Biomedical subjects

M Ishikawa

Publications and source records attributed to M Ishikawa.

At least 307 records · Page 17Linked to original sources

PubMed1997

Local muscimol disinhibits mesolimbic dopaminergic activity as examined by brain microdialysis and Fos immunohistochemistry.

Infusion of muscimol (5 X 10[-5] M, 60 min) into the nucleus accumbens (NAC) through a dialysis membrane caused a significant increase in extracellular dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). Fos-like immunoreactivity induced by intra-NAC infusion of muscimol was seen ipsilaterally in many accumbofugal target areas, but no Fos-positive neurons were seen in the vicinity of the dialysis membrane in the NAC. Sequential staining of Fos and tyrosine hydroxylase (TH) immunoreactivities revealed that a portion of A10 dopaminergic neurons were double-labelled. These results suggest that muscimol in the NAC disinhibits mesolimbic DA neuronal activity possibly through activity of the accumbofugal GABA neuron system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Prognostic significance of a clearly audible fourth heart sound detected a month after an acute myocardial infarction.

Patients (n = 181) with a myocardial infarction, with (n = 20) or without (n = 161) a clearly audible fourth heart sound detected 1 month after the onset of a myocardial infarction, were followed for 56.2 +/- 21.4 months for cardiac events (death, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery, worsening angina, or heart failure). The present study suggests that a clearly audible fourth heart sound detected 1 month after the onset of myocardial infarction increases the risk of adverse cardiac events.

Aged↗

PubMed1997

Analysis of the Rb gene and cyclin-dependent kinase 4 inhibitor genes (p16INK4 and p15INK4B) in human ovarian carcinoma cell lines.

In the present study, we analyzed human ovarian carcinoma cell lines for abnormalities in the tumor suppressor gene Rb (retinoblastoma) and in cyclin-dependent kinase 4 (CDK4) inhibitor genes (p16INK4 and p15INK4B) using molecular biology techniques. For the Rb gene, in all six cell lines (PA-1, Caov-3 and -4, OVCAR-3, SK-OV-3, and Kuramochi), Rb gene abnormality was not detected using Southern blotting. In the Caov-3 cell line transcripts were not detectable by either Northern blot or polymerase chain reaction. Sequence analysis of the entire coding region of the Rb gene revealed point mutations (AAC to GAC) resulting in codon 123 (Asn to Asp) changes in the Caov-4 cell line. In the PA-1 cell line both wild-type Rb and mutant-type Rb (codon 798: CGG to TGG) were expressed, and in the OVCAR-3 cell line both wild-type Rb and mutant-type Rb (codon 704: ATG to GTG) were expressed. In four of six human ovarian carcinoma cell lines Rb gene abnormality was detected. For the p16INK4 and p15INK4B genes, only the SK-OV-3 cell line had abnormalities. There was a gene rearrangement or minor deletion of the p16INK4 gene in the SK-OV-3 cell line, while the p15INK4B gene was deleted in this cell line. In the SK-OV-3 cell line no mRNAs of p16INK4 and p15INK4B were expressed. At the point of Rb gene inactivation, we can explain five cell lines of six: four cell lines had abnormalities in the Rb gene itself, which is another mechanism by which the Rb gene is inactivated, while one cell line (SK-OV-3) had abnormalities in CDK4 inhibitor genes, another of the inactivation mechanisms of the Rb gene. These data suggest that abnormalities of Rb and CDK4 inhibitor genes (p16INK4, p15INK4B) may be involved in human ovarian carcinogenesis.

Carcinoma↗

PubMed1997

A new method for estimating spinal cord function. Refractory period of conductive spinal cord evoked potentials.

STUDY DESIGN: This study was designed to examine the possibility of a new spinal cord monitoring method using measurement of the refractory period to monitor spinal cord function. OBJECTIVES: To determine whether measuring the refractory period and the recovery rate of conductive spinal cord evoked potential is a useful method for estimating spinal cord function. BACKGROUND: Measuring the refractory period and constructing the recovery curve have been used to investigate peripheral nerve function. Spinal cord evoked potential elicited by the single stimulus usually is used to evaluate spinal cord function, and it has been said that 50% attenuation of the amplitude is the critical alarm level. METHODS: In anesthetized cats, amplitude, area, and latency were measured on a personal computer from subtracted data collected with a paired-stimulation technique. The authors constructed recovery curves of ascending and descending conductive spinal cord evoked potentials and measured the refractory period during spinal cord compression. RESULTS: When the amplitude of the ascending spinal cord evoked potential began to decrease during spinal cord compression, the amplitude of the response elicited by the second stimulus with interstimulus intervals of 0.8 msec and 1.0 msec decreased more significantly. When the amplitude of the ascending spinal cord evoked potential decreased to 50% of the precompression amplitude, the mean value of the absolute refractory periods of the ascending and descending spinal cord evoked potentials became prolonged from 0.40 +/- 0.007 msec to 0.53 +/- 0.014 msec, and the mean values of their amplitude and area recovery rates decreased from 75% +/- 1% to 35% +/- 2% (interstimulus interval, 0.8 msec) and from 81% +/- 1% to 46% +/- 2% (insterstimulus interval, 1.0 msec). CONCLUSIONS: The change of the responses elicited by the paired stimuli is more sensitive than those elicited by the single stimulus in the spinal cord evoked potentials. The absolute refractory periods and the recovery rate during 50% attenuation of the precompression amplitude is the critical alarm level in spinal cord monitoring.

