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Biomedical subjects

K Furuta

Publications and source records attributed to K Furuta.

At least 73 records · Page 4Linked to original sources

Hypoglycemic effect of the rhizomes of Smilax glabra in normal and diabetic mice.

The hypoglycemic effect of the rhizomes of Smilax glabra ROXBURGH (Liliaceae) was investigated in normal and KK-Ay mice, one of the animal models of non-insulin dependent diabetes mellitus (NIDDM) with hyperinsulinemia. The methanol extract of rhizomes of Smilax glabra ROXBURGH (SM, 100 mg/kg body weight) reduced the blood glucose of normal mice 4 h after intraperitoneal administration (p<0.05), and also significantly lowered the blood glucose of KK-Ay mice under similar conditions (p<0.001). However, SM did not affect the blood glucose in streptozotocin-induced diabetic mice, one of the animal models of insulin-dependent diabetes mellitus (IDDM) with hypoinsulinemia. SM also suppressed epinephrine-induced hyperglycemia in mice. SM-treated KK-Ay mice significantly decreased the blood glucose in an insulin tolerance test. We concluded that the hypoglycemic effect of SM raised insulin sensitivity.

Animals↗

Hypoglycemic activity of to-kai-san (Chinese medicines) in normal and KK-Ay mice.

The hypoglycemic effect of To-Kai-San (TS) was studied in normal mice, streptozotocin-induced diabetic mice, one of the animal models of insulin-dependent diabetes mellitus (IDDM) with hypoinsulinemia, and KK-Ay mice, one of the animal models of non-insulin-dependent diabetes mellitus (NIDDM) with hyperinsulinemia. TS (1,500 mg/kg) reduced the blood glucose of the KK-Ay mice from 441 +/- 36 to 285 +/- 52 mg/100 ml 7 h after a single oral administration (p < 0.001). However, no changes in blood glucose were observed in the normal and STZ-induced diabetic mice. TS also decreased the blood glucose 20 days after repeated administration to normal and KK-Ay mice. In addition, TS-treated KK-Ay mice showed decreased plasma insulin levels after both single and repeated administration. From these findings, it is believed that TS may require the presence of insulin to display its activity.

Administration, Oral↗

A simpler and more reliable technique of pancreatojejunal anastomosis.

We herein describe the technical aspects of our method for end-to-side style pancreatojejunal anastomosis which we have been using when performing the Whipple procedure without any anastomotic complications. The method is simple and can be applied wherever an end-to-side pancreatojejunal anastomosis is required. It consists of three steps: First, a drainage tube is inserted into the pancreatic duct. Second, a direct anastomosis between the pancreatic duct and the mucosal layer of the jejunal loop is performed. The third step, which is the unique aspect of our method, is an approximation of the jejunal wall and the pancreatic stump by a one-layer suture technique that allows us not only to reduce the number of sutures but also to eliminate some of the sophisticated manipulations required by other methods. The results of our clinical experience have indicated that the present method may be comparable in terms of technical reliability to other existing methods.

Anastomosis, Surgical↗

Induction of MRP/GS-X pump and cellular resistance to anticancer prostaglandins.

We provide evidence that the expression of the human MRP/GS-X pump encoded by the MRP (multidrug resistance associated protein) gene is induced by cisplatin in human leukemia HL-60/R-CP (cisplatin-resistant) cells and modulates cell growth inhibition by delta(7)-prostaglandin A1 (PGA1) methyl ester. The MRP mRNA level in HL-60/R-CP cells increased remarkably after a 24-h incubation with 20 microM cisplatin; interestingly, however, no amplification of the MRP gene was detected. In cisplatin-sensitive HL-60 cells, which express the MRP/GS-X pump at low levels, c-myc expression was substantially suppressed by delta(7)-PGA1 methyl ester and the cell cycle was arrested in G1 phase. By contrast, in HL-60/R-CP cells overexpressing the MRP/GS-X pump, c-myc expression and cell proliferation were much less affected by delta(7)-PGA1 methyl ester. This suggests that induction of the MRP/GS-X pump may confer on cancer cells resistance to anticancer prostaglandins and that the resistance mechanism may involve the increased efflux of PG-glutathione conjugates, as active intermediates, from the cells via the MRP/GS-X pump.

ATP-Binding Cassette Transporters↗

Thoracoscopic splanchnicectomy for the relief of intractable abdominal pain.

