hydrophobic domain. In addition, the existence of a soluble form of ACE lacking the transmembrane domain has been reported. We show evidence for the existence of an mRNA specific for this isoform produced by alternative splicing. In human umbilical vein endothelial cells, two ACE mRNAs of different length (4.3 and 3.5 kb) were detected by Northern blot. Ribonuclease protection assays and the sequence of a PCR-amplified cDNA fragment show that the shortened ACE mRNA lacks the exons coding for the transmembrane domain of the protein. As this mRNA could be the source of soluble ACE, plasma ACE activity may be regulated on the level of mRNA processing.

Alternative Splicing↗
PubMed1998

Non-invasive estimation of human left ventricular end-diastolic pressure.

Sato et al. (Electronic Letters 32, 949-950, 1996) reported that one can obtain a non-invasive estimate of left ventricular (LV) pressure at around end-diastole in an isolated canine preparation. In this study we examined whether this method can be applied to humans. Using the method proposed by Kanai et al. (IEEE. Trans. UFFC, 43, 791-810,1996), we detected small amplitude LV vibration from an ultrasonic pulse Doppler signal reflected from the interventricular septum in five patients (44-63 y.o., male;4, female;1). We measured the oscillation frequency of the LV wall through the wavelet transform of small amplitude LV vibration, and calculated LV pressure at around end-diastole from the values of oscillation frequency, internal radius and wall thickness using Mirsky's equation. The estimated LV pressures at around end-diastole were similar to end-diastolic pressure measured directly by cardiac catheterization. These results show the possibility that this method allows for the non-invasive estimate of LV pressure at around end-diastole, and furthermore provides the basis for future clinical applicability of this technique.

Adult↗
PubMed1998

Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.

Phage library clones selected by a conformational epitope-recognizing and inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand-like three-dimensional structure. This pseudoreceptor/ligand should be able to bind to natural ligand/receptor molecules. We tested this idea using anti-T cell costimulatory molecule antibodies and successfully isolated phage clones with costimulatory effects on T-cell proliferation. This strategy facilitates the designing of regulatory peptide molecules in the absence of precise information about the structure-function relationships in receptor/ligand interactions.

Abatacept↗
PubMed1998

In vivo gene transfer methods in the bladder without viral vectors.

OBJECTIVE: To examine three in vivo gene transfer methods, without viral vectors, for use in bladder cancer. MATERIALS AND METHODS: Three methods were selected: (i) haemagglutinating virus of Japan (HVJ)-liposomes possessing membrane fusion activity were intraluminally injected into rat bladders; (ii) using a particle gun, rabbit bladder mucosa was bombarded with DNA-coated gold microcarriers; (iii) electrotransfection was also assessed in rabbit bladder by pulsed direct currents (0.15-0.2 A, 50 ms, repeated eight times) generated between needle electrodes after the submucosal injection of DNA solution. The beta-galactosidase gene and chloramphenicol acetyl-transferase gene were used as marker genes to detect gene transfer. RESULTS: HVJ liposomes efficiently transfected superficial layers of urothelium, with a peak of expression on day 5. The particle gun produced a heterogeneous but efficient transfection in deeper layers of the urothelium. By electrotransfection, both submucosal interstitial cells and urothelium were transfected. No major complications occurred with these three methods. CONCLUSION: HVJ-liposomes are potentially useful for treating carcinoma in situ. With further refinement, the last two methods may be suitable for adjuvant therapy in treating localized bladder tumours.

Animals↗
PubMed1998

Enhanced angiotensin II stimulates renal disorders in transgenic Tsukuba hypertensive mice.

Tsukuba hypertensive mice (THMs) are transgenic mice carrying human renin-angiotensin system (RAS) genes. The aim of this study is to evaluate whether renal disorders are present in THMs. Twenty-week-old THMs and C57BL/6 mice (C57s) were used for this study. Each group consisted of 8 mice. Systolic blood pressure, urinary volume, water intake and urinary albumin excretion were measured in each mouse. Each mouse was then euthanized, and the renal glomerulosclerosis index and glomerular size were measured. Systolic blood pressure of THMs was about 40 mmHg higher than that of C57s. Urinary volume, water intake and urinary albumin excretion were significantly higher in THMs than in C57s. The renal glomerulosclerosis index and glomerular size were also significantly higher in THMs than in C57s. These results suggested that an enhanced renin-angiotensin system, including its hypertensive effects, stimulates albuminuria, renal glomerulosclerosis and glomerular hypertrophy in THMs.