Animals↗

PubMed1997

Acetaminophen absorption test as a marker of small bowel transplant rejection.

We recently evaluated the acetaminophen absorption test as a marker of graft rejection for small bowel transplantation(SBTX). Randomly bred male Wistar rats were used as recipients and donors. Rats (n=45) received heterotopic small intestinal transplants and were divided into three groups (n=15 for each group). In group A, a 10-cm segment of jejunum of was exteriorized as a Thiry-Vella loop. In group B, immunosuppression was not given after SBTX. In group C, rats were treated with FK506 after SBTX (0.3 mg/kg body weight, 0-6 postoperative days). Serum acetaminophen concentrations were measured 15 min after instillation of 0.15 g/kg acetaminophen into the intestinal loop on postoperative days 1, 3, and 7 (n=5 for each group). Blood flow and histology of the graft were also evaluated. In the SBTX group only, the grafts showed the histological change after acute rejection. On day 3, plasma acetaminophen concentrations in this group showed a significant decrease, which correlated with the mild histological changes of graft rejection. Graft blood flow of the SBTX group decreased significantly on day 7, following the severe graft destruction of advanced rejection. No remarkable changes were observed in the other two groups. The acetaminophen absorption test appears to be useful for the early detection of SBTX graft rejection.

Absorption↗

PubMed1997

Somatostatin release as measured by in vivo microdialysis: circadian variation and effect of prolonged food deprivation.

In vivo microdialysis was used to determine SRIF release from the hypothalamus in unanesthetized male rats over a period of 24 h and in rats deprived of food for 72 h, in relation to changes in plasma GH levels. Before the experiment, a microdialysis probe was inserted into the anterior pituitary gland of the rats with an indwelling right atrial cannula. Dialysates and blood samples were collected serially, after normal feeding or 72-h deprivation of food. Normal rats implanted with the microdialysis probe showed an episodical pattern of GH secretion at intervals of 3 h. SRIF was secreted in a pulsatile fashion in the dark period in a similar manner to the light period. Mean SRIF pulse amplitude and mean SRIF level were significantly increased in the dark period. There was no significant correlation between the SRIF and GH pulses in the light period. SRIF levels in dialysates obtained from fed rats and food-deprived rats showed a pulsatile pattern. Food deprivation resulted in significant increases in mean SRIF level and mean SRIF pulse amplitude. These results suggest that the existence of circadian rhythm in SRIF release and the increase in SRIF release play an important role in suppressing GH secretion during prolonged food deprivation.

Animals↗

PubMed1997

Central vasopressin is required for the complete development of deoxycorticosterone-salt hypertension in rats with hereditary diabetes insipidus.

It has been shown that vasopressin receptors are upregulated in the brain and that the central vasopressin pathway is involved in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. However, it is unclear whether central vasopressin, in itself, is essential for this type of hypertension. To clarify this issue, the effect of centrally administered vasopressin on the development of DOCA-salt hypertension was studied in homozygous Brattleboro rats which genetically lack vasopressin. In homozygous Brattleboro rats, treatment with intracerebroventricular infusion of vasopressin (1 ng/h) alone or DOCA-salt (weekly subcutaneous injection of 30 mg/kg deoxycorticosterone acetate and 0.3% NaCl to drink) alone had no effect on systolic blood pressure (SBP). On the other hand, hypertension was partially restored in homozygous Brattleboro rats treated with intracerebroventricular infusion of vasopressin and DOCA-salt (SBP: 175 +/- 4 mmHg), although the magnitude of elevation of SBP was one-third of that in Long Evans rats treated with DOCA-salt (278 +/- 15 mmHg). These hypertensive homozygous Brattleboro rats showed an increase in fluid intake and urinary sodium excretion, as observed in DOCA-salt hypertensive Long Evans rats. These results suggest that central vasopressin is required for the complete development of DOCA-salt hypertension and the mechanism is, in part, due to enhanced sodium intake through the additive effect of central vasopressin and DOCA-salt.

Animals↗

PubMed1997

Nonlinearity identified by neural network models in Pco2 control system in humans.

The nonlinearity included in the PCO2 control system in humans is evaluated using the degree of nonlinearity based on a difference of residuals. An autoregressive moving average (ARMA) model and neural networks (linear and nonlinear) are employed to model the system, and three types of network (Jordan, Elman and fully interconnected) are compared. As the Jordan-type linear network cannot approximate respiratory data accurately, the other two types and the ARMA model are used for the evaluation of the nonlinearity. The results of the evaluation indicate that the linear assumption for the PCO2 control system is invalid for three subjects out of seven. In particular, strong nonlinearity was observed for two subjects.

