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Biomedical subjects

Y Tsuji

Publications and source records attributed to Y Tsuji.

At least 199 records · Page 11Linked to original sources

Metallothionein content increased in the liver of mice exposed to magnetic fields.

Although recent studies have shown that various stress can induce metallothionein (MT) synthesis in animal tissues, the induction of MT synthesis by exposure to static magnetic fields (SMF) has not been reported. We measured MT levels in the liver, kidney and brain of mice exposed to SMF and also evaluated the effect of SMF exposure on the induction of hepatic MT by treatment with carbon tetrachloride (CCl4). The MT content in the liver was significantly increased by exposure to 4.7 T of SMF for 6, 24, or 48 h, whereas that in the kidney or brain was not changed compared to the control. The combination of CCl4 injection and SMF exposure induced elevation of the hepatic MT content exceeding that induced by either treatment alone. These results indicate that exposure to the strong SMF induces MT synthesis in the liver in mice and enhances the hepatic MT synthesis induced by CCl4 administration.

Animals↗

Characterization of anti-sperm antibodies and their coding cDNA sequences by Epstein-Barr virus transformed B cell lines from lymphocytes of infertile women possessing anti-sperm antibodies.

Epstein-Barr virus (EBV)-transformed B cell lines that produce human antisperm antibodies were established using peripheral blood lymphocytes (PBLs) from infertile women with sperm immobilizing antibodies in their sera. We obtained three stable cell populations (designated B1, B2, D5) of transformed PBLs originating from three different patients. They produced IgM sperm-reacting antibodies directed against the tail of live, methanol-fixed and NaIO4-treated human spermatozoa. The established antisperm antibodies recognized noncarbohydrate sperm membrane antigens with different specificity and distribution in the male reproductive system. Antisperm antibody-B2 corresponding antigen appears to be specific for the male reproductive system. This antigen is excreted from the epithelial cells of the ductus epididymidis and bound to the spermatozoa in the lumen of the ductus. Antisperm antibodies B1 and D5 corresponding antigens were expressed on the spermatozoa in the seminiferous tubules and were common to the secretions of the ductus epididymidis, prostate and some other somatic organs. The cDNA of the immunoglobulin heavy chain genes were analyzed by reverse transcription polymerase chain reaction (RT-PCR) using RNA extracted from these clones. The immunoglobulin heavy chain cDNA sequences of these antisperm antibodies showed extremely high homology to previously reported immunoglobulin germline DNA sequences, implying that these antisperm antibodies might be natural autoantibodies rather than antibodies stimulated by external antigen.

Antibodies, Monoclonal↗

Endogenous tumor necrosis factor inhibits the cytotoxicity of exogenous tumor necrosis factor and adriamycin in pancreatic carcinoma cells.

Pancreatic carcinoma is one of the most devastating neoplasms with regard to its resistance to conventional therapy. In a previous report, we found that endogenous tumor necrosis factor (enTNF) exerts an intracellular protective effect against exogenous TNF- and Adriamycin (ADM)-induced cytotoxicity by scavenging oxygen free radicals (OFR) with induced manganous superoxide dismutase (MnSOD). We also know that glutathione S-transferase pi (GST-pi) and glutathione (GSH) also scavenge OFR. It remains unclear to what extent enTNF and MnSOD induced by enTNF regulate the sensitivity to ADM and exogenous TNF among different carcinoma cells. In this study, we examined the relationship between ADM and exogenous TNF sensitivity and en-TNF expression and MnSOD activity in four pancreatic carcinoma lines. We determined whether ADM and exogenous TNF sensitivity could be predicted by measuring enTNF expression and MnSOD activity in the carcinoma cells. The sensitivity to TNF and ADM varied with the cell lines, and TNF sensitivity correlated well with Adriamycin sensitivity. Moreover, enTNF expression and Mn-SOD activity correlated positively with resistance to ADM and exogenous TNF. When MIAPaCa-2 cells, which had the lowest enTNF expression and the highest sensitivity to exogenous TNF and ADM, were transfected with the nonsecretory-type human TNF gene (pTNF delta pro) to increase enTNF synthesis, their intracellular MnSOD activity and exogenous TNF and ADM resistance were increased. These findings suggest that MnSOD plays a critical role in scavenging OFR induced by ADM and exogenous TNF. enTNF is the most important factor that regulates the production of MnSOD. Therefore, it is plausible that inhibition of enTNF expression or MnSOD activity in pancreatic carcinoma would improve the efficacy of therapies for pancreatic carcinoma.

