Biomedical subjects
Publications and source records attributed to Y Kondo.
We evaluated the influence of the head model on biomagnetic source localization by utilizing a computer simulation. We localized the source of a magnetic field that was calculated using a realistic head model, and then evaluated the localization errors. It was seen that the sphere model adequately localized the dipole in cases near the sensor, but not in cases where the dipole was deeply situated.
Changes in muscarinic acetylcholine receptor (mACh-R) binding and muscarinic cholinergic m1 receptor (m1-R) mRNA levels were determined in a rat model of cerebral hypoperfusion in which hypoperfusion was induced by permanent bilateral occlusion of the common carotid arteries. After 6 weeks of hypoperfusion, mACh-R binding activity was significantly reduced in the frontal cortex (79.0 percent, P <0.01), striatum (74.2 percent, P < 0.01) and hippocampus (78.6 percent, P < 0.01), and the m1-R mRNA levels in the frontal cortex (86.6 percent, P < 0.05) and striatum (89.4 percent, P < 0.05) compared with sham-operated control. Repeated administration of bifemelane hydrochloride (15 mg/kg/day, p.o., once a day from the day of operation for 6 weeks) prevented the hypoperfusion-induced loss of mACh-R binding and m1-R mRNA levels above described. Since the central cholinergic systems play an important role in learning and memory, these findings suggest that bifemelane hydrochloride is useful to treat and/or prevent vascular dementia which is closely related to cerebral hypoperfusion.
The distribution of carnitine was investigated in male Wistar rats with sepsis or acute liver failure. Sepsis was produced by cecal ligation and puncture, while acute liver failure was induced by intraperitoneal injection of carbon tetrachloride. Then 14C-carnitine or L-carnitine was injected intravenously. In healthy control rats and rats with sepsis, both 14C-radioactivity and carnitine were increased in the liver and kidneys. When the carnitine fractions were investigated, it was found that free carnitine and short-chain acylcarnitine were increased. In the rats with acute liver failure, 14C-radioactivity decreased in the liver, but carnitine increased, with free carnitine and short-chain acylcarnitine levels rising. These findings suggested that exogenous free carnitine accumulated directly in the organs with carnitine deficiency in rats with sepsis and acute liver failure. In addition, there was differential regulation of the fractions of both exogenous and endogenous carnitine (free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine). Furthermore, the distribution of exogenous carnitine differed between sepsis and acute liver failure.
The overexpression of the multidrug resistance (mdr1) gene and its product, P-glycoprotein (P-gp), is thought to limit the successful chemotherapy of human tumours. The mechanism by which mdr1 gene and P-gp are overexpressed in human tumours, however, is not yet clear. In this report, we show that the mdm2 (murine double minute 2) gene induced the expression of the mdr1 gene and P-gp in human glioblastoma U87-MG cells, which did not express the MDM2 protein or P-gp. The mdm2 gene, in addition, conferred the resistance of U87-MG cells to the apoptotic cell death induced by etoposide (VP-16) or doxorubicin. Furthermore, treatment with mdm2 antisense oligonucleotides inhibited the expression of P-gp in MDM2-expressing U87-MG cells. These findings suggest that the mdm2 gene may play an important role in the development of MDR phenotype in human tumours.
Apoptosis (programmed cell death) is an essential physiological process that is genetically regulated and contributes to the balance between cell growth, differentiation, and the maintenance of normal cells. Recent studies show that deprivation of growth factor induces apoptosis in endothelial cells. However, the molecular mechanisms regulating apoptosis remain unclear. In this study, we demonstrate that deprivation of basic fibroblast growth factor (bFGF) increased the expression of interleukin-1 beta-converting enzyme (ICE) protein, and subsequently induced apoptosis in murine aortic endothelial (MAE) cells. In contrast, the proteins of the tumor suppressor p53 and c-myc were undetected during apoptosis. This apoptosis was suppressed by the tetrapeptide ICE inhibitor, Ac-YVAD-CMK. Overexpression of murine ICE, in addition, induced apoptosis in MAE cells using gene transfer techniques. These results strongly suggest that ICE may mediate apoptosis in bFGF-deprived endothelial cells, and the suppression of ICE function could represent a novel approach for the protection of endothelial cells from damages.-Kondo, S., Kondo, Y., Yin, D., Barnett, G. H., Kaakaji, R., Peterson, J. W., Morimura, T., Kubo, H., Takeuchi, J., Barna, B. P. Involvement of interleukin-1 beta converting enzyme in apoptosis of bFGF-deprived murine aortic endothelial cells.
