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Biomedical subjects

M Inagaki

Publications and source records attributed to M Inagaki.

At least 199 records · Page 11Linked to original sources
PubMed1996

[Neonatal brain injury and evoked potentials].

Marked abnormalities in ABR at discharge from NICU can predict overall prognosis in patients with neonatal asphyxia. However, in patients with neonatal asphyxia as a single risk factor, the incidence of ABR abnormalities was low and ABR was not indicative of their long-term prognosis. Over the past 10 years, we encountered 13 patients with deterioration of ABR and progressive hearing impairment after discharge from NICU. All patients showed severe cardiorespiratory symptoms in the neonatal period. Nine of thirteen patients were diagnosed as persistent neonatal pulmonary hypertension. Multimodal evoked potential studies could predict life expectancy and functional state in patients with severe motor and intellectual impairment. These kind of neurophysiological test can show the patients' functional state at the time of the examination. Discrepancies in evoked potentials and clinical symptoms provide important information regarding the pathophysiology of the patients.

Asphyxia Neonatorum↗
PubMed1996

[Auditory perception in patients with multiple and severe handicaps: study of mismatch negativity to speech sounds].

We have found that the mismatch negativity (MMN) of event-related potentials (ERPs) to the tone burst sound is generated passively in some multiple and severe handicapped patients. This study investigated whether 10 patients with severe handicaps, whose auditory perception is hard to be evaluated clinically, exhibited MMN to the speech sound (SS). The stimuli included tone bursts of 700 and 1000 Hz in frequency, and 4 patterns of SS (1 phoneme: [a, ae], [a, o]; and 2 phonemes: [amo, ano], [ao, aka]) presented at an 85: 15 occurrence with 75 dBSPL. In the tone burst paradigm, 7 patients had a definite MMN wave followed by an N1 wave. However, a few patients showed MMN to some patterns of SS. The latency of MMN to SS was almost within normal limits. These results suggest that these patients could discriminate subtle differences of frequency in some speech sounds, although their auditory response to actual speech sounds were poor.

Adolescent↗
PubMed1996

An effective tool to detect lesions causing unstable angina with multivessel disease: iodine-123-betamethyl-p-iodophenyl-pentadecanoic acid single photon emission computed tomography.

Radiolabeled fatty acids such as iodine-123-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) have unique metabolic properties suggesting potential use as myocardial perfusion tracers. The uptakes of BMIPP and thallium 201 were compared using single photon emission computed tomography (SPECT) in 24 patients displaying unstable angina with multivessel disease at a mean of 3.4 days after admission. Coronary angiography was performed within a week. Uptake was considered normal if the activity was greater than 80% of the normal area, mildly reduced if 50% to 79%, and severely reduced if less than 50%. The regional activities in four quardrants in short-axis slices were measured from basal, mid and apical sets. We attempted to identify the causative lesion on dual SPECT imaging. We planned the following management of each patient based on the results of the dual SPECT study. BMIPP activity imaging found 4 segments (1.4%) with severe decrease, 70 (24.3%) with mild decrease, and 214 (74.3%) with normal uptake. In contrast, T1 activity imaging showed normal uptake in 68 of 74 abnormal BMIPP activity segments. Furthermore, all segments with abnormal BMIPP uptake were matched with locations of coronary artery stenosis by coronary angiography. Accordingly, coronary revascularization (percutaneous transluminal coronary angioplasty, coronary artery bypass grafting) was performed based on BMIPP SPECT. Reductions in BMIPP activity were common in patients with unstable angina with multivessel disease. BMIPP SPECT is an excellent tool for detecting the causative lesion in unstable angina. The subsequent intervention could be performed with less risk based on the strategy of dilating the only causative lesion which was detected by the BMIPP SPECT in patients with multivessel disease displaying unstable angina.

Angina, Unstable↗
PubMed1996

Safety and effectiveness of exercise training in patients with silent myocardial ischemia.

The effectiveness of exercise training in patients with silent myocardial ischemia was examined. Forty patients with coronary heart disease (mean age 55 +/- 8 years) were recruited for a 12-week exercise training program. All patients underwent treadmill exercise stress testing, exercise thallium-201 single photon emission computed tomography and left heart catheterization. They were divided into three groups based on the symptoms and the results of exercise thallium scintigraphy, i.e., painful myocardial ischemia (PMI group), silent myocardial ischemia (SMI group), and non-myocardial ischemia (NMI group). Normalized treadmill time was longer in the SMI group (108 +/- 24%) than in the PMI group (86 +/- 14%, p < 0.05). All 40 patients, 14 from the PMI group, 16 from the SMI group and 10 from the NMI group, completed the whole exercise training program. A significant prolongation of treadmill time was attained in all three groups after exercise training [PMI group: from 494 +/- 105 to 632 +/- 78 sec (p < 0.05), SMI group: from 609 +/- 147 to 746 +/- 137 sec (p < 0.05), NMI group: from 572 +/- 112 to 739 +/- 13 sec (p < 0.05)]. The improvement of myocardial ischemia following exercise training was similar in the SMI and PMI groups. No adverse effects were detected throughout the program. The exercise training program adopted in this study proved safe and effective in patients with silent myocardial ischemia.

Adult↗
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

Visualization and function of vimentin phosphorylation by cdc2 kinase during mitosis.

To investigate the role of intermediate filament (IF) protein phosphorylation by cdc2 kinase during mitosis, we developed a monoclonal antibody 4A4 recognizing Ser55-phosphorylated vimentin. Western blotting indicated that this antibody reacted with vimentin phosphorylated by cdc2 kinase but not with non-phosphorylated vimentin or with vimentin phosphorylated by other kinases such as cAMP-dependent protein kinase, protein kinase C, or Ca(2+)-calmodulin-dependent protein kinase II. Immunofluorescence and immunoelectron microscopy showed that vimentin Ser55 residues distributed in the entire cytoplasmic vimentin filament system are phosphorylated when the cells enter mitosis and dephosphorylated in cytokinesis. All cell lines examined showed a similar appearance of immunoreactivity with antibody 4A4. Fractionation of mitotic cell extracts on Mono-Q Sepharose revealed a single peak of vimentin Ser55 kinase activity, and the anti-p34cdc2 antibody reacted with the 34 kDa band in the kinase containing fractions. Vimentin Ser55 kinase activities were nil in the interphase cell extract. Immunofluorescent evidence using antibody 4A4 and biochemical analysis using vimentin Ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase.

Amino Acid Sequence↗