Doxorubicin↗

Nitric oxide donors increase cytosolic ionized calcium in cultured human intestinal epithelial cells.

We used fluorescence spectrophotometry, digital-imaging fluorescence microscopy, and the fluorescent dye, Fura-2, to measure the effects of several different nitric oxide (NO.) donors on intracellular levels of ionized calcium ([Ca2+]i) in cultured Caco-2BBe cells, a human enterocytic cell line. Incubation of Caco-2BBe cells with sodium nitroprusside (SNP) or isosorbide dinitrate for 2 h significantly increased [Ca2+]i. The effects of both agents were concentration dependent. The lowest concentrations of SNP or isosorbide dinitrate capable of increasing [Ca2+]i were .625 mM and 10 mM, respectively. Chelation of extracellular Ca2+ with 2 mM EGTA abrogated the increase in [Ca2+]i induced by SNP. In contrast, blockade of voltage-gated Ca2+ channels with 2 mM NiCl2 or 200 microM verapamil failed to affect SNP-induced alterations in [Ca2+]i. Using NBD-phallicidin to stain polymerized (F)-actin, we found that incubation of Caco-2BBe cells with SNP results in actin polymerization, particularly in the periphery of cells. We conclude that NO. increases [Ca2+]i and promotes actin polymerization in a cultured enterocytic cell line.

Caco-2 Cells↗

Primary prevention of HTLV-I in Japan.

The ATL prevention program (AAP) in the Nagasaki Prefecture since 1987 consists of screening of pregnant women and asking the seropositives to refrain from breast-feeding. We screened approximately 90% of gravidas in the Prefecture and > 90% of the seropositive women agreed not to breast-feed. The maternal transmission rate dropped from approximately 20% to approximately 3%. PCR of cord bloods showed that 2.5% were PCR-positive. However, among formula-fed children, none of the cord-positives seroconverted, and none of the seropositives tested had been cord-positive. Breast-feeding for less than six months decreased the transmission rate significantly, but may have a higher transmission rate than the formula feeding.

Adolescent↗

Serological study of Bartonella henselae in cat scratch disease in Japan.

It has become clear that Bartonella henselae is a common cause of cat scratch disease (CSD). The indirect fluorescence antibody (IFA) test for detection of IgG and IgM antibodies to B. henselae concerning CSD showed that 5 (50%) of 10 patients with CSD had a serum IgG antibody titer of 1:128 or more and that 2 (20%) patients had a serum IgM antibody titer of 1:20 or more. One of 7 asymptomatic members of patients' families (14%) had IgG antibody to B. henselae at a titer of 1:256. IgM antibody to B. henselae was not detected in sera from the patients' families. Both IgG and IgM antibodies to B. henselae were not detected in sera from the healthy control group. These data suggest that B. henselae may be a cause of CSD in Japan.

Adult↗

Detection of K-ras point mutations at codon 12 in pancreatic juice for the diagnosis of pancreatic cancer by hybridization protection assay: a simple method for the determination of the types of point mutation.

