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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 397 records · Page 22Linked to original sources

Sex differences in morphology of the brain stem and cerebellum with normal ageing.

The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the cerebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women.

Adult↗

Reciprocal expression of bcl-2 and p53 oncoproteins in urothelial dysplasia and carcinoma of the urinary bladder.

In order to investigate if and when the bcl-2 oncoprotein is activated in bladder tumorigenesis and its relationship with p53 overexpression and patient survival, we studied bcl-2 and p53 expression immunohistochemically in matched normal urothelium, dysplasia and cancer specimens selected by step-sectioning from 54 radically resected bladders for non-metastatic transitional cell carcinoma (TCC). In normal urothelium and mild dysplasia, bcl-2 was restricted to the basal cell compartment, while in moderate and severe dysplasia its expression was detectable also in the upper regions. Excess bcl-2 immunoreactivity was found in 27 (50%) of carcinomas, and a larger proportion of high-grade TCCs showed bcl-2 expression compared with that of low-grade TCCs (P < 0.05). Overexpression of p53 protein showed a increasing trend toward the progression of bladder tumorigenesis (P < 0.01) and a significant reciprocal correlation was found between bcl-2 and p53 expression in either various dysplasias (P < 0.01) or carcinoma (P < 0.05). With the evolution from mild dysplasia to carcinoma in individual cases, loss of bcl-2 expression was more frequently observed in superficial (P < 0.02) or low-grade carcinoma (P < 0.05) than in muscle-invasive or high-grade carcinoma. Furthermore, patients with negative immunostaining for both bcl-2 and p53 in cancer lesions had a significantly more favorable prognosis compared with those with positive immunostaining for the oncoproteins (P < 0.05), although bcl-2 by itself did not predict patient survival. We suggest that aberrant activated bcl-2, which is seen earlier than p53, appears to facilitate bladder tumorigenesis and to enhance tumor aggression in some extent.

Aged↗

Effect of interleukin-8 on production of tumor-associated substances and autocrine growth of human liver and pancreatic cancer cells.

We have previously reported that human liver cancer cell lines produce interleukin-8 (IL-8) at high levels. Those tumor cells appeared to express two kinds of IL-8 receptor on their surface. In order to analyze the role of IL-8 on the biological characteristics of those tumor cells, we suppressed IL-8 production from human liver (HuH-7 and HuCC-T1) and pancreatic cancer cell lines (HuP-T4) by treatment with IL-8 antisense oligonucleotides. Suppression of IL-8 production resulted not only in inhibition of cell growth, but also in an increase in the concentrations of some tumor-associated substances such as carbohydrate antigen 19-9 (CA19-9) in the medium. These data indicate that IL-8 produced by human liver and pancreatic tumors may act as an autocrine growth factor and may control the production of some tumor-associated substances. Furthermore, surface expression of sialyl-Lewis(a), which is a ligand for ELAM-1 on human umbilical vein endothelial cells (HUVEC), HuCC-T1 and HuP-T4 cells was decreased and the attachment of these tumor cells to HUVEC was inhibited by treatment with IL-8 antisense oligonucleotide. Since the soluble form of CA19-9 (sialyl-Lewis(a)) was shown to inhibit the tumor cell binding to HUVEC, the decrease in release of CA19-9 into the medium and increase in the expression of sialyl-Lewis(a) on the cell surface may suggest that IL-8 production from the tumor cells enhances metastatic potential by augmenting the binding activity of the tumor cells to HUVEC. These data demonstrate that a cytokine produced by tumor cells may function as an autocrine growth factor and affect tumor cell dissemination.

Antigens, CD↗

Evaluation of ultrasound-guided fine-needle aspiration biopsy for thyroid nodules.

