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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 307 records · Page 17Linked to original sources

Biliary interleukin 6 levels as indicators of hepatic allograft rejection in rats.

Interleukin 6 has recently been noted to be present during the rejection response to grafted organs. In this study, we investigated biliary and serum interleukin 6 levels following liver transplantation in rats. IL-6 levels in bile and serum of naive rats were below 0.6 U/ml and 0.5 +/- 0.2 U/ml (mean +/- SD), respectively. Both biliary and serum IL-6 levels showed high values (greater than 10.0 U/ml and greater than 1.6 U/ml, respectively) on the day after transplantation, which seemed to reflect the inflammatory status caused by the surgical stress. Later samplings showed that the kinetics of serum IL-6 differed among the animals without any definite feature related to graft rejection. In contrast, biliary IL-6 levels correlated well with the severity of the rejection response as determined histologically. Biliary IL-6 levels started to rise at the onset of the rejection response (6.6 +/- 0.6 U/ml), increased further with its progression (19.3 +/- 7.8 U/ml), and then finally fell in the terminal stage (less than 2.0 U/ml). Elevation of biliary IL-6 was observed at an early stage when abnormalities could be detected histologically but not in liver function tests and bile flow. Therefore, biliary IL-6 levels may be of value for the early diagnosis of rejection following liver transplantation.

Animals↗

Human lung cancer cell line producing hepatocyte growth factor/scatter factor.

Hepatocyte growth factor (HGF)/scatter factor (SF) is a cytokine which is produced by mesenchymal cells and stimulates the motility of some epithelial cells, including cancer cells and vascular endothelial cells. Two human lung cancer cell lines, PC-1 and PC-13, were found to produce a protein which was indistinguishable from HGF/SF with regard to biological activities and immunological characteristics, although they were derived from epithelial cells. In general, highly aggressive cancer cells often show some mesenchymal characteristics, and production of HGF/SF by cancer cells is also considered as a phenomenon of acquisition of mesenchymal phenotype, which may be involved in cancer invasion and progression. These cell lines showed no apparent response to exogenous HGF/SF. In addition, no c-met proto-oncogene product was detectable in these cells by Western blot analysis. Although the function of HGF/SF produced by cancer cells, either autocrine or paracrine stimulation, remains to be studied, this is the first report to describe cancer cells producing HGF/SF.

Blotting, Western↗

Phase plane plot of electrograms as a marker of ventricular electrical instability during acute ischemia: initial experimental results and potential clinical applications.

We used a phase plane plots method (a plot of voltage [V(t)] vs rate of change of voltage [dV/dt]) derived from nonlinear dynamics to transform a sinus rhythm strip into a geometric form. The geometric form thus obtained detects variations in the ECG over time and therefore may aid in identifying patterns of vulnerability to ventricular fibrillation (VF). The trajectories of consecutive ventricular depolarizations and repolarizations of sinus rhythm in dogs that evolve to VF showed characteristic differential band thickening (inhomogeneities) that were absent in the dogs that did not develop VF. This method of analysis can be a useful complementary tool to detect cardiac electrical instability, and with simple hardware, can easily be displayed in real time.

Animals↗

Increased temporo-spatial dispersion of repolarization during double premature stimulation in the intact ventricle.

The degree of temporo-spatial variation of repolarization during single (S2) and double (S3) premature stimulation was evaluated in five closed-chest anesthetized dogs. Monophasic action potentials (MAP) were simultaneously recorded with contact electrode and MAP duration (MAPD) restitution curves constructed from right ventricular (RV) and left ventricular (LV) endocardial sites. At a given coupling interval, S3 was associated with significantly greater dispersion of MAPD then S2 (spatial dispersion, i.e., between RV and LV). Similarly, at a given diastolic interval, S3 at RV and LV sites, was associated with significantly greater dispersion of MAPD then S2 (temporal dispersion). It is concluded that S3 is associated with greater temporo-spatial dispersion of repolarization then S2.

Action Potentials↗

[Urodynamic findings in patients with a urethral Kock pouch after radical cystectomy].

Urodynamic evaluation was performed in 11 male patients, who underwent radical cystectomy with pelvic lymph node dissection for bladder cancer followed by bladder replacement with a urethral Kock pouch, 3 to 21 months after the operation. Frequency of micturition were 4.9 +/- 1.5 times (mean +/- S.D.) during the day-time and 1.5 +/- 1.2 times during the night-time. Tidal volume of micturition ranged from 300 to 550 ml and residual volume from 10 to 30 ml. Urinary continence was completely preserved in all patients (100%) during the day-time and 8 (72.7%) during the night-time. On pouchmetry, maximum capacity of the pouch was 429.2 +/- 82.4 ml, and intra-pouch pressure was 16.2 +/- 5.4 cmH2O at the capacity of 200 ml and 38.7 +/- 11.5 cmH2O at the maximum capacity. Maximum intra-pouch pressure on voiding was 80.0 +/- 19.4 cmH2O. Uroflowmetry demonstrated intermittent voiding curves in all the patients, with maximum flow rate of 15.2 +/- 6.5 ml/sec, voided volume of 405.9 +/- 80.7 ml and residual rate of 4.5 +/- 2.6%. Maximum intra-urethral pressure at the external urethral sphincter was 28.0 +/- 11.3 cmH2O when the pouch was empty and increased in response to pouch filling up to 64.7 +/- 27.0 cmH2O. Maximum urethral closing pressure and total profile length on the urethral pressure profile were 30.2 +/- 12.4 cmH2O and 20.9 +/- 9.0 mm, respectively, with the pouch empty, and 23.2 +/- 14.5 cmH2O and 20.0 +/- 7.6 mm, respectively, with the pouch full.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Results in treatment of urinary incontinence in the elderly].