The present study was undertaken to detect K-ras oncogene point mutations at codon 12 in pure pancreatic juice (PPJ) by the hybridization protection assay (HPA) method for the diagnosis of pancreatic cancer (PC). This assay can be carried out within 30 min and can determine not only the presence of a mutation, but also the mutational type of K-ras at codon 12. The minimal ratio of mutant DNA detectable by the HPA was 5-10% of the total DNA. PPJ was collected through a cannula under duodenal fiberscope control from 20 patients with PC and 20 patients with chronic pancreatitis (CP). Analysis of PPJ by the HPA revealed that the incidence of K-ras point mutations at codon 12 was 55% (11/20) in patients with PC and 0% (0/20) in those with CP. Mutational types of K-ras at codon 12 in PC were aspartic acid (Asp) in nine cases, both Asp and cysteine in one case, and arginine in one case. Analysis of K-ras point mutations at codon 12 in PPJ using the HPA method seems promising as a new genetic test for the diagnosis of PC, because the HPA method is simple, and can easily determine the mutational type.

Base Sequence↗

Portal-systemic shunting in a patient with normal portal vain pressures and histological evidence of idiopathic portal hypertension.

Although idiopathic portal hypertension (IPH) is clinically characterized by portal hypertension and marked splenomegaly, we have experienced a case of spontaneous portal-systemic shunt without splenomegaly in whom the liver histology resembled IPH but with normal portal pressure. We admitted a 64 year old man who had suffered from hepatic encephalopathy for 2 years. Laparoscopy revealed a dark grey liver with a sharp edge and a concave surface. Examination of a liver biopsy specimen revealed peri-portal fibrosis consistent with IPH. A single, large, portal-systemic shunt was identified by percutaneous transhepatic portography. The shunt arose from the left gastric vein and flowed through the left renal vein into the inferior vena cava. No varices were identified. There were no morphological changes in the hepatic or portal veins. Portal vain pressure was normal. There was a slight difference between the portal pressure and the wedged hepatic vein pressure, suggesting a presinusoidal block. This case raises important questions concerning the aetiology of IPH and the relationship between portal hypertension and the development of collateral venous circulation.

Collateral Circulation↗

Pharmaceutical properties of freeze-dried formulations of egg albumin, several drugs and olive oil.

The freeze-dried ternary formulations of meclizine (MZ, an anti-motion sickness drug), prednisolone (PRED, an anti-inflammatory drug) and norfloxacin (NFLX, an anti-microbial drug) which are poorly water-soluble and are low bioavailability drugs, were prepared using egg albumin and olive oil. The powder X-ray diffractions, the dissolution rate and the bioavailabilities in vivo of these formulations were studied in comparison with each drug alone. By forming ternary formulations of these drugs, the dissolution rates of the drugs from the formulations were significantly improved compared with each drug alone. The results of their powder X-ray diffraction measurements showed that these drugs in the ternary formulations presented in an amorphous form, indicating increased dissolution rates. On the other hand, the plasma concentrations of these drugs increased significantly after oral administration in formulations to rats, except for the NFLX formulation, and the areas under the concentration-time curves (AUC) of the ternary formulations of MZ, PRED and NFLX were 2.1, 1.6 and 1.3 times those of the drugs alone, respectively. From these results, it was proven that formulations consisting of egg albumin, olive oil and poorly water-soluble drugs were useful preparations for improving the drug's disadvantageous pharmaceutical properties.

Administration, Oral↗

Osteogenic action of parathyroid hormone-related peptide (1-141) in rat ROS cells.

To examine the autocrine/paracrine effect of parathyroid hormone-related peptide (PTHrP) on osteoblast function, the entire coding region of rat PTHrP (1-141) cDNA inserted into the expression vector was stably transfected into the rat clonal strain of the osteoblast-like cell, ROS 17/2.8, and established stable transfectants. Using the PTHrP-overexpressing ROS cells (ROS/PLP/6), we analyzed in vitro cell characterization and in vivo osteogenic properties. As expected, overexpression of endogenous PTHrP in vitro induced PTH/PTHrP receptor down-regulation confirmed by Northern blots, receptor binding assays, and functional analysis. The established transfectants indicated a decreased growth rate compared with the original non-transfected ROS 17/2.8. Although cAMP production induced by exogenous PTH was suppressed in ROS/PLP/6, the stimulatory effects of forskolin and chorela toxin showed no significant difference between the original ROS 17/2.8 and transfected cells, but the in vivo osteogenic properties were histologically potentiated in transfectants with increased bone matrix and acceleration of mineralization within tumors. The levels of osteocalcin and osteopontin mRNAs were also increased in transfectants. The down-regulated in vitro PTH/PTHrP receptor mRNA was restored in in vivo tumor tissues. Our study provides clear evidence that the in vivo osteogenic function in ROS cells is potentiated by PTHrP, through an autocrine/paracrine mode of action.

