Biomedical subjects

F Ito

Publications and source records attributed to F Ito.

At least 73 records · Page 4Linked to original sources

PubMed1998

Aberrant expression and phosphorylation of beta-catenin in human colorectal cancer.

The cytoplasmic domain of cadherins is known to associate with the intracellular proteins, catenins, which link cadherins to the actin-based cytoskeleton. In this study, we immunohistochemically investigated the expression of beta-catenin as well as E-cadherin and alpha-catenin in 86 human colorectal cancers, and we analysed their coexpression pattern and relationship to clinicopathological factors. In cancerous tissues, the frequency of reduced expression of beta-catenin (28 of 86, 33%) was similar to that of E-cadherin (19 of 86, 22%), but less than that of alpha-catenin (47 of 86, 55%). All three molecules were expressed strongly, as was the normal epithelium, in 36 cases (42%), whereas the rest (50 cases, 58%) showed reduction in one of the molecules. The reduction of beta-catenin expression was significantly correlated with dedifferentiation, Duke's stage, lymph node metastasis and liver metastasis. Next, we examined tyrosine phosphorylation in the protein complex immunoprecipitated with E-cadherin, as E-cadherin function is down-regulated by receptor-type tyrosine kinase in vitro. It was of interest that up-regulation of tyrosine phosphorylation of beta-catenin was more frequently observed in cancerous tissues than in the matching normal mucosa. These results suggest that beta-catenin may have important regulatory roles within an E-cadherin-mediated adhesion system in human colorectal cancers.

Cadherins↗

PubMed1998

Cytoskeletal reorganization by soluble Wnt-3a protein signalling.

BACKGROUND: Wnt-3a is an intercellular signalling molecule that is involved in a variety of morphogenetic events. However, the molecular mechanisms underlying Wnt-3a signalling are poorly understood. We have sought to establish in vitro systems to assay the activity of this protein and investigate its biological roles. RESULTS: We prepared mouse L cells transfected with Wnt-3a cDNA, and found that their beta-catenin protein level was up-regulated. When conditioned medium (CM) was collected from cultures of the transfectants and added to nontransfected L cells, the beta-catenin level of the latter was also increased. Approximately 50% of the Wnt-3a proteins synthesized by the transfectants were secreted into the CM in a soluble form. These secreted Wnt-3a proteins formed an activity gradient in the environment surrounding the transfectants. Then, we studied whether Wnt-3a had any effect on cellular behaviour in vitro. When the CM containing Wnt-3a (W3a-CM) was added to cultures of C57MG mammary epithelial cells, their morphology was altered to exhibit closer intercellular contacts. Immunostaining for various adhesion and cytoskeletal proteins showed that the actin-microfilamental system was re-organized by the W3a-CM treatment. It induced a directional alignment of actin stress fibres and other actin-associated proteins. Moreover, villin, localized only at the perinuclear regions in untreated C57MG cells, was re-distributed to the leading edges of the cells, co-localizing with F-actin, in the presence of Wnt-3a. CONCLUSION: Our findings suggest that Wnt-3a protein, in the soluble form, can act to re-organize cytoskeletal structures.

Actins↗

PubMed1998

A rat model of chemical-induced polycystic kidney disease with multistage tumors.

Diphenylthiazole (DPT) induces polycystic kidney disease in the rat which serves as a model of human acquired cystic disease of the kidney. However, DPT administration alone does not produce neoplastic changes in renal cysts. We examined the effect of N-nitrosomorpholine (NNM), a carcinogen, in rats bearing DPT-induced renal cysts. Forty Sprague-Dawley rats were divided into four groups: DPT/NNM, DPT, NNM, and nontreated groups. DPT was administered throughout the experimental period, and NNM was given from weeks 4 to 7 after the start of the experiment. The rats were sampled from weeks 39 to 48, and histopathological examinations of the excised kidneys were performed. Multiple cystic changes were observed in all the DPT-treated rats in both DPT and DPT/NNM groups which were absent in almost all other rats. Solid adenomatous lesions were observed in the NNM-treated rats: in 7 of 9 and in 3 of 10 rats in the DPT/NNM and NNM groups, respectively. Cystic adenomatous lesions were found in 4 of 9 rats in the DPT/NNM group exclusively and not in the other groups. Combined DPT and NNM administration to rats produced an animal model showing neoplastic changes in renal cysts resembling microscopically renal cancer lesions in human acquired cystic disease of the kidney (on hematoxylin and eosin staining).

Animals↗

PubMed1998

[A juxtaglomerular cell tumor. Analysis of immunohistochemistry, electron microscopy and in situ hybridization].