The diagnosis and treatment of urinary incontinence in the elderly out-clinic patients were reviewed. Sixty-three patients (24 males and 39 females) over 60 years old, who consulted our clinic complaining urinary incontinence, were subjected to the present study. The patients' ages ranged from 60 to 91, with the mean age of 72.9 years old. The types of the incontinence were urge in 44 cases (69.8%), stress in 10 (15.9%), outflow in 5 (7.9%) and mixture of urge and stress in 4 (6.4%). Urge incontinence resulted from unstable bladder in 63.6% and from neurogenic bladder (overactive detrusor) in 36.4%. Cerebrovascular diseases were the most common cause of the neurogenic bladder. Fifty-four patients (85.7%) were out-patients and 9 (14.3%) were hospitalized for other diseases. Thirteen patients (20.6%) with dementia were included. Diagnosis was made on the basis of a detailed questionnaire, physical examination and voiding chart, and confirmed by urodynamic study. Treatment was positively made by means of drug therapy, operation, clean intermittent catheterization and/or behavior training. As results, incontinence disappeared in 52.4% (frequency of incontinence/day: 5.0 +/- 2.6 times/day to 0), was fairly improved in 30.2% (5.1 +/- 2.3 to 1.2 +/- 0.8), was slightly improved in 7.9% (3.4 +/- 1.4 to 2.4 +/- 1.4) and unchanged in 9.5% (8.2 +/- 2.3 to 8.3 +/- 2.2). Severe neurogenic bladder (overactive), dementia and physical disability were proposed to be important factors responsible for treatment failure. Aggressive therapy should be tried to treat the urinary incontinence in the elderly, since favourable results can be expected in most of the cases.

Aged↗

[The efficacy of transarterial immuno-embolization therapy in patients with hepatocellular carcinoma].

The efficacy of transarterial immuno-embolization therapy (TIE) was investigated in 7 patients with multiple hepatocellular carcinoma (HCC). We administered OK-432 (10 KE), fibrinogen (30 mg/ml) and thrombin (1 U/ml) as a new treatment for HCC with intrahepatic metastasis. In all patients with a high level of AFP, the AFP level decreased promptly less than the pretreatment level after TIE therapy. High fever in all cases, epigastralgia in 6 cases and appetite loss in 3 cases were observed after TIE therapy. Our results indicate that this therapy may be a safe and effective method in HCC patients with intrahepatic metastasis.

Administration, Oral↗

Mechanism of extracellular ATP-stimulated phosphoinositide hydrolysis in rat glioma C6 cells.

In rat glioma C6 cells, extracellular ATP stimulated phosphoinositide (PI) hydrolysis in concentration- and time-dependent manners with a median effective dose value of 60 microM. The maximal response was attained at 300 microM ATP. Of adenine nucleotides, ATP and adenosine 5'-O-(3-thiotriphosphate) were most effective, while adenosine, AMP and beta,gamma-methylene ATP were ineffective. Similar results were obtained in cultured rat astrocytes. The stimulatory effects of ATP and ADP were negated by removal of external Ca++ in C6 cells. ATP at 300 microM induced an elevation of intracellular Ca++ concentration in 1-[2-(5-carboxyoxazol-2-yl)-6-amino-benzofuran-5-oxy]-2-(2'-amino- 5'- methylphenoxy)-ethane-N,N,N',N' acid-loaded C6 cells. This response was not blocked by nifedipine (10 microM) and verapamil (10 microM). A Ca++ ionophore A23187 (10 microM) stimulated PI hydrolysis in C6 cells. The responses to ATP (300 microM) and A23187 (10 microM) were additive. In digitonin-permeabilized C6 cells, Ca++ at the concentration of 100 microM evoked PI hydrolysis, and ATP alone did not affect the Ca++ dependence. GTP gamma S (100 microM) stimulated the PI hydrolysis at a range of 0.1 to 10 microM Ca++, and ATP enhanced the GTP gamma S response in the permeabilized cells. These results suggest that activation of P2-purinergic receptors by ATP causes phospholipase C to be activated by subthreshold concentrations of Ca++ via GTP-binding proteins, resulting in an activation of the enzyme in response to stimulated Ca++ influx.