Angiotensin II↗
PubMed1998

Assessment of cell cycle-related elements p53, p21WAF1/Cip1, cyclin D1 and PCNA in a mixed transitional cell carcinoma and adenocarcinoma of the renal pelvis: a case report.

A case featuring a well differentiated adenocarcinoma mixed with a transitional cell carcinoma (TCC) arising in the renal pelvis of a 63-year-old woman is presented. Daughter tumors, located in the ureter and the uretero-vesical junction, were entirely TCC in character. Immunohistochemical assessment of cell cycle-related proteins revealed overexpression of cyclin D1 but reduced p21WAF1/Cip1 or PCNA expression in the adenocarcinomatous regions. Conversely, expression of p21WAF1/Cip1 and PCNA was high in the TCC components. Immunohistochemical staining for p53 was negative and PCR-SSCP analyses confirmed the absence of any mutation. Therefore, assessments on the altered expression of cell cycle-related elements may contribute to our understanding of tumor biology in adenocarcinomas and TCCs of the renal pelvis and to identifying the similarities and differences between the two different cell types.

Adenocarcinoma↗
PubMed1998

Tissue-localized angiotensin II enhances cardiac and renal disorders in Tsukuba hypertensive mice.

OBJECTIVE: To evaluate the relation of tissue-localized angiotensin II (Ang II) concentration with cardiac hypertrophy and glomerulosclerosis in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. DESIGN: Thirty THM aged 12 weeks were distributed equally to a lisinopril dosage group, a hydralazine dosage group, and an untreated group. Ten age-matched C57BL/6 mice were used as normal controls. Administration was performed for 8 weeks from 12 weeks of age. All mice were euthanized at 20 week of age, and the heart-to-body weight ratio, the renal glomerulosclerosis score, tissue Ang II concentration and tissue catecholamine concentration were measured. RESULTS: In the untreated group, a significant increase in every examination item was found as compared with that in C57BL/6 mice. In the lisinopril group, the observed value of every item was significantly lower than that in the untreated group. In the hydralazine group, tissue Ang II and catecholamine concentrations and the heart-to-body weight ratio were not different from those in the untreated group. Although the glomerulosclerosis score in the hydralazine group was significantly less than that in the untreated group, this was significantly higher than that in the lisinopril group. CONCLUSION: Tissue Ang II concentration is more important than hypertension in causing cardiac hypertrophy, and both tissue Ang II level and hypertension are important in causing glomerulosclerosis in THM.

Angiotensin II↗
PubMed1998

Role of the transition zone for elevating serum prostate-specific antigen in benign prostatic hyperplasia.

BACKGROUND: Patients with benign prostatic hyperplasia (BPH) have a wide range of concentrations of PSA. However, it is not known what factors influence the concentration of serum PSA other than the prostate volume. BPH is composed of an enlarged transition zone (TZ) and other zones (nonTZ). The TZ is thought to play a more important role than the nonTZ in determining the concentration of serum PSA in BPH patients. METHODS: We investigated the individual glandular zone volume, the amount of PSA produced by each zone and the PSA density in each zone in 23 patients with histologically-confirmed BPH. The PSA density in the TZ was calculated by dividing the difference between the serum PSA before and after surgical resection by the specimen weight. We examined the influence of these parameters on the concentration of serum PSA in BPH patients. RESULTS: The serum PSA concentration correlated with the amount of PSA produced by the TZ (r=0.90, P< 0.0 1), but not the nonTZ (r=0.25, P=0.29). The concentration of serum PSA also showed a significant correlation with the TZ volume (r=0.67, P< 0.01) and the PSA density in the TZ (r=0.51, P< 0.05), but not with the PSA density in the nonTZ (r=-0.06, P=0.81). Also, age was inversely correlated with the PSA density in the TZ (r=-0.69, P< 0.01). CONCLUSION: The hypertrophic prostate cell volume (TZ volume) and activity (PSA density in the TZ) significantly correlated with the concentration of serum PSA in BPH patients, and the TZ cell activity decreased inversely with age in these BPH patients.

Age Factors↗
PubMed1998

Spectrum of cytokine gene expression in intestinal mucosal lesions of Crohn's disease and ulcerative colitis.