Animals↗

The effects of a 4.7 tesla static magnetic field on the frequency of micronucleated cells induced by mitomycin C.

The effects of a 4.7 tesla (T) static magnetic field (SMF) on the frequency of micronucleated cells (MN-cells) in CHL/IU cells induced by mitomycin C (MMC) were studied in vitro. Exposure to a 4.7 T SMF for 6 hr significantly decreased the frequency of MMC-induced MN-cells for expression culture periods of 18, 42, 54 and 66 hr. The highest frequency of MMC-induced MN-cells was observed at the expression culture period of 42 hr and decreased gradually in the same manner in both exposed and control groups. These results suggest that a 4.7 T SMF may exert on influence during the DNA damage stage produced by MMC rather than on the formation of micronuclei during the stage following MMC-induced DNA damage.

Animals↗

Five-tesla static magnetic fields suppress food and water consumption and weight gain in mice.

In this study, the effects of 5-tesla (T) static magnetic fields (SMFs) on food and water intake in BALB/c mice were examined. We also examined body weight changes, organ weights and some serum biochemical parameters to evaluate the physiological changes resulting from changes in food and water intake. Mice were exposed to 5-T SMFs for 24 h and 48 h. Food intake, water intake and the mean body weight of mice tended to decrease after 24 h of exposure to SMFs (p = 0.054, p = 0.119, p = 0.107, respectively). Those parameters decreased significantly after 48 h of exposure (p = 0.039, p = 0.0003, p = 0.009, respectively). These results suggested a positive relationship between the duration of exposure, and the responses, represented by food intake, water intake, and body weight of the mice. However, the weights of brain, lungs, heart, liver, spleen, and kidneys did not change after 48 h of exposure. The blood urea nitrogen (BUN) levels and blood glucose levels increased significantly after 48 h of exposure (p = 0.03, p = 0.005, respectively). The BUN-to-creatinine (BUN/Cr) ratio tended to increase after 48 h of exposure (p = 0.07). We conclude that exposure to 5-T SMFs for 48 h suppresses eating and drinking behavior. We considered that the decreased body weight, increased BUN levels and slightly increased BUN/Cr ratio after 48 h of exposure to 5-T SMFs were due to body fluid loss resulting from decreased food and water intake.

Animals↗

Upper urinary tract involvement after cystectomy and ileal conduit diversion for primary bladder carcinoma.

OBJECTIVES: To design a proper follow-up for cystectomy and ileal conduit urinary diversion for primary bladder transitional carcinoma, we compared the radiographic characteristics of recurrent malignant upper tract lesions with those of benign ureteroileal anastomosis strictures. METHODS: Over a 20-year period, we followed 61 patients who underwent cystectomy and ileal conduit diversion at our hospitals for a minimum period of 3 years. Excretory urography was performed routinely at 1, 3, 6 and 12 months after cystectomy and once yearly thereafter. RESULTS: Five patients (8.2%) developed malignant ureteral obstruction (4 had metachronous upper tract tumors, and 1 patient had retroperitoneal lymph node metastasis which compressed the ureter). Eleven patients (18.0%) developed benign ureteroileal anastomotic stricture. The interval between cystectomy and initial detection of the malignant and benign upper tract lesion ranged between 34 and 118 months (mean 69 months) and between 1 and 20 months (mean 5.1 months), respectively. In all patients with malignant upper tract obstruction, a complete loss of renal function occurred within 10 months after the detection. Conversely, a progressive renal dysfunction was observed in patients with benign ureteroileal anastomotic stricture. All patients were asymptomatic before the detection of lesions on excretory pyelography. CONCLUSIONS: Our results suggest that cancer recurrence can occur even 10 years after cystectomy, typically progressing very rapidly within 1 year. A benign ureteroileal anastomotic stricture, on the other hand, tends to occur within 2 years but advances slowly. Consequently, a proper follow-up necessitates annual excretory urography and/or renal ultrasonography in all patients with ileal conduit urinary diversion after cystectomy.

