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Biomedical subjects

M Inagaki

Publications and source records attributed to M Inagaki.

At least 19 recordsLinked to original sources
PubMed1995

The effects of nutritional repletion on donors for liver transplantation in pigs.

It has been shown that the nutritional state of the donor may affect the outcome of liver transplantation. However, many donors staying in the intensive care unit for a long period are in a reduced nutritional state. In this study, we investigated the effects of various methods of nutritional repletion on the outcome of liver transplantation in pigs. Donor pigs were divided into three groups according to the nutritional pretreatment given for 7 days before harvesting: group I were fasted and received intravenous administration of saline; group II were fed orally; group III were fasted, but given 20% glucose intravenously. Donor livers were stored for 4 hr in cold Euro-Collins' solution and transplanted. The serum AST level 24 hr after reperfusion remained at a lower level in group III compared with those in groups I and II. Bile production of the liver after transplantation was also well recovered in group III. The glycogen content of the liver at harvesting, which was completely consumed in group 1, was well preserved in groups II and III. These storages in both groups were rapidly consumed 1 hr after reperfusion. On the other hand, ATP content of the liver in groups I, II, and III, which were at a similar level at harvesting, were markedly decreased 4 hr after cold preservation and, 1 hr after reperfusion, recovered to 26%, 48%, and 73% of that before preservation, respectively. The mean survival time in group III was 37.2 days, significantly longer than 5.8 +/- 0.7 and 9.8 +/- 2.0 days in groups I and II, respectively (P < 0.01). These results show that the favorable outcome of liver transplantation depends on the glycogen storage in the donor liver, and also on ATP generation after reperfusion. Furthermore, it was suggested that ATP generation was affected by some unknown factor related to the method of nutritional repletion.

Adenosine Triphosphate↗
PubMed1995

Effects of various dopamine uptake inhibitors on striatal extracellular dopamine levels and behaviours in rats.

In vivo central effects of some dopamine uptake inhibitors were evaluated in both brain microdialysis and behavioural studies in rats, and compared with their in vitro affinities to dopamine uptake sites. IC50 values of GBR12909 (1-[2- bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine), diclofensine, mazindol, amfonelic acid and nomifensine for inhibiting 1 nM [3H]GBR12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) binding to rat striatal membrane were 7.0, 36, 81, 187 and 290 nM, respectively. In the brain microdialysis study, dopamine levels in the striatal dialysates were increased to 16.3- (GBR12909), 14.1- (nomifensine), 4.8- (diclofensine) and 1.9-fold (amfonelic acid) the respective basal levels 40-60 min after i.p. administration (0.1 mmol/kg) and thereafter decreased slowly but remained at the elevated levels for a further 3 h, while mazindol gradually increased dopamine levels though less pronouncedly than others (1.7-fold 200 min after administration). Remarkable and comparable stereotyped behaviours (licking and forepaw treading) were continuously observed at least for 3 h after administration of GBR12909, nomifensine and amfonelic acid, while stereotypies induced by diclofensine and mazindol were moderate and marginal, respectively. In vivo potencies of dopamine uptake inhibitors to increase the extracellular dopamine levels in the striatum tended to correlate with their in vitro affinities to dopamine uptake sites except in the case of nomifensine, and correlated significantly with their potencies to induce stereotyped behaviours except in the case of amfonelic acid. Based on these findings, pharmacological characteristics of these dopamine uptake inhibitors are discussed.

Animals↗
PubMed1995

Characterization of a human hepatoma cell line with acquired resistance to growth inhibition by transforming growth factor beta 1 (TGF-beta 1).

A new cell line (Hep 3B-TR), which is resistant to growth-inhibition by transforming growth factor beta 1 (TGF-beta 1) up to 10 ng/ml (400 pM), was isolated from parental Hep 3B human hepatoma cells, which are sensitive to growth-inhibition by TGF-beta 1. In the presence of TGF-beta 1 (1 to 10 ng/ml), the growth of the parental cell line (Hep 3B-TS) was inhibited by more than 95%. Under the same conditions, the growth rate of the resistant clone (Hep 3B-TR) however, was identical in the presence or absence of TGF-beta 1 and was almost the same as that of the Hep 3B-TS cells in the absence of TGF-beta 1. Affinity crosslinking with 5 pM 125I-labeled TGF-beta 1 showed that the TGF-beta 1 receptors type I (TGF-beta RI) and type II (TGF-beta RII) were not present on the cell surface of the Hep 3B-TR cells, whereas they were present on the sensitive HEP 3B-TS cells. Hep 3B-TS cells had detectable TGF-beta RII mRNA, which was not found in Hep 3B-TR cells. RNA analysis showed different effects on the expression of TGF-beta 1, c-fos, c-myc, and protein disulfide isomerase (PDI) genes in the two cell lines in response to TGF-beta 1 protein. Addition of TGF-beta 1 (1 ng/ml) strongly increased the expression of TGF-beta 1 mRNA in Hep 3B-TS cells, but not in Hep 3B-TR cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Hepatocellular↗
PubMed1995

Hepatectomy under extracorporeal circulation.