Adult↗

PubMed1997

Polymorphic and tissue-specific imprinting of the human Wilms tumor gene, WT1.

We previously demonstrated maternal monoallelic expression of the Wilms tumor suppressor gene, WT1, in about half of pre-term placental villus and fetal brain tissues examined. There were two alternative explanations for this pattern of the WT1 expression, i.e., an imprinting polymorphism vs. a developmental stage-dependent switching from monoallelic to biallelic expression of the gene. To investigate these possibilities, we examined WT1 expression in a larger number of villus samples (46 samples) with gestational ages ranging from 4 to 21 weeks, using reverse transcriptase-based polymerase chain reaction (RT-PCR) to amplify the sequences for polymorphic sites in the 3'-untranslated region (UTR) of WT1. Maternal monoallelic expression was observed in 7 (39%) of 18 samples informative for the polymorphism, while the expression of the remaining 11 samples was biallelic. In addition, there was no correlation between expression patterns and gestational ages of the samples. The results indicate that the pattern of expression (monoallelic vs. biallelic) is polymorphic. The expression patterns were also studied in five different organs from a 21-week-old fetus, showing monoallelic expression only in the placenta and biallelic expression in other organs (heart, lung, liver and intestine). The finding supports the tissue specificity of the WT1 monoallelic expression.

Alleles↗

PubMed1997

Effects of spinal cord ischemia on the refractory period of descending spinal cord evoked potential.

The recovery cycle, following the conduction of action potentials along a nerve fiber, consists of the absolute refractory period (ARP), the relative refractory period (RRP) and the supernormal period (SNP). The recovery cycle of the descending conductive spinal cord evoked potential (SCEP) was shown during normal state, ischemia and after ischemia using paired stimuli in cats. During ischemia the refractory period revealed a trend towards increment. Five minutes after reperfusion the refractory period decreased transiently compared with the normal level and within 30 min the refractory period returned to the normal level. The recovery curve of the 2nd potential showed different pattern compared with that of the 1st potential. Moreover, during ischemia, firstly the 3rd potential and secondly the 2nd potential of the SCEP elicited by the 2nd stimulus were disturbed. These results demonstrated that there is increased excitability of the spinal cord to the second stimulus after a brief period of ischemia, and that the 2nd and 3rd potentials are evoked synaptically and easily disturbed during ischemia. Measuring the SCEP elicited by paired stimuli or constructing the recovery curve of the SCEP is useful for the electrophysiological assessment of spinal cord function.

Action Potentials↗

PubMed1997

Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells.

The present study was performed to elucidate the mechanism underlying the anti-atherogenic action of estrogen. We investigated the effect of estrogen on intimal thickening of the rat femoral artery induced by cuff placement and further examined the effect of estrogen on migration and proliferation of vascular smooth muscle cells (VSMCs) in culture. Intimal thickening was significantly greater in males than in control females. Intimal thickening in females was increased to the level in males by ovariectomy. Estrogen replacement to ovariectomized rats reversed this effect. Proliferating cell nuclear antigen immunohistochemistry showed that in vivo proliferation of VSMCs contributed to the difference in intimal thickening. There was no difference in blood pressure and serum lipids, suggesting that estrogen directly acted on artery and inhibited intimal thickening. 17 beta-Estradiol (E2, 1-100 nmol/l) inhibited migration of cultured rat VSMCs, assayed using a microchemotaxis chamber, in a concentration-dependent manner. E2 (0.01-100 nmol/l), but not progesterone or testosterone, also inhibited [3H]thymidine incorporation in rat VSMCs in a concentration-dependent manner. Indomethacin, NG-monomethyl-L-arginine and methylene blue did not influence the inhibitory action of E2 on [3H]thymidine incorporation, suggesting that prostanoids and nitric oxide are not involved in the action of E2. E2 did not provoke VSMC injury, as measured by the release of incorporated [3H]2-deoxy-D-glucose. These results suggest that the inhibition of migration and proliferation of VSMCs contributes to the inhibitory effect of estrogen on intimal thickening.

Animals↗

PubMed1997

Comparative study of toborinone (OPC-18790) and milrinone on energy metabolism in microembolized guinea pig hearts.

The effects of toborinone (OPC-18790) and milrinone on cardiac function and energetics were compared in microembolized guinea pig hearts. Male guinea pig hearts were perfused according to the Langendorff method and microembolization was induced by injecting microspheres. The hearts were then treated with toborinone (10 microM), milrinone (4 microM), and vehicle. Energy metabolism in hearts was assessed by 31-phosphorus magnetic resonance spectroscopy (31P-MRS). Microembolization produced a decrease in coronary perfusion flow (CPF), left ventricular developed pressure (LVP), and peak LVdP/dt by about 