Decreased skin reactions using five kinds of recall antigens correlate d with the stage of colorectal cancer. Immunosuppressive factors in the serum (IS index) increased with the progression of the stage in cancer patients, but interleukin (IL)-I and IL-2 production in peripheral mononuclear cells (PBMC) did not correlate with the advance of the disease. In patients with low immunosuppressive factors, the score of skin reactions was significantly higher than that in patients with high immunosuppressive factors. Increased serum immunosuppressive factors seem to reduce skin reactions in the patients. Furthermore, significant difference in skin reaction score was observed between patients with high IL-1 production of PBMC and patients with low IL-1 production of PBMC. These results suggest that skin reaction might be controlled by serum immunosuppressive factors and IL-1 production of PBMC, and that the score of skin reaction using multirecall antigens is a useful parameter to learn the host immunity in colorectal cancer.
OBJECTIVE: The authors evaluated the rationale for and feasibility of gastroduodenal artery preservation in pylorus-preserving pancreatoduodenectomy (PPPD) for periampullary cancer in which the pancreatic remnant maintains a normal function and morphologic characteristics. SUMMARY BACKGROUND DATA: Pylorus-preserving pancreatoduodenectomy has become one of the standard treatments used for benign and malignant diseases of the pancreatoduodenal region, surpassing ordinary pancreatoduodenectomy in terms of technical ease, mortality rate, and postoperative nutrition. Pylorus-preserving pancreatoduodenectomy is usually associated with gastroduodenal artery division, which presents potential risks of insufficient duodenal vascularity and lethal postoperative bleeding from the gastroduodenal artery stump. The latter complication particularly occurs after resection of bile duct or ampullary cancer in a patient whose pancreas remains functionally and morphologically normal to have much more pancreatic secretion than the fibrotic pancreas seen in pancreatic cancer. According to the authors data on the volume of secretion from the residual pancreas via a stent tube after pancreatoduodenectomy, the sclerotic pancreas, as seen in cancer of the pancreatic head, secrets only 20 to 50 mL/day, whereas the secretion from the soft pancreas, as seen in bile duct cancer, amounts to 300 to 600 mL/day, even during the period of nothing by mouth. METHODS: Retrospectively, we made a histopathologic study of eight specimens of distal bile duct and ampullary cancer resected by pancreatoduodenectomy or PPPD with gastroduodenal artery division. Prospectively, we performed gastroduodenal artery- preserving PPPD for 10 patients with distal bile duct, ampullary, and islet cell cancers. RESULTS: The histopathologic study revealed no invasion or metastasis around the gastroduodenal artery. Clinical application of gastroduodenal artery-preserving PPPD showed no technical difficulty, and neither severe complications nor recurrence around the gastroduodenal artery were observed for up to 22 months after surgery. CONCLUSIONS: Gastroduodenal artery- preserving PPPD might be recommended as a safe procedure for patients who have a functionally and morphologically normal pancreas.
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We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of (131)I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. (131)I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of (131)I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of (131)I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus (131)I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer.
Fifteen of 353 environmental isolates of lactic acid bacteria consistently showed activity against Listeria monocytogenes, Streptococcus mutans, Actinomyces viscosus, and/or Propionibacterium acnes. Strain T140, isolated from the surface of Japanese pampas grass leaves and identified as Lactobacillus salivarius subsp. salicinius, also had activity against several Lactobacillus species, Staphylococcus aureus and Yersinia enterocolitica. Since the antagonistic factor(s) produced by T140 was sensitive to a proteolytic enzyme, it was concluded that a bacteriocin (named salivacin 140) was involved in the inhibition activity. Strain T140 required a high initial pH (7.5-8.5) in agar plates for bacteriocin production.