BACKGROUND: Resection of hepatic tumors located near the confluence of the hepatic vein or invading the inferior vena cava has become technically feasible and relatively safe by using venovenous bypass. However, some technical problems remain to be solved. METHODS: We performed three cases of hepatic resection under extracorporeal circulation combined with hypothermic perfusion. RESULTS: An unexpected hemorrhage was observed in all three cases for different causes. The patient of case 2 died of liver failure developed from fatty liver. Bile duct stenosis was observed in cases 1 and 3. CONCLUSIONS: Although hepatectomy under total vascular exclusion by use of Biopump is now considered a safe procedure, attention should be paid when this procedure is performed because some technical problems still remain.

Blood Loss, Surgical↗
PubMed1995

Degradation of c-Fos by the 26S proteasome is accelerated by c-Jun and multiple protein kinases.

c-Fos is associated with c-Jun to increase the transcription of a number of target genes and is a nuclear proto-oncoprotein with a very short half-life. This instability of c-Fos may be important in regulation of the normal cell cycle. Here we report a mechanism for degradation of c-Fos. Coexpression of c-Fos and c-Jun in HeLa cells caused marked increase in the instability of c-Fos, whereas v-Fos, the retroviral counterpart of c-Fos, was stable irrespective of the coexpression of c-Jun. Interestingly, deletion of the C-terminal PEST region of c-Fos, which is altered in v-Fos by a frameshift mutation, greatly enhanced its stability, with loss of the effect of c-Jun on its stability. c-Fos synthesized in vitro was degraded by the 26S proteasome in a ubiquitin-dependent fashion. Simple association with c-Jun had no effect on the degradation of c-Fos, but the additions of three protein kinases, mitogen-activated protein kinase, casein kinase II, and CDC2 kinase, resulted in marked acceleration of its degradation by the proteasome-ubiquitin system, though only in the presence of c-Jun. In contrast, v-Fos and c-Fos with a truncated PEST motif were not degraded, suggesting that they escaped from down-regulation by breakdown. These findings indicate a new oncogenic pathway induced by acquisition of intracellular stability of a cell cycle modulatory factor.

Amino Acid Sequence↗
PubMed1995

[A specific disorder of Kanji writing observed in a learning-disabled child--cognitive-psychological and neuropsychological analysis].

We reported a learning-disabled child who demonstrated a specific disorder of Kanji writing. A right-handed 13-year-old boy had showed no abnormality in general intelligence (VIQ114 and PIQ 100 in WISC-R), but could write only 35% of Kanji, which he should have learned six years before. It was necessary to develop a new test battery to detect the symptom which had not been detected using current existing test batteries. In cognitive-psychology, this patient had a retrieval disorder of graphic forms of Kanji. In addition, he showed a disorder in reproduction of complex graphic forms which he was asked to remember. Therefore, it is likely that he had a disorder for both Kanji and complex graphic forms, which is similar to the syndrome of pure agraphia of Kanji in adults.

Adolescent↗
PubMed1995

Pharmacokinetic study of trimethadione and its metabolite in blood, liver and brain by microdialysis in conscious, unrestrained rats.

A microdialysis method has been developed in the past two decades to determine levels of drug and endogenous compounds in several organs under physiological conditions. In this study, we determined the pharmacokinetics of the model drug, trimethadione (TMO), and its only metabolite, dimethadione (DMO), in liver, blood and brain by the microdialysis method in freely-moving rats. Sampling times were extended up to 24 hours. The construction of a newly developed microdialysis probe for liver and blood is described. The elimination patterns of TMO in liver, blood and brain dialyzates were almost identical and the calculated t1/2 was approximately 3 hr in each sample. However, in brain, tmax was delayed compared with the others while the relative concentration of DMO (AUC0-24h) was lower in brain compared with liver and blood. These studies suggest that this concurrent and successive microdialysis sampling method will not only be a useful tool for pharmacokinetic and drug metabolism studies in the organs of small animals but will also decrease the number of experimental animals needed for a study.