BACKGROUND: We retrospectively studied whether ultrasound-guided fine-needle aspiration biopsy (US-FNAB) showed improved sensitivity in patients with palpable thyroid nodules. METHODS: A total of 70 patients (72 lesions) with thyroid nodules underwent US-FNAB and 94 patients (94 lesions) underwent FNAB guided by manual palpation (standard FNAB). The diagnoses obtained by US-FNAB were compared with the surgical findings. RESULTS: The sensitivity of US-FNAB for palpable thyroid nodules was 62% the specificity was 74% the accuracy was 68% the positive predictive value was 100%, the negative predictive value was 70% and the inadequate biopsy rate was 17%. In contrast, the sensitivity of standard FNAB was 45%, the specificity was 51%, the accuracy was 48% the positive predictive value was 96, the negative predictive value was 55, and the inadequate biopsy rate was 30%. The accuracy of US-FNAB was significantly higher than that of standard FNAB. For tumors < or = 2 cm in diameter, the sensitivity and accuracy of US-FNAB were both significantly higher than those of standard FNAB. CONCLUSION: These findings suggest that US-FNAB can improve the preoperative diagnosis of thyroid cancer, especially in patients with tumors < or = 2 cm in diameter.

Adult↗

Therapeutic and diagnostic potential of a vasopressin-2 antagonist for impaired water handling in cirrhosis.

OBJECTIVE: Progressive cirrhosis is associated with increasing difficulty to handle free water. We examined the therapeutic potential of an orally active nonpeptide vasopressin-2 receptor antagonist (OPC-31260) in the management of edema and ascites in patients with cirrhosis. By means of its chemical blockade of the vasopressin-2 receptor in the kidney, we also assessed the ability of renal water handling in the early stage of cirrhosis. METHODS: A single 30 mg dose of OPC-31260 was administered orally to eight biopsy-proven patients with cirrhosis who had ascites or peripheral edema. The aquaretic responses were compared with those in six healthy subjects. RESULTS: In the patients with cirrhosis, OPC-31260 significantly (p < 0.01) increased the urinary excretion rate at 0 to 2 hours, and significantly (p < 0.01) lowered urine osmolality at 2 to 4 hours after administration. Free water clearance increased from -0.48 +/- 0.14 to +0.19 +/- 0.21 ml/min (p < 0.05) at 0 to 4 hours after administration. However, these aquaretic responses in the patients with cirrhosis were only approximately half the responses observed in the healthy subjects. A significant (p < 0.05) inverse relationship was observed between indocyanine green retention at 15 minutes after administration and the maximal free water clearance after administration to the patients with cirrhosis. Urinary sodium excretion did not change significantly in the patients, whereas it increased twofold in the healthy subjects. Urinary vasopressin excretion tended to increase in the patients, whereas it increased twofold to threefold (p < 0.01 to 0.05) from the baseline in the healthy subjects. Urinary prostaglandin E2 excretion was not increased, and serum sodium and plasma vasopressin levels were elevated only slightly in both groups. CONCLUSIONS: Even though a hyporesponsiveness was observed in the group of patients with cirrhosis compared with the healthy group, the novel vasopressin-2 antagonist induced hypotonic diuresis in patients with cirrhosis, suggesting a therapeutic potential in managing water excess. This drug response may be a new index to assess impairment of water handling in patients with cirrhosis.

Administration, Oral↗

Molecular interaction between COP1 and HY5 defines a regulatory switch for light control of Arabidopsis development.

Arabidopsis COP1 acts as a light-inactivable repressor of photomorphogenic development, but its molecular mode of action remains unclear. Here, we show that COP1 negatively regulates HY5, a bZIP protein and a positive regulator of photomorphogenic development. Both in vitro and in vivo assays indicate that COP1 interacts directly and specifically with HY5. The hyperphotomorphogenic phenotype caused by the over-expression of a mutant HY5, which lacks the COP1-interactive domain, supports the regulatory role of HY5-COP1 interaction. Further, HY5 is capable of directly interacting with the CHS1 minimal promoter and is essential for its light activation. We propose that the direct interaction with and regulation of transcription factors by COP1 may represent the molecular mechanism for its control of gene expression and photomorphogenic development.