Video-thoracoscopic transthoracic splanchnicectomy has been applied to patients in the end stage of pancreas cancer who had intractable pain mediated through the splanchnic nerve in the left upper quadrant. The procedure is performed under general anesthesia in a right hemilateral position. Following the establishment of access to the thoracic cavity, the left splanchnic nerve is cut off at the level immediately above the aortic hiatus, through a small opening made in the pleura between the descending aorta and the vertebrae. All patients had immediate and complete relief of pain postoperatively. Only a transient drop in the mean arterial pressure was observed immediately after cutting off the nerve. No other detrimental effect of the procedure on the general condition was observed. No patients developed postoperative complications. The present method may, thus, be a treatment of choice directed toward the relief of intractable abdominal pain in selected patients with pancreatic cancer.

Abdominal Pain↗

Replication protein-A mediates the association of calf thymus DNA polymerase alpha-DNA primase complex with guanine-rich DNA sequence.

We have shown that calf thymus DNA polymerase alpha-DNA primase complex (pol alpha-primase) preferentially binds to pyrimidine-rich sequences and initiates RNA primer synthesis [Suzuki, M. et al. (1993) Biochemistry 32, 12782-12792]. Here we tested the association of pol alpha-primase with a guanine-rich DNA fragment (SVG, 30-mer) containing in vivo initiation sites of simian virus 40 DNA replication. While pyrimidine-rich fragment (CTPPS 1, 30-mer), that is a preferred sequence for calf thymus DNA primase, was well co-precipitated with pol alpha-primase using anti-pol alpha antibody, SVG was hardly precipitated under the same conditions. Competition studies in either gel-retardation assay or during de novo DNA synthesis by pol alpha-primase demonstrated that the interaction of pol alpha-primase with SVG was much weaker than that with CTPPS-1. On the other hand, replication protein-A (RP-A) could bind SVG, although less efficiently than CTPPS 1. After preincubation with RP-A, SVG could bind pol alpha-primase that was immobilized on Sepharose beads. The simian virus 40 large T antigen also enhanced association of SVG to pol alpha-primase, while Escherichia coli single-stranded DNA-binding protein did not. However, pol alpha-primase, bound to SVG in the presence of RP-A, failed to synthesize RNA primers. When SVG was extended 10 nucleotides at its 5'-end, pol alpha-primase synthesized trace amounts of RNA primers, and this activity was stimulated more than 10-fold by adding RP-A. These results suggest a new role for RP-A, i.e., as a molecular tether that allows pol alpha-primase to bind guanine-rich regions of DNA in order to initiate RNA primer synthesis.

Animals↗

[Evaluation of differential media in Helicobacter pylori culture].

Culture is one of the important methods for detecting Helicobacter pylori(Hp). Culture method is generally lower sensitive in comparison with other Hp detection methods. However, culture is necessary for determination of MIC and analysis of bacteriological characteristics. Several culture media are now commercially available for Hp. In this study, we compared commercial media with our original medium. Original medium for Hp culture was most sensitive and showed no false-positive results compared with other commercial media.

Culture Media↗

Relationship between CD44 expression and cell proliferation in epithelium and stroma of colorectal neoplasms.

The cell surface glycoprotein CD44 is expressed primarily in the region of cell replication in the lower crypt epithelium of colorectal mucosa, and its expression is markedly increased in colorectal neoplasms, suggesting that expression is linked to proliferation. The association between CD44 expression and replication in individual cells was therefore analyzed by double-label immunohistochemistry for CD44 and the cell-cycle-dependent protein proliferating cell nuclear antigen (PCNA). Enhanced expression of CD44 in colorectal neoplasms occurred not only in epithelial cells but also in stromal cells, including lymphocytes and macrophages. On a topographical basis, the cellular localization of CD44 and PCNA were commonly different. Quantitatively, in all cell types studied (epithelial cells and stroma of colorectal mucosa, adenomas, and carcinomas) PCNA was present most frequently in cells lacking CD44. Statistical analysis by logistic regression models indicated that cells negative for CD44 had a higher probability of being positive for PCNA than did cells positive for CD44 (P < 0.001). These data suggest that the enhanced level of CD44 in colorectal neoplasms is asynchronous with cell replication and reflects mechanisms that act on nonproliferative stromal lymphocytes and other mononuclear cells as well as the epithelial cells.

Adult↗

Pharmacological properties of KT3-671, a novel nonpeptide angiotensin II receptor antagonist.