Isaria japonica YASUDA was cultured in a liquid medium, and its culture fluid (IJCE) was tested for stimulatory activity to humoral antibody production. IJCE significantly enhanced the production of anti-sheep red blood cell (SRBC) plaque forming cells (PFC) by oral ingestions at 10 and 30 mg/kg/d for 4 consecutive days, either before or after SRBC challenge. It also recovered the reduction of anti-SRBC PFC response and number of spleen cells caused by treatment with 5-fluorouracil. It is suggested that IJCE is a promising source for an immunomodulating tool or medicine.
We compared immunoglobulin G (IgG) preparations obtained from untreated Graves' patients with those from Graves' patients in remission and normal subjects in terms of their activity to stimulate the phospholipase C-Ca2+ signaling. Ca2+ mobilizing activity of the untreated Graves' IgG preparations in FRTL-5 thyroid cells was statistically (P < 0.01) and significantly higher than the activity of normal IgG preparations, whereas there was no significant difference in the activity between the remission Graves' and normal IgG preparations. Digital video imaging of fura2-loaded FRTL-5 cells confirmed that the Ca2+ mobilizing action of the untreated Graves' IgG preparations is an intracellular event. Phospholipase C activation by the untreated but not remission Graves' IgG preparations was statistically higher than that by normal IgG preparations. Involvement of the phospholipase C activation in the Ca2+ response mechanism was confirmed by the enhancement of the Ca2+ response by an adenosine derivative, N6(L-2-phenylisopropyl)adenosine (PIA) which can potentiate agonist-induced phospholipase C activation but not the Ca2+ mobilization itself. The Ca2+ response to the IgG preparations did not show a significant correlation with their cAMP response (TSAb). Therefore, the Ca2+ response to Graves' IgG preparations may be utilized as a functional marker for Graves' disease in addition to TSAb.
In order to establish the genetic profiles of three inbred strains of rats (MITB/Yag, MITC/Yag and MITE/Yag; commonly designated as Mitake strains), which were derived from wild specimens of the Rattus norvegicus trapped in Mitake-cho, Gifu, Japan, 63 microsatellite markers were typed in these strains as well as nine other laboratory inbred strains. The data indicate that the MITB and MITC strains are very closely related (3% polymorphism between these strains), whereas the third strain MITE/Yag is relatively different from the other two strains (36% with the MITB, 39% with the MITC). Eighty-three to 58% of polymorphic loci had different alleles between the Mitake strains and the other strains, but 65-35% between the latter strains. In addition, 14 new alleles were found in the Mitake strains. These results suggest that the Mitake strains are useful for linkage analysis.
Endoscopic sinus surgery (ESS) was compared with Caldwell-Luc (C-L) operation based on blood loss during surgery, operation time, period of hospitalization and complications. Both blood loss and operation time were significantly reduced in ESS as compared with C-L operation. In addition, patients undergoing ESS resulted in discharges after surgery earlier than those undergoing C-L operation. Minor complication was seen in 4.8% of the ESS patients whereas no major complication was recognized. ESS is a relatively safe procedure with superiority over C-L operation.