Acyltransferases↗

Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa isolation from pharyngeal swab cultures among the Japanese elderly at admission to a geriatric hospital.

The isolation rate of Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa from pharyngeal swab cultures in the Japanese elderly was studied at admission to a geriatric hospital which had long-term care units. The subjects were 233 consecutive patients who were admitted to K Hospital in the time period April 1994 to March 1996. The isolation rate of MRSA and of Pseudomonas aeruginosa was 10.3% and 8.2% respectively. The proportions of the patients with severely to moderately limited Activities of Daily Living (ADL) (ADL score = 0-1) (P < 0.01), those with fever (P < 0.01), those with CRP positive (P = 0.04) and those with hypoalbuminemia (serum albumin < 3.5 g/dl) (P < 0.01) were higher in the MRSA positive patients than in the negative patients while the proportion of the patients with fever was higher in the Pseudomonas aeruginosa positive patients than in the negative patients (P < 0.02). In the multiple logistic regression analysis, the limitation of ADL (ADL score 0-1 vs 2-3, OR = 1.54, 95% CI = 1.02-2.33) and fever (with vs without, OR = 1.77, 95% CI = 1.18-2.66) remained as risk factors for the isolation of MRSA while only fever (with vs without, OR = 1.67, 95% CI = 1.11-2.53) remained as a risk factor for the isolation of Pseudomonas aeruginosa.

Activities of Daily Living↗

Comparison of Helicobacter pylori infection between Fukuoka, Japan and Chinju, Korea.

BACKGROUND: Helicobacter pylori is the causative agent of type B chronic gastritis, and plays a major role in the pathogenesis of gastroduodenal ulcer and gastric cancer. Because gastric cancer has been the leading cause of cancer mortality in Japan and Korea, we conducted a seroepidemiological study to estimate the prevalence of H. pylori infection in Japan and Korea in order to explain the current change in the gastric cancer incidences between two countries. MATERIALS AND METHODS: Samples used for this study included 1204 sera from Chinju, Korea and 580 sera from Fukuoka, Japan. Immunoblotting, using a sonicated crude H. pylori antigen and 1:5 dilution of serum, was performed, considering the immunoblot shows reactivity to the 120 Kd antigen of H. pylori as a specific marker of H. pylori infection. RESULTS: Seroepidemiology data from Fukuoka, Japan showed a prevalence of H. pylori infection of 20% before school age, 40% by teenage years, and over 80% beyond 20 years of age. Seroepidemiology data from Chinju, Korea, showed a 50% infection rate in preschool ages, and over 80% prevalence rate after 7 years of age. CONCLUSIONS: Lower rates of childhood H. pylori infection in Fukuoka may explain the recent decline and shift in the incidence of stomach cancer in Japan, supporting the hypothesis that H. pylori is a major determinant in the pathogenesis of stomach cancer.

Adolescent↗

Over-expression of glutathione S-transferase Yp isozyme and concomitant down-regulation of Ya isozyme in renal cell carcinoma of rats induced by ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular damage, a consequence of iron-catalysed Fenton-like reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Glutathione S-transferase (GST) is a family of enzymes that play an important role in detoxification of hydrophobic and electrophilic molecules, and has been associated with putative preneoplastic foci of rat hepatocarcinogenesis and chemotherapy-resistance of human cancers. Our previous study revealed an induction of pi-class glutathione S-transferase (Yp) mRNA in the kidney 3 h after administration of Fe-NTA. In the present study, expression of GST isozymes were further investigated in the Fe-NTA-induced RCCs of rats which are characterized by (1) high incidence of metastasis and invasion, (2) high incidence of tumour-associated mortality, and (3) possible involvement of reactive oxygen species in carcinogenesis. In the Fe-NTA-induced RCCs, the levels of alpha-class GST (Ya) mRNA and proteins were markedly decreased with no apparent change in the copy number of the gene. In contrast, GST-Yp mRNA and proteins were significantly increased in the RCCs while the total GST enzymatic activity was decreased. Immunohistochemical analysis revealed intense staining of GST-Yp not only in the primary RCCs and its metastatic sites, but also in their non-tumorous part of proximal tubules. The contrastive expression of GST isozymes in this renal carcinogenesis model suggests an alteration of its transcription mechanisms and warrants further investigation of this particular detoxifying enzyme from the viewpoint of reactive oxygen species-induced carcinogenesis.