We examined pharmacological profiles of KT3-671, 2-propyl-8-oxo-1-[(2'-(1H-tetrazole-5-yl) biphenyl-4-yl)methyl]- 4,5,6,7-tetrahydro-cycloheptimidazole, a newly synthesized nonpeptide angiotensin II (AII) receptor antagonist in various in vitro and in vivo studies. KT3-671 displaced specific binding of [125I]Sar1 Ile8-AII to AT1 receptor with a Ki value of 0.71 +/- 0.14 x 10(-9) M in rat liver membranes, but had no affinity for AT2 receptor in bovine cerebellar membranes (Ki > 10(-5) M). In isolated rabbit aorta, KT3-671 produced a parallel rightward shift in the concentration-response curve for AII with a pA2 value of 10.04 +/- 0.12, but had no effect on KCl-, norepinephrine (NE)-, and serotonin (5-HT)-induced contractions. In conscious normotensive rats, KT3-671 (0.3-10 mg/kg, p.o.) inhibited the AII-induced pressor response dose dependently. In renal artery-ligated hypertensive rats, KT3-671 (0.1-3 mg/kg, p.o.) decreased arterial blood pressure (BP) dose dependently. The hypotensive action of 3 mg/kg KT3-671 was maintained for at least 24 h. These results suggest that KT3-671 is a potent AT1 subtype-selective and competitive nonpeptide AII receptor antagonist and has an orally active antihypertensive effect without agonistic activity.

Angiotensin II↗

Autoantibody to DNA topoisomerase II in primary liver cancer

A patient with chronic hepatitis associated with hepatitis C virus infection was observed to convert from antinuclear antibody-negative to antinuclear antibody-positive status at the time when liver cancer was detected. The newly recognized antibodies reacted with a nuclear protein doublet of 170 and 180 kDa in immunoblotting, and in fluorescence-activated flow cytometry the antigens were shown to vary in expression level in a cell cycle-related manner: minimum in G1, increasing in S, and maximum in G2 and M. In synchronized HeLa and HEp-2 cells, immunofluorescence microscopy showed uniformly distributed staining of the nucleoplasm in S-phase, with increased intensity of nucleoplasmic staining in G2, at which time nucleolar staining was also present. In M, condensed chromosomes were uniformly stained. Using previously characterized polyclonal antibodies to DNA topoisomerase II (topo II) as reference markers, the antigens recognized by the patient's serum were shown in Western blotting to have the same mobilities as DNA topo IIalpha (170 kDa) and beta (180 kDa) isoforms. The patient's serum was also highly efficient in inhibiting DNA topo II in an in vitro functional assay. Antibody to DNA topo II appeared de novo in close association with transformation to cancer, and since dysregulation of DNA topo II is considered to be involved in some forms of tumorigenesis, the observed antibody response in this patient could conceivably be an immune reaction to the abnormally regulated protein.

Journal Article↗

Cavernous transformation of the portal vein coinciding with early gastric cancer and cholelithiasis.

A 71-year-old man who developed jaundice with a high-grade fever was admitted to our hospital. The episode was ascribed to cholecysto-choledocholithiasis. In the preoperative evaluation, a cavernous transformation of the portal vein and an early gastric cancer were found. The patient thereafter underwent an operation for those pathologies after the endoscopic removal of a choledochal stone; cholecystectomy, and a distal gastrectomy with regional lymph node dissection for gastric cancer. The proposed procedures of gastrectomy and cholecystectomy were completed without any major difficulty because no markedly enlarged collateral veins were found in the area where the regional lymph node dissection was carried out. Thanks to advances in imaging modalities, an asymptomatic cavernous transformation of the portal vein coinciding with gastric cancer such as that seen in the present case may be increasingly encountered in the future. The greatest caution, however, needs to be exerted at operation to minimize any unexpected bleeding and to avoid any interruption of the porto-portal shunts in such cases. Further, the reestablishment of the portal blood supply to the liver might be required in advanced cases of gastric cancer, where regional lymph node dissection may necessitate skeletonization of the hepatoduodenal ligament for curative purposes.

Adenocarcinoma↗

Transmission of hepatitis C in an isolated area in Japan: community-acquired infection. The South Kiso Hepatitis Study Group.

BACKGROUND/AIMS: The spread of hepatitis C virus (HCV) infection not due to drug needle sharing or transfusion is largely unknown in communities. A search for risk factors for HCV infection in an endemic area might elucidate inapparent modes of transmission. METHODS: We conducted screening for hepatitis virus markers and parenteral exposures to blood among 435 inhabitants in an isolated area known for its endemicity for non-A, non-B hepatitis and in a nonendemic area with 1542 inhabitants. RESULTS: The prevalence of hepatitis B surface antigen was the same in both areas. The prevalence of antibody to HCV verified by the recombinant immunoblot assay was 32.4% in the highly endemic area and 2.3% in the nonendemic area (P < 0.001). Risk factors for HCV infection in the highly endemic area were complex but included folk remedies such as acupuncture and "vacuuming" for congested blood in muscle by the use of a warm glass bottle. CONCLUSIONS: Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives should be considered as possible routes of HCV transmission not associated with blood transfusion or sharing of drug paraphernalia.