Adenosine Triphosphate↗

[The efficacy of transcatheter arterial infusion chemotherapy in patients with hepatocellular carcinoma].

The efficacy of transcatheter arterial infusion chemotherapy was examined for patients with hepatocellular carcinoma (HCC) between April 1986 and May 1992. We investigated the serial serum AFP level in patients with HCC. In 9 of 18 patients, the AFP level decreased promptly to 70% of the pretreatment level after this treatment. In 29 HCC patients with intrahepatic metastasis or portal thrombosis, 10 cases survived more than one year. However, only 3 cases survived more than two years after treatment. Our results suggest that we should carefully select appropriate drugs sensitive to HCC and also give careful consideration to the resistance to anti-cancer drugs.

Administration, Oral↗

Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats.

Antigen pretreatment through the oral or intraportal route has been reported to suppress antibody formation or delayed-type hypersensitivity (DTH) response to the same antigens. However, this effect on allografted organs has not been well studied. In this study we evaluated the efficacy for suppression of antibody formation and DTH response to the allogeneic antigens and tried to prolong liver allograft survival in rats. Male ACI (RT1a) rats were used as donors and male BUF (RT1b) rats as recipients. Intraportal or intravenous injection of spleen cells (SPCs) (5 x 10(7)) was performed through the mesenteric vein or the tail vein, respectively. The anti-ACI DTH response was tested by ear challenge of ACI SPCs. Cytotoxic antibody was assessed by complement-dependent cytotoxicity assay. ACI rat liver was transplanted orthotopically to BUF rat by the cuff technique 10 days after SPC injection. Cytotoxic antibody titer rose to X2(6) to X2(8) at 7 to 10 days after intravenous injection of SPCs. However, intraportal injection of the cells rarely caused a rise in antibody titer and even strongly suppressed subsequent antibody formation induced by intravenous injection when given 10 days before. The DTH response was also suppressed by intraportal injection of SPCs, with a mean value of 0.18 +/- 0.13 mm versus 0.67 +/- 0.19 mm for controls or 0.46 +/- 0.04 mm with intravenous injection. Liver-allografted rats died between 9 and 11 days, averaging 10.1 +/- 0.7 days in the control group. All seven transplants injected intraportally with donor SPCs survived more than 100 days, whereas six of eight rats injected intravenously with donor SPCs died of bleeding from the surface of the liver grafts within 12 hours after grafting, with signs similar to those of hyperacute rejection. Four of five rats injected intraportally with F344 (third-party) SPCs died of acute rejection in the same way the control rats died. The liver allograft-bearing rats had permanently accepted ACI skin grafts when tested 60 days after liver transplantation but rejected F344 skin grafts in the normal fashion. Intraportal injection of donor SPCs markedly suppressed the antibody formation, as well as the DTH response, and completely blocked liver allograft rejection. Moreover, the liver allograft-bearing rats proved to be fully tolerant of the donor antigen. This method might be a promising modality for inducing donor-specific tolerance in liver transplantation.

Animals↗

Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery.

Postoperative serum interleukin-6 (SIL-6) and C-reactive protein (SCRP) levels were examined in 71 patients who underwent various types of abdominal surgery. Similar time-dependent changes in SIL-6 and SCRP levels were observed in 12 patients despite differences in surgical procedures and liver function among the patients. SIL-6 started to increase within 3 hours after the beginning of the operation and reached a peak after 24 hours. SCRP started to increase after 12 hours and was maximum at 48 to 72 hours. The increase in SIL-6 at 24 hours (delta IL-6) showed a close correlation with that of SCRP at 48 hours (delta CRP) in 53 patients without liver cirrhosis. In 18 patients with liver cirrhosis, delta CRP relative to delta IL-6 was less than that in patients without cirrhosis and was poorly correlated with the latter. delta IL-6 was correlated with the length of time of the operation and blood loss in both groups, but delta CRP showed no significant correlation with these factors in either group. These findings indicate that the increase in IL-6 triggered by a surgical procedure may function as a hepatocyte-stimulating factor and that monitoring of SIL-6 may be more helpful than monitoring of SCRP for estimation of inflammatory status and early detection of an acute-phase response.

Abdomen↗

Effects of intracerebroventricularly administered neostigmine on sympathetic neural activities of peripheral tissues in rats.

Sympathetic nervous activity (SNA) in the liver, heart, pancreas and interscapular brown adipose tissue was examined 60 min after the third cerebroventricular injection of neostigmine (5 x 10(-8) mol) in rats. We employed the technique of specific gas chromatography-mass spectrometry for simultaneous analysis of norepinephrine (NE) and its primary neuronal metabolite, 3,4-dihydroxyphenylethyleneglycol (DHPG) and used the ratio DHPG/NE as an index of SNA. Neostigmine produced significant increases in the DHPG/NE ratio in all tissues investigated. Co-administration of atropine with neostigmine completely inhibited this neostigmine-induced effect. These findings suggest that the central cholinergic-muscarinic activation with neostigmine stimulates SNA in the peripheral tissues examined.

Adipose Tissue, Brown↗