Animals↗

cDNA cloning of canine adrenomedullin and its gene expression in the heart and blood vessels in endotoxin shock.

Adrenomedullin (AM) is a potent vasorelaxing peptide isolated from human pheochromocytoma. It is proposed that AM dilates the blood vessels by autocrine or paracrine mechanisms. Our investigation concerned whether the vasodilating function of AM accounts for the hypotension occurring in endotoxin shock. The effect of endotoxin shock on AM gene expression in the cardiovascular system was probed using a canine model. The cDNA encoding the AM precursor in dogs was isolated from cDNA libraries of the adrenal gland and was sequenced. The canine AM precursor is constituted of 188 amino acids and its AM consists of 52 amino acids, similar to human and porcine AM. The dogs were injected intravenously with 2 mg/kg of lipopolysaccharide (LPS) after being anesthetized and intubated. After 4 h, we collected whole blood, the large and small blood vessels, and the heart from our canine model of endotoxin shock, and extracted RNA from those tissues for Northern blot analysis. In the endotoxin shock model, the mRNA levels of the AM had increased in almost all of the blood vessels. These results suggest that AM may dilate the blood vessels systemically, even if AM acts as a local modulator of vascular tone. In addition, the plasma concentrations of the AM were high enough to allow for AM to act as a vasodilating hormone. Consequently, AM may be one of the factors facilitating severe hypotension complicated with endotoxin shock.

Adrenomedullin↗

Linkage mapping of the Bra, Brb and Brg genes for rat protein phosphatase 2A 55 kDa B-regulatory subunit isotypes.

We previously identified the rat Bra, Brb and Brg genes, which encode alpha, beta and gamma isotypes of the 55 kDa B-regulatory subunit of protein phosphatase 2A. Polymerase chain reaction-single strand conformation polymorphism analysis in the present study identified polymorphisms in Bra, Brb and Brg between the ACI and BUF, ZI and TM, and BN and WTC strains, respectively. Linkage analysis using mapping panels composed of F2 or back-crosses of these strains allowed Bra, Brb and Brg to be assigned to chromosomes 15, 18 and 14, respectively. Furthermore, it was revealed that Bra is located close to the Rb1 locus. Using polymorphism in Bra, loss of heterozygosity (LOH) was analyzed for rat mammary tumors induced in (SD x F344) F1 female rats by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and a typical mammary carcinogen, 7,12-dimethylbenz[a]anthracene. No LOH was detected at the Bra locus.

9,10-Dimethyl-1,2-benzanthracene↗

Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes.

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular damage that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats. The RCCs are characterized by 1) high incidence of pulmonary metastasis and peritoneal invasion, 2) high incidence of tumor-associated mortality and 3) possible involvement of reactive oxygen species in carcinogenesis. The present study investigated the possible role of Tsc2 and VHL tumor suppressor genes in this model. Thirty-four Fe-NTA-induced primary RCCs and 20 other primary or metastatic tumors of rats were searched for genetic alteration in all the coding exons of both genes by polymerase chain reaction-single-strand-conformation polymorphism analysis and sequencing in conjunction with morphological evaluation. In the Fe-NTA-induced RCCs, frequency of metastasis or invasion was proportionally associated with the nuclear grade of the tumor (grades 1-3). Only one Fe-NTA-induced RCC of grade 1 revealed missense mutations with loss of heterozygosity in exon 10 of the Tsc2 gene (codons 334, GTG (Val) to GCG (Ala), and 336, TAT (Tyr) to CAT (His). No mutation was found in the VHL gene. The results suggest that 1) high-grade RCCs can develop in the absence of mutations in the Tsc2 and VHL genes in rats, and that 2) Tsc2 gene somatic mutation can nonetheless be one of the causes of non-Eker rat RCCs.