Animals↗
PubMed1995

[Increase in extracellular levels of serotonin and amino acids in the rat brain following cyanide-induced energy failure].

We studied the effects of ATP depletion on neurotransmitter release in the rat brain using the microdialysis method. Ringer's solution containing 2 mM sodium cyanide (NaCN) was perfused into the hippocampus and striatum for 60 min via a microdialysis probe, and changes in serotonin (5-HT) and amino acids (glutamate, aspartate and taurine) levels in dialysates were investigated. NaCN perfusion induced a transient 3.9-fold increase in 5-HT levels in the hippocampal dialysate. Amino acid levels in dialysates also increased during NaCN perfusion, but differently in the striatum and hippocampus (glutamate: 1.3- and 2.4-fold, taurine: 2.3- and 1.3-fold, respectively). Perfusion of Ca(2+)-free Ringer's solution remarkably suppressed the NaCN-induced increase in 5-HT but not the increases in amino acid levels. Depolarization by 100 mM KCl perfusion could induce increases in 5-HT and amino acids in dialysates at 3 hr after NaCN perfusion similarly with that of control. These findings indicate that the sensitivity of nerve terminals to energy failure are different between neurons containing different neurotransmitters and also between brain regions, and suggest that this regionally different sensitivity of amino acid neurons might be involved in the underlying mechanism of the localized vulnerability to transient ischemia.

Adenosine Triphosphate↗
PubMed1995

Extracorporeal circulation and hypothermic perfusion for caval tumor thrombus complicating hepatocellular carcinoma: a case report.

A tumor thrombus complicating hepatocellular carcinoma developed in a 61-year-old male patient. Embolization of the right branch of portal vein was performed 2 weeks before operation. Curative resection of the tumor was performed on by extended hepatectomy plus in situ hypothermic perfusion of the liver and extracorporeal circulation. Postoperative course was uneventful until bile leakage occurred on the 11th postoperative day. A bile duct stenosis was diagnosed by cholangiogram, and hepaticojejunostomy was carried out. The patient recovered well without further complications. The pitfalls and technical problems encountered in this case are herein discussed.

Carcinoma, Hepatocellular↗
PubMed1995

[Usefulness of adjuvant chemotherapy with antimetabolites for cervical invasive cancer].

A series of 584 patients with cervical invasive cancer were included in the retrospective study on the efficacy of long-term oral maintenance chemotherapy with antimetabolites (Fluorouracil or Tegaful). The patients were histologically classified into the squamous cell carcinoma (SCC) group and the adenocarcinoma (AD) group. In the SCC group (n = 518), 163 patients were given more than 300 mg/day of antimetabolite tablets for one year or more after the main therapy (hysterectomy or pelvic irradiation). In the AD group (n = 66), 36 patients were treated with the same dose of antimetabolites. The Kaplan-Meier overall and cancer specific survival analysis estimates that the chronic administration of antimetabolites did not improve the cumulative 5-year survival in the SCC group. In contrast, the cumulative 5-year survival rate in the AD group treated with antimetabolites (88%) was significantly higher than that without chemotherapy (64%) by Kaplan-Meier analysis. This significant improvement in the survival rate in the AD group due to antimetabolites was notable in patients in FIGO stage I or II treated with radical or semiradical hysterectomy, these results indicate that oral adjuvant chemotherapy with antimetabolites is useful for cervical adenocarcinoma, but not for squamous cell carcinoma.

Adenocarcinoma↗
PubMed1995

[Criteria of limited operation for bronchial carcinoid].

The purpose of this study is to establish criteria of limited operation for bronchial carcinoid. Ten cases surgically treated in our hospital and 47 cases reported in Japan from 1981 to 1992 were examined. Thirty-nine cases had typical carcinoid tumor and 18 had atypical. Limited operation, such as pulmonary segmentectomy, wedge resection or partial resection, was performed in 12 cases. In these, all patients of typical type were alive except for a case died of other disease. However, two patients of atypical type died of distant metastasis of the tumor. No lymph node metastasis was revealed in all cases of typical type. On the contrary, in cases of atypical type, six had n1 and two had n2 disease. Moreover, two cases with n1 disease had pulmonary metastasis. Therefore, patients with typical bronchial carcinoid can be cured by limited operation, but radical operation should be indicated for atypical bronchial carcinoid.

Adult↗
PubMed1994

Cervical magnetic stimulation in children and adolescents: normal values and evaluation of the proximal lesion of the peripheral motor nerve in cases with polyradiculoneuropathy.