Adult↗

Endoscopic trigonoplasty in pediatric patients with primary vesicoureteral reflux: preliminary report.

PURPOSE: We investigated the preliminary surgical results of endoscopic trigonoplasty in pediatric patients with primary vesicoureteral reflux. MATERIALS AND METHODS: We performed endoscopic trigonoplasty in 6 pediatric patients (11 refluxing ureters). Reflux was grade II in 4 reno-ureteral units, grade III in 5, grade IV in 1 and grade V in 1 (international classification). Surgery was done using laparoscopic and endoscopic instruments. RESULTS: Vesicoureteral reflux disappeared 3 to 12 months postoperatively. Analgesics were administered postoperatively to 4 patients for 24 hours and to 2 for 48 hours. No bladder irritability or postoperative upper urinary tract dilatation was observed in the early postoperative period. CONCLUSIONS: Minimally invasive endoscopic trigonoplasty can be an effective surgical procedure for pediatric patients with vesicoureteral reflux.

Child↗

Suppression of glucocorticoid-induced thymocyte apoptosis by co-culture with thymic epithelial cells.

There are many reports concerning glucocorticoid-induced thymocyte apoptosis, but little is known about the participation of thymic stromal cells, especially the thymic epithelial (TE) cells, in the apoptosis. In this study, we investigated the in vitro effect of TE cells on dexamethasone-induced DNA fragmentation of thymocytes as a parameter for apoptosis. By co-culture of thymocytes with TE cell line, at the condition without cell-cell contact, the DNA fragmentation of thymocytes caused by physiological level of glucocorticoid was significantly suppressed. Same effect was detected when treated the thymocytes with the supernatant from the cultures of TE cell line. These results suggest that the humoral factors released from TE cells rescue the thymocytes from the glucocorticoid-induced apoptosis. Chemical and physico-chemical nature of the factors are discussed.

Animals↗

[The preventive effect of weekly high-dose 5-FU infusion (WHF) after resection of hepatic metastasis from colorectal cancer].

Hepatic metastasis is often found even after resection of hepatic metastases from colorectal cancer. This implies that the micrometastasis already existed in residual liver when the resection was performed, and so complete recovery with resection alone is rare. We have been using a weekly high-dose 5-FU HAI (WHF = 5-FU 1,000 mg/m2/5 hrs/qw) since 1991, which has preventive effects for metastasis in residual liver as compared to a group treated without infusion chemotherapy. Hepatectomy was performed in 30 of 113 cases of hepatic metastasis from colorectal cancer during the past 16 years. For comparison, we divided the 30 cases into group A1 (16 cases H1:12, H2:4), which received hepatectomy only, and group A2 (14 cases H1:8, H2:4, H3:2), which additionally received infusion chemotherapy. The 1- and 3-year (cumulative) survival rates were 64.6% and 32.3% in group A1, and 100% and 75.3% in group A2 respectively in which the treatment outcome was significantly higher. The 1- and 3-year recurrence rates were 41.7 and 66.3 in group A1, and 8.3% each in group A2, respectively, which reveals that metastasis in residual liver was controlled in group A2. Other metastases were seen in lung (6 cases), bone (2 cases), hepatic hilar lymph node (3 cases), brain (1 case) and local (3 cases) in group A1, while only one metastasis in each brain and locally was seen in group A2 so far. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect not only for the recurrence in residual liver but also for other metastases. Therefore, as improvement in the survival rate is expected.

Aged↗

[A case of non-resectable pancreatic cancer surviving more than 4 years by intra-arterial infusion chemotherapy with angiotensin-II].

This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case.

Angiotensin II↗