Adolescent↗

Reduction of aluminium concentration in albumin products.

The aluminium concentration in albumin products has been reduced to < or = 100 ppb by an anion exchanger treatment. Furthermore, we have found that this low aluminium concentration in a albumin products has been maintained for extensive periods of time, when they are stored in de-alkalized soft glass containers.

Aluminum↗

[Tissue blood flow of the sigmoid colon for safe anastomosis following ligation of the inferior mesenteric artery].

We examined the tissue blood flow (TBF) of the sigmoid colon to determine which level of inferior mesenteric artery. In 13 patients, TBF of the sigmoid colon was measured in the control state and the clamped state, in which the inferior mesenteric artery (IMA), left colic artery and the rectal were wall clamped. In the clamped state, means of TBF at 10 cm and 15 cm distal to the descend-sigmoid junction were 1.87 +/- 0.77 and 1.10 +/- 0.40, respectively. Mean of TBF at 15 cm was significantly lower than that at 10 cm. In conclusion, TBF which is enough for safe anastomosis reaches as far as 10 cm distal from the descend-sigmoid junction after ligation of IMA. Anastomosis at this level in anterior resection of the rectum is safe in concerning with TBF.

Adult↗

[A clinical study of the changes of bone lesions after parathyroidectomy in patients with secondary hyperparathyroidism].

We evaluated the changes of the bone lesions and their relative bone findings before and after parathyroidectomy in 23 patients with secondary hyperparathyroidism. Before the operation, all patients had bone and/or joint pain. In radiographic findings, subperiosteal bone resorption of the hand and a salt and pepper coloration of the skull were observed in all patients. Rugger jersey spine and the disappearance of the lamina dura were observed in about 90% of the patients. The bone mineral contents measured by single photon absorptiometry and digital image processing method had decreased in all of the patients compared with the mean values in sex- and age-matched controls. After the operation, the bone and/or joint pain had disappeared excluding three patients with recurrent hyperparathyroidism. The bone changes of the hand and the skull had improved in about 90% of the patients. However, the improvement rate was low in the vertebral and dental bone changes. The bone mineral contents increased significantly compared with the preoperative values. In recurrent cases, transient increase of the bone mineral contents was observed postoperatively. However, their values, were decreased gradually with the elevation of parathyroid hormone level. The evaluation of the bone lesions before and after parathyroidectomy not only indicates the effectiveness of the operation but also illustrates the function of the autotransplanted parathyroid tissues. We conclude that regular examination of the bone lesions after parathyroidectomy, paying attention to recurrent hyperparathyroidism and/or graft function, is mandatory.

Adult↗

Comparison of the clinical and immunogenetic features between patients with autoimmune hepatitis and patients with type C chronic active hepatitis.

We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis (C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH. The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH predominantly. Ongoing or past infection of HCV was seen in only 14% of patients with AI-CAH. HLA-DR4 was the most frequently associated with AI-CAH (89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg on DR2 and His on DR4), may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted, disease, and different from C-CAH which is a viral infectious disease.

Adult↗

Establishment of Epstein-Barr virus-associated lymphoma cell line SUBL with t(2;3)(p11;q27) from a liver transplant patient.

A new lymphoma cell line, designated SUBL, was established from a Japanese patient with Epstein-Barr virus (EBV)-associated lymphoma, which developed during FK 506 therapy after liver transplantation. This cell line has undergone 80 passages over a period of 22 months. The cultured cells were positive for CD19, CD20, CD21, CD22, CD23, and HLA-DR, and negative for CD10 and surface immunoglobulins. Immunoglobulin gene analysis revealed rearrangements of JH and JK. T-cell antigens or T-cell receptor gene rearrangements were not observed on the cell line. The SUBL cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The EBV genome was detected in the original tissue and the cell line by the in situ hybridization method. These data indicate that this cell line represents the B-cell lineage at a pre-B-cell stage. SUBL cells showed successful heterotransplantation to mice with severe combined immunodeficiency (SCID). Chromosomal analysis revealed the karyotype 46,XY,t(2;3)(p11;q27). Molecular studies showed that c-myc, N-myc, and bcl-2 were not rearranged. This cell line will provide a useful in vitro system to study the relationship between chromosomal abnormalities and the activation of cellular oncogenes.

Animals↗