Cervical magnetic stimulation was used to establish the normal values of the peripheral motor nerve conduction of the upper extremity muscle in normal children and adolescents. Seven patients with peripheral neuropathy were also examined to evaluate a lesion in the proximal site of the peripheral motor nerve. In normal subjects, onset latencies and negative wave durations tended to increase with age. The developmental profile of the latency, corrected for arm length, revealed a significant decline until the age of about 5 years. In 4 cases with polyradiculoneuropathy, motor evoked potentials following cervical magnetic stimulation showed increased latencies, prolonged durations and polyphasic shapes. The time differences between latencies by magnetic stimulation and peripheral motor conduction times by F technique were significantly prolonged. Motor evoked potentials obtained in 3 cases of axonal degeneration, on the other hand, showed slightly increased latencies and normal durations. The time differences between latencies and peripheral motor conduction times were within the normal range. Thus, we consider that cervical magnetic stimulation is a useful method for study of peripheral motor conduction in children and adolescents, and in particular to evaluate the proximal lesion of the nerve in patients with polyradiculoneuropathy.

Adolescent↗
PubMed1994

Spatiotemporal distribution of protein kinase and phosphatase activities.

Reversible protein phosphorylation plays an essential role in controlling cellular functions. Accumulating evidence indicates that the subcellular distribution of protein kinase and phosphatase activities is organized dynamically. The spatiotemporal dynamics of kinase and phosphatase activities appears to account for the elaborate coordination of the cellular functions achieved by protein phosphorylation and dephosphorylation.

Cell Cycle↗
PubMed1994

Identification of phosphorylation sites on glial fibrillary acidic protein for cdc2 kinase and Ca(2+)-calmodulin-dependent protein kinase II.

We identified the phosphorylation sites of glial fibrillary acidic protein (GFAP) for cdc2 kinase and Ca(2+)-calmodulin (CaM)-dependent protein kinase II. GFAP was phosphorylated to approximately 0.2 mol of phosphate/mol of GFAP by cdc2 kinase, and this phosphorylation did not induce disassembly of the filament structure. On the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did induce disassembly of the filament. Sequential analysis of the purified phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2 kinase, whereas Ser13, Ser17, Ser34, and Ser389 on GFAP were phosphorylated by Ca(2+)-CaM-dependent protein kinase II.

Amino Acid Sequence↗
PubMed1994

Transforming growth factor beta 1 selectively increases gene expression of the serine/threonine kinase receptor 1 (SKR1) in human hepatoma cell lines.

Human hepatoma cell lines (Hep 3B-TS, PLC/PRF/5, and Hep G2), sensitive to growth inhibition by transforming growth factor beta 1 (TGF-beta 1), express TGF-beta receptors type I, type II, and type III. We report that TGF-beta 1 protein selectively increased steady-state levels of the mRNA for the serine/threonine kinase receptor 1 (SKR1), a member of the TGF-beta superfamily receptor genes in these cells, whereas TGF-beta 1 had little effect on expression of the TGF-beta receptor type II gene. This increase of SKR1 mRNA in Hep 3B-TS cells could be detected by Northern blot analysis within 3 h of addition of TGF-beta 1 to the cells, and enhanced message levels peaked at 12 h as long as TGF-beta 1 was present in the culture medium. Hep 3B-TR cells which were resistant to TGF-beta 1 due to lack of both TGF-beta receptors type I and type II, expressed SKR1 mRNA, but it was not induced by TGF-beta 1 protein. The increased expression of SKR1 mRNA in the cells was actinomycin D-sensitive and was not dependent on new protein synthesis. The results indicate that TGF-beta 1 selectively induces SKR1 message at a transcriptional level by a positive regulator.

Blotting, Northern↗
PubMed1992

Effect of local cyanide perfusion on rat striatal extracellular dopamine and its metabolites as studied by in vivo brain microdialysis.

To investigate in vivo effects of energy failure on functions of dopaminergic neurons, we administered 0 (control), 0.2, 1 or 2 mM sodium cyanide (NaCN) dissolved in Ringer's solution for 60 min into the rat striatum through a brain microdialysis membrane. During NaCN perfusion, a transient and concentration-dependent increase in dopamine (DA) levels in the dialysate was observed. The maximum DA level during 2 mM NaCN perfusion was found to be 63-fold higher than the control levels. Leves of 3,4-dihydroxyphenylacetic acid and homovanillic acid were continuously lowered during and after NaCN perfusion. These data suggest that suppression of ATP production by NaCN induces an abrupt and remarkable increase in dopamine release from the nerve terminal in the striatum.

3,4-Dihydroxyphenylacetic Acid↗