We present a case of juxtaglomerular cell tumor measuring 8 mm in diameter in the right kidney. The hypertension was cured and plasma renin activity returned to normal level following tumor resection with partial nephrectomy. We studied histopathologic, electron microscopic, and immunohistochemical findings of the tumor. The majority of tumor cells stores renin granules in cytoplasm. In situ hybridization confirmed us that the most tumor cells produce renin. We use the digoxigenin labeled 0.6-kb length RNA probe of human renal renin, the specificity was analyzed by competition assay (1:50).

Adenocarcinoma↗

PubMed1998

Treatment of hepatoblastoma: less extensive hepatectomy after effective preoperative chemotherapy with cisplatin and adriamycin.

BACKGROUND: Although the prognosis of hepatoblastoma was improved by the introduction of cisplatin and doxorubicin (Adriamycin) for adjuvant chemotherapy, extensive hepatectomy continues to be the usual practice. We retrospectively reviewed our recent experience with hepatoblastoma to determine whether the new modality of intensive chemotherapy could change the resectability, extent of hepatectomy, operative complications, and prognosis. METHODS: The clinical features of 15 children with hepatoblastoma treated between 1985 and 1995 were reviewed. Intensive chemotherapy was added before surgical resection not only when a tumor was unresectable but also when it was large enough to increase the risk of operative morbidity. RESULTS: There was 100% resectability, and the overall mortality rate was only 6.7%. Fourteen patients have been free of disease for 2 to 12 years. Preoperative chemotherapy enabled resection of six previously unresectable hepatoblastomas. Moreover, hepatic resection tended to be less invasive in several patients whose tumors had been much reduced after preoperative chemotherapy. Intraoperative and postoperative complications were minimal, with a short operative time and small amount of blood loss, especially in the group with delayed primary operation. CONCLUSIONS: The preoperative administration of cisplatin and Adriamycin reduced the tumor size so that a safe hepatectomy could be performed with less blood loss and minimal technical complications. Unnecessary sacrifice of the normal hepatic tissue was avoided by performing the less extensive hepatectomy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

[Study on urinary levels of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in patients with renal cell carcinoma].

We examined the preoperative and postoperative, urinary levels of the cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in 14 patients with renal cell carcinoma (RCC), and 9 patients who underwent nephrectomy as donors (controls). Although urinary IL-1 beta was measurable in every subject, both IL-6 and TNF-alpha were undetectable in 12 of the 14 patients. None of the urinary cytokines showed levels significantly different from the controls preoperatively. Urinary levels of IL-1 beta showed no correlation with clinical stage or histological grade. Only urinary IL-1 beta was significantly elevated after nephrectomy, when compared with the controls (P < 0.05). However, urinary IL-1 beta showed no correlation with operative blood loss or postoperative infection. These findings suggest that measurement of urinary cytokines is not useful for diagnosis or monitoring of therapy in RCC patients.

Adult↗

PubMed1998

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

PubMed1997

Phospholipase A2 is necessary for tumor necrosis factor alpha-induced ceramide generation in L929 cells.

The role of cytosolic phospholipase A2 (cPLA2) in the regulation of ceramide formation was examined in a cell line (L929) responsive to the cytotoxic action of tumor necrosis factor alpha (TNFalpha). In L929 cells, the addition of TNFalpha resulted in the release of arachidonate, which was followed by a prolonged accumulation of ceramide occurring over 5-12 h and reaching 250% over base line. The formation of ceramide was accompanied by the hydrolysis of sphingomyelin and the activation of three distinct sphingomyelinases (neutral Mg2+-dependent, neutral Mg2+-independent, and acidic enzymes). The variant cell line C12, which lacks cPLA2, is resistant to the cytotoxic action of TNFalpha. TNFalpha was able to activate nuclear factor kappaB in both the wild-type L929 cells and the C12 cells. However, TNFalpha was unable to cause the release of arachidonate or the accumulation of ceramide in C12 cells. C6-ceramide overcame the resistance to TNFalpha and caused cell death in C12 cells to a level similar to that in L929 cells. The introduction of the cPLA2 gene into C12 cells resulted in partial restoration of TNFalpha-induced arachidonate release, ceramide accumulation, and cytotoxicity. This study suggests that cPLA2 is a necessary component in the pathways leading to ceramide accumulation and cell death.

Animals↗

PubMed1997

Genomic organization and complete nucleotide sequence of the human PWP2 gene on chromosome 21.