Animals↗

Case report: intrahepatic portal-hepatic venous shunts associated with a huge pelvic leiomyoma.

We present a case of portal-systemic encephalopathy due to intrahepatic multiple portal-hepatic venous shunts. A 71-year-old woman was admitted to our hospital because of recurrent episodes of disturbed consciousness. She showed no clinical signs of portal hypertension. Liver function was normal, except for an indocyanine green retention rate of 34% at 15 min and blood ammonia level of 282 microg/dL. Portal venography revealed dilatation of the portal vein and multiple portal-hepatic venous shunts, and a liver biopsy specimen revealed almost normal liver. Further clinical examination revealed a huge pelvic tumour. At laparotomy, two dilated veins were seen to arise from the pelvic tumour with blood flow into the mesentery. The tumour was resected successfully and a histological diagnosis of leiomyoma was made. The blood ammonia concentration decreased to the normal range postoperatively. A follow-up portal venogram demonstrated decreased portal vein dilatation and minor portal-hepatic venous shunts, considered to be congenital in origin. It is concluded that hepatic encephalopathy was produced in this patient due to an excess portal blood flow from the huge pelvic leiomyoma via the mesentery, with portosystemic shunting through pre-existent (probably congenital) intrahepatic anastomoses.

Aged↗

Cartilaginous membranocystic lesions mimicking membranous lipodystrophy of bone.

Two cases are presented in which membranocystic lesions were observed in the cartilaginous tissue of surgical specimens. In both cases, the histological and ultrastructural features were reviewed, and S-100 protein distribution was examined immunohistochemically in one case. In both cases, the membranocystic lesions were observed to be adjacent to ballooned chondrocytes. In one case, several chondrocytes showed partially membranocystic lesions in their cytoplasm. The chondrocytes and nuclei in membranocystic lesions were stained positively for S-100 protein. It is suggested that the membranocystic lesions in the cartilaginous tissue were associated with the degeneration of the chondrocytes.

Adolescent↗

Pseudosarcomatous myofibroblastic tumor of the urinary bladder with massive intraperitoneal hemorrhage in a child.

A 3-year-old boy presented with persistent abdominal pain, hematuria and facial pallor with progressive anemia. A computed tomography scan showed a massive intraperitoneal hemorrhage and tumor mass in the bladder. Histological examinations of the resected tumor revealed findings of pseudosarcomatous myofibroblastic tumor (PMT). The clinico-pathological features of this case warn us that PMT can cause acute abdomen syndrome with massive intraperitoneal hemorrhage.

Abdomen, Acute↗

Evaluation of the prognostic significance of microvessel count and tumor size in renal cell carcinoma.

BACKGROUND: We analyzed the significance of tumor microvessel count and tumor size as prognostic factors for renal cell carcinoma (RCC). METHODS: T criteria (local invasion), M criteria (distant metastasis), macrovenous invasion, histological grade, cell type, tumor size, and tumor microvessel count were investigated as prognostic factors in 62 patients with RCC. Microvessel density was evaluated by immunohistochemical staining of the endothelial cells. RESULTS: No significant correlation was found between tumor size and the other prognostic factors. Analysis of the survival rate based on tumor size revealed that patients with a small tumor tended to show a good prognosis, but no significant difference was found in the prognosis between medium-sized and large-sized tumor groups. Analysis of all patients revealed that M criteria, macrovenous invasion, cell type and microvessel count were significant factors and that in 37 patients with low-stage tumors, the only significant prognostic factor was microvessel count (P=0.003). CONCLUSION: Tumor size cannot be readily justified as a determinant of prognosis in patients with medium- or large-sized tumors. In patients with low-stage tumors, microvessel count served as the only significant determinant for prognosis. When the patients were considered as a whole, microvessel count, M criteria, macrovenous invasion and histological grade were significant prognostic factors.

Adult↗