Higher order DNA fragmentation may be an essential signal in apoptosis. We found that etoposide (VP-16) induced apoptosis in human DU-145 prostatic carcinoma cells in a time- and concentration-dependent manner. Chromatin condensation was morphologically evident only when cells detached from the monolayer; untreated or VP-16-treated attached cells retained a normal morphology. We describe a radiolabeled alu-I sequence-based quantitative field inversion gel electrophoresis (QFIGE) method that permitted observation and quantification of discrete high molecular weight DNA fragments in detached (apoptotic) and attached (preapoptotic) DU-145 cells. The DNA fragments generated during the apoptotic death of these cells were > or = 1 (mega-base pairs) mbp, 450-600 (kilo-base pairs) kbp, and 30-50 kbp; we observed that these DNA fragments increased 9 +/- 2-, 8 +/- 2-, and 25 +/- 11-fold versus control, respectively, with a 24-hr exposure to 30 microM VP-16 in attached cell populations. In detached VP-16-treated cells, there was accrual of 30-50-kbp DNA fragments with a concomitant loss of the > or = 1-mbp and 450-600-kbp fragments; internucleosomal DNA cleavage was never observed. This pattern of high molecular weight DNA fragmentation was inhibited by cycloheximide treatment and was common to other apoptotic agents, including melphalan and bleomycin. These findings suggest that the > or = 1-mbp and 450-600-kbp DNA fragments are products of endonuclease activation and are not topoisomerase II/DNA interactions. Finally, the generation of the 30-50-kbp DNA fragments may mediate chromatin condensation, which characterizes apoptosis.
Cell proliferation has a crucial importance in biologic potentialities of tumor cells. Several methods to measure S-phase fraction in tumor samples have been developed, with considerable limitations in practical applications. Histones are nucleosomal proteins that are responsible for packaging chromosomal DNA into nucleosomes. The expression of histone genes is a fundamental step constituting the process of cell proliferation. Because histone H3 mRNA accumulates in the cytoplasm during S-phase, and then decreases as cells approach G2-phase, demonstration of histone H3 mRNA expression in a tumor cell population may represent responsible S-phase fraction. Thus, we have assessed S-phase fraction by nonisotopic in situ hybridization for histone H3 mRNA in paraffin sections of hepatocellular carcinomas (HCCs); then, we compared this with the histologic grades and other cell proliferative markers. In contrast to radioisotopic detection, signals were distinctly visualized, and quantitation of the stained-cells was easily carried out. Histone H3 labeling index (LI) significantly correlated with other cell proliferative markers, including Ki-67 (MIB-1) and PCNA immunostainings, and mitotic index. In addition, a statistically significant correlation was seen between histone H3 LI and histologic grades of differentiation, i.e., histone H3 LI being higher in less-differentiated HCCs. Furthermore, histone H3 LI/Ki-67 LI ratio was significantly higher in the moderately and poorly differentiated subtypes (including one case of the undifferentiated subtype) than in well-differentiated HCCs. By using this nonisotopic in situ hybridization technique, it becomes possible to assess rapidly, retrospectively, safety, and easily a malignant potentiality of HCCs in paraffin-embedded tissues.
A 61-year-old male was admitted after detecting gastric lesion by gastrography in a medical health examination. The patient was diagnosed as Borrmann 2 advanced gastric cancer with remarkable intraperitoneal lymph node metastasis and liver tumor of lateral segment. Relative non-curative gastrectomy was performed with combined partial hepatectomy. The liver tumor measured 1.5 x 1.5 cm and was intraoperatively diagnosed as metastasis of gastric cancer. Mitomycin C 26 mg was given intravenously on the day of operation and 5-fluorouracil (5-FU) 150 mg/day orally since postoperative 14th day as adjuvant chemotherapy. The administration of 5-FU was continued for 5 years. As a result of such combination therapy, the patient still has had no recurrence 8 years following operation.
To evaluate the efficacy of adjuvant immunochemotherapy, especially the long-term administration of HCFU to patients with noncuratively resected and unresected gastric cancer, a randomized controlled study was conducted by 16 institutions in Hokkaido. After surgery, 185 patients were divided into two groups using the envelope method; group A (84 patients) treated by MMC (4 mg, twice a week, total 1 mg/kg)+OK-432 (or PSK): group B (101 patients) treated with MMC+OK-432+HCFU (600 mg, per day). The 5- and 10-year survival rates were 9.8 and 3.1% in group A, and 11.1 and 11.1% in group B (p=0.062). Better survival rates were obtained in those cases with unresected, S3, or peritoneal dissemination in group B. These results suggested the long-term administration of HCFU was effective for noncuratively resected and unresected gastric cancer.