The human PWP2 gene is the human homologue of the yeast periodic tryptophan protein 2 (PWP2) gene and is a member of the gene family that contains tryptophan-aspartate (WD) repeats. Genomic sequencing revealed that the human PWP2 gene consists of 21 exons spanning approximately 24 kb and locates just between the two genes EHOC-1 and KNP-I and distal to a NotI site of LJ104 (D21S1460) on chromosome 21q22.3. Analysis of the 5'-flanking DNA sequence revealed that the upstream region of the PWP2 gene is associated with a CpG island containing the NotI site of LJ104. Since PWP2 is considered to be a candidate for genetic disorders mapped in the 21q22.3 region, the information including nucleotide sequence and genomic organization of the PWP2 gene should be invaluable for the mutation analysis of the corresponding genetic disorders.

Base Sequence↗

PubMed1997

Genomic organization and complete nucleotide sequence of the TMEM1 gene on human chromosome 21q22.3.

TMEM1 (EHOC-1) gene encodes a putative transmembrane protein and is located on human chromosome band 21q22.3. Analysis of a 122,638-bp genomic sequence revealed that TMEM1 gene consists of 23 exons spanning approximately 94 kb and is transcribed in the direction of centromere to telomere. The 5' region of the TMEM1 gene was associated with a CpG island and the 3' end of the TMEM1 gene was mapped just proximal to the 5' end of the neighboring gene PWP2. We determined that the TMEM1 gene encodes a protein of 1,259 amino acids, which is 69-amino acids longer than the previously reported sequence. Since TMEM1 gene is considered to be a candidate for genetic disorders mapped in the 21q22.3 region, the information including complete nucleotide sequence and genomic organization of the TMEM1 gene should be invaluable for the mutation analysis of the corresponding genetic disorders.

Amino Acid Sequence↗

PubMed1997

Localization of 16 exons to a 450-kb region involved in the autoimmune polyglandular disease type I (APECED) on human chromosome 21q22.3.

As a step toward identifying the pathogenic genes for autoimmune polyglandular disease type I (APECED) and other disorders mapped to the PFKL locus on chromosome 21q22.3, we have constructed a cosmid/BAC (bacterial artificial chromosome) contig of 450 kb covering markers D21S1460-D21S25-PFKL-D21S154 and performed exon trapping. We isolated 22 distinct exons including 6 exons derived from two known genes (PFKL and EHOC-1). Among 16 novel exons, 2 exons matched with human expressed sequence tags (EST) and 7 exons showed homology at predicted amino acid sequence level with proteins from other species. These 16 exons were mapped back to the cosmid contigs, 12 of which were confirmed for their expression by polymerase chain reaction (PCR) screening of human cDNA libraries of various tissues. These exon sequences and a transcript map will aid for isolation of corresponding genes which will be identified as candidate genes involved in the pathogenesis of disorders mapped to the 21q22.3 region.

Amino Acid Sequence↗

PubMed1997

Cystic coccygeal medullary vestige presenting as a sacrococcygeal mass: a case report and MRI findings.

The case of a 10-month-old boy with a cystic coccygeal medullary vestige is presented. Although the MRI findings of this lesion resemble those of sacrococcygeal teratomas, the presence of a cystic component located at the tip of the coccyx and associated sinus formation may help in diagnosing it. Cystic coccygeal medullary vestige should be entertained in the differential diagnosis of coccygeal cystic lesions.

Cysts↗

PubMed1997

Operative treatment of congenital stenoses of the intrahepatic bile ducts in patients with choledochal cysts.

BACKGROUND: Postoperative complications including intrahepatic calculi may develop after the complete excision of a choledochal cyst. Since congenital stenoses of the intrahepatic bile ducts are more likely the cause of intrahepatic calculi, operative procedures for intrahepatic stenoses are reported. METHODS: There were 16 patients with choledochal cysts who underwent surgery for stenoses of intrahepatic bile ducts. The stenoses were excised at the opening of the common hepatic duct. RESULTS: In the 16 patients, 25 of the 26 stenoses that involved an intraluminal membrane or septum could be excised from the divided end of the common hepatic duct at the hepatic hilum. In 1 patient, the stenosis could not be accessed from the hepatic hilum, and a left hepatic lobectomy was required. In postoperative follow-up, all 16 patients were in good health. CONCLUSIONS: Stenoses of the intrahepatic bile ducts should be treated from the divided end of the common hepatic duct at the initial operation for choledochal cysts. The need for a second operation or hepatic lobectomy may thus be avoided.

Adolescent↗

PubMed1997

Correlation between shrinkage of uterine leiomyoma treated with buserelin acetate and histopathologic findings of biopsy specimen before treatment.