BACKGROUND/AIMS: We investigated the mRNA expression of spectrum of cytokines in the colonic mucosa in inflammatory bowel disease (IBD). METHODS: The expression of cytokine gene was evaluated by using the reverse transcription-polymerase chain reaction and the radioactivity of amplified cDNA standardized by coamplified beta-actin cDNA. RESULTS: Crohn's disease and ulcerative colitis showed significantly increased expression of IL-1beta, IL-6, IL-8 and TNF-alpha mRNA as compared with controls (p < 0.05). CONCLUSION: Proinflammatory cytokines such as IL-1beta, IL-6, IL-8 and TNF-alpha are closely involved in the immune abnormalities of inflammatory mucosal lesions in IBD.

Adolescent↗
PubMed1998

Inhibitory effects of a subdepressor dose of L-158,809, an angiotensin II type 1 receptor antagonist, on cardiac hypertrophy and nephropathy via the activated human renin-angiotensin system in double transgenic mice with hypertension.

The effects of L-158,809, an angiotensin II type 1 receptor antagonist, on cardiac hypertrophy and nephropathy were examined using Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. Nine male THM aged 20 weeks were assigned to each of a no-dosage group and an L-158,809 dosage group, and L-158,809 was administered for 8 weeks. Nine age-matched male C57BL/6 mice were used as normal control animals. At 28 weeks of age, all of the mice were euthanized. Systolic blood pressure, urinary volume, water intake volume, urinary albumin excretion, heart weight and kidney weight to body weight ratios and a glomerulosclerosis index were measured. In the no-dosage group, the values of all of these parameters were larger than those in the control mice. In the L-158,809 group, all of the parameters showed significant improvement, except for blood pressure, which was not significantly different from that in the no-dosage group. These results suggest that the renin-angiotensin system played a crucial role in the cardiac hypertrophy and nephropathy in THM, and that L-158,809 exhibited strong curative effects on cardiac hypertrophy and nephropathy by blocking the angiotensin II type 1 receptor.

Angiotensin Receptor Antagonists↗
PubMed1998

Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia.

Hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) is a common intermediate metabolite of cholesterol synthesis and ketone formation in the liver. In order to study the effect of HMG-CoA reductase inhibitor (pravastatin) on ketone formation, changes in the plasma levels of ketone bodies by treatment with pravastatin were studied in 18 non-insulin dependent diabetics with hypercholesterolemia. Body mass index, diabetic control, and plasma free fatty acid levels were not changed during the study, and the plasma levels of cholesterol decreased significantly from 250 +/- 25 to 211 +/- 34 mg/100 ml after 6 months of pravastatin treatment. The plasma levels of acetoacetic acid also significantly decreased from 37.7 +/- 22.6 to 28.4 +/- 13.4 mumol/l, and those of 3-hydroxybutyric acid and total ketone bodies also tended to decrease after pravastatin treatment. These results suggest that pravastatin decreases ketone formation in hepatic mitochondria besides cholesterol synthesis in hepatic microsome.

3-Hydroxybutyric Acid↗
PubMed1998

Significant role of the increase in renin-angiotensin system in cardiac hypertrophy and renal glomerular sclerosis in double transgenic tsukuba hypertensive mice carrying both human renin and angiotensinogen genes.

Tsukuba hypertensive mice (THM) are a hypertensive model prepared by mating a transgenic mice with human renin gene and a transgenic mice with human angiotensinogen gene. In the present study, we examined effects of renin-angiotensin system (RAS) on cardiac hypertrophy and renal disorders using Tsukuba hypertensive mice. While THM showed an increase of about 30 mmHg in systolic pressure compared to C57BL/6 mice employed as normal control animals, the increase in blood pressure was not observed in the mice to which either gene was transferred. Urinary volume, water intake volume, urinary albumin excretion, heart to body weight ratio and renal glomerular sclerosis index increased significantly in THM, but none of these parameters showed a significant difference from the C57 mice when they were examined in mice to which either of the genes was transferred. In contrast, when lisinopril was administered to THM, all the parameters decreased significantly without lowering the systolic pressure. From these findings, it was demonstrated that RAS was playing a significant role in cardiac hypertrophy and renal disorders of THM and that lisinopril had inhibitory effects on cardiac hypertrophy and renal glomerular sclerosis by inhibiting RAS.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

[Leiomyoma of the bladder: report of two cases].

We report 2 cases of leiomyoma of the urinary bladder. A 41-year-old female visited our hospital with the complaint of pollakisuria. A solid tumor of the urinary bladder was found by ultrasonography. A large shadow defect at the left-anterior wall was shown by drip infusion pyelography (DIP). Computed tomographic scan (CT) and magnetic resonance imaging (MRI) also revealed a large tumor. T1-weighted image revealed a homogeneous low intensity tumor and T2-weighted image disclosed heterogeneous low intensity tumor. Cystoscopy revealed a large submucosal tumor. Partial cystectomy was performed, and she has had neither recurrence nor metastasis for 36 months. A 32-year-old male was referred to our hospital with the complaint of macrohematuria. A solid tumor of the urinary bladder was found by ultrasonography. A shadow defect was not clearly detected by DIP. A large tumor was detected on the anterior wall by MRI. T1-weighted image showed a homogeneous low intensity tumor and T2-weighted image disclosed a high intensity tumor. Cystoscopy revealed a submucosal tumor on the anterior wall. Urine cytology did not suggest a malignancy. The biopsied specimens revealed only an inflammatory change in the mucosa. Partial cystectomy was carried out. He has had neither recurrence nor metastasis for 29 months. Histological diagnosis in both cases was leiomyoma of the urinary bladder.

Adult↗
PubMed1998

Extracellular glutamine level reduction enhances 5-fluorouracil cytotoxicity.

Cultured P388 (murine) and CEM (human) leukemia cells were exposed to medium including either 5-fluorouracil (5-FU) or methotorexate (MTX). The level of drug was less than the ID50 value obtained in RPMI 1640 medium (control). Enhancement of drug cytotoxicity was determined with medium in which asparagine or glutamine level had been reduced to 60% of the level of the control. Proliferation of both types of cells for 3 days showed the cytotoxicities of the drugs. Asparagine reduced medium showed no enhancement of cytotoxicity in comparison with control, while glutamine reduced medium enhanced the cytotoxicity of 5-FU, but not that of MTX. Regulation of extracellular glutamine level seemed to affect stage G1 of the cell cycle, as found in the previous result with adriamycin.

Amino Acids↗
PubMed1997

Cyclin D1 overexpression in rat two-stage bladder carcinogenesis and its relationship with oncogenes, tumor suppressor genes, and cell proliferation.

Overexpression of cyclin D1 has been implicated in the malignant transformation of a variety of human cancers, including urinary bladder carcinomas. However, few reports have addressed the significance of cyclin D1 overexpression in chemical carcinogenesis in rodents. In the present study, we evaluated the oncogenic potential of cyclin D1 in experimental rat urinary bladder carcinogenesis and its relationships to the oncogenes cyclin E, K-ras, and H-ras as well as tumor suppressor genes p53 and p21WAF1/Cip1. In addition, proliferation status of preneoplastic lesions and tumors was assessed by proliferating cell nuclear antigen immunohistochemistry. Fisher 344 rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 weeks and then administered 5% sodium L-ascorbate in diet. Animals were sacrificed at weeks 4, 8, 12, 18, and 24. Preneoplastic lesions such as papillary or nodular hyperplasia and neoplastic lesions of the urinary bladder were observed during carcinogenesis. By immunohistochemical examination, overexpression of cyclin D1 protein was observed in 17% of papillary or nodular hyperplasias, 66% of papillomas, and 69% of transitional cell carcinomas, whereas nuclear accumulation of p53 was observed in none of the preneoplastic lesions and in fewer than 2% of transitional cell carcinomas. Overexpression of cyclin D1 in preneoplastic lesions and tumors was not dependent on the size of the tumors or their proliferation status. Quantitation of mRNA in tumors by multiplex reverse transcription-PCR showed that average mRNA expression of cyclin D1 and cyclin E was increased, whereas average p21WAF1/Cip1 mRNA expression was decreased. More than 2-fold overexpression of cyclin D1 mRNA was observed in 50 and 60% of tumors at weeks 18 and 24, respectively. Localization of cyclin D1 mRNA expression was demonstrated by in situ hybridization, and the results were comparable to immunohistochemistry findings. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis harbored p53 mutations, H-ras mutations, or K-ras mutations. Thus, during the promotion phase of two-stage bladder carcinogenesis, overexpression of cyclin D1 in tumor cells may provide yet another mechanism by which tumors can gain a growth advantage. In contrast, tumors with mutated p53 may not have a growth advantage. Our results suggest that overexpression of cyclin D1 plays a critical role during urinary bladder carcinogenesis.

Animals↗