OBJECTIVE: To analyze histopathologic features related to myoma volume reduction after treatment with a GnRH agonist, buserelin acetate, in needle biopsy specimens obtained before treatment. DESIGN: Prospective clinical study. SETTING: University teaching hospital. PATIENT(S): Twenty women with normal menstrual cycles and symptomatic uterine myomas. INTERVENTION(S): Buserelin acetate was administered intranasally (900 micrograms/d) for at least 16 weeks; transcervical needle biopsy of the uterine myoma was done before this treatment. MAIN OUTCOME MEASURE(S): The relation between histopathologic features (degree of cellularity, hyaline change, and collagen content) and the percent decrease in the volume of the largest myoma at 16 weeks measured by magnetic resonance imaging. RESULT(S): The correlation between the degree of hyaline change and the percent decrease in the myoma volume was significant, as was that with the proportion of collagenous tissue in the specimens. CONCLUSION(S): We predicted myoma volume reduction after treatment with a GnRH agonist by histologic analysis of the uterine leiomyoma before treatment.

Administration, Intranasal↗

PubMed1997

Biochemical and morphological changes in the liver during isolated liver perfusion with double bypass using automatic blood pumps.

Isolated organ perfusion is used in clinical practice for chemotherapy in adults with malignant tumors. However, it has not been performed in children because of the size mismatch with the adult circuits. The authors have previously studied isolated liver perfusion in small animals using the self-regulating extracorporeal membrane oxygenation circuit. The present study was designed to investigate the biochemical and morphological changes in the liver during isolated liver perfusion with double bypass using automatic blood pumps. Isolated liver perfusion was performed with bypass between the hepatic and portal veins in seven weanling Yorkshire swine weighing 8.2 to 12.2 kg, at a flow rate of 20 mL/min/kg for up to 4 hours. Venous blood from the intestine and lower body was bypassed to the superior vena cava. As a result, perfusate glutamic pyruvic transaminase and lactate concentrations did not change during liver perfusion. On gross inspection, the surface of the liver was mottled. Microscopically, normal histology of the hepatic parenchyma and portal tract structures was preserved. Transmission electron microscopy showed no gross structural abnormalities in most of the hepatocytes for up to 4 hours. However, swelling of the mitochondria and smooth endoplasmic reticulum was seen occasionally in a very small number of the hepatocytes after more than 3 hours of perfusion. Glycogen granules decreased with time in some animals. Isolated liver perfusion at 20 mL/min/kg of perfusion flow can be performed safely for up to 4 hours with nearly intact hepatocellular function and morphology.

Alanine Transaminase↗

PubMed1997

A new hepatic portoenterostomy with division of the ligamentum venosum for treatment of biliary atresia: a preliminary report.

BACKGROUND/PURPOSE: Kasai's operation consists of transection of the fibrous portal cord including the bile duct remnant. However, it is difficult to transect the fibrous cord at the level of the posterior surface of the portal vein, because the portal vein is fixed at the porta hepatis. METHODS: The authors described a new hepatic portoenterostomy to transect the fibrous cord under an appropriate visual field by division of the ligamentum venosum (Arantius' canal). Between February and December 1996, six patients who had biliary atresia underwent this procedure. RESULTS: Jaundice resolved completely (TB < or = 1.0 mg/dL) in all six patients within 40 days. Postoperative cholangitis did not occur and good bile drainage was obtained. CONCLUSIONS: Using this procedure, the portal vein becomes fully mobile after dividing the ligamentum venosum, and the porta hepatis can be widely exposed. The fibrous cord of the porta hepatis can be easily dissected off posteriorly and laterally.

Biliary Atresia↗

PubMed1997

Obstructive jaundice, an unusual initial manifestation of intraabdominal non-Hodgkin's lymphoma in children: complications of percutaneous transhepatic cholangial drainage.

Obstructive jaundice is an unusual initial manifestation of non-Hodgkin's lymphoma in children. Two pediatric patients with primary intraabdominal non-Hodgkin's lymphoma causing obstructive jaundice are presented. Although percutaneous transhepatic cholangial drainage (PTCD) is frequently used to treat obstructive jaundice, there was no definite rule for management of PTCD during chemotherapy, which may rapidly resolve the obstruction. Biliary peritonitis occurred in both patients soon after removal of the PTCD tube after chemotherapy. It was speculated that secure formation of the fistula for PTCD was impaired because of chemotherapy for a considerably long period. The PTCD tube that was already placed for obstructive jaundice in a non-Hodgkin's lymphoma patient should be maintained during chemotherapy with great care for displacement of the tube. PTCD can result in complications, and is probably unnecessary when lymphoma has been diagnosed before PTCD.

Abdominal Neoplasms↗

PubMed1997

Positional cloning of the APECED gene.

Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C-->T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A-->G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.

Amino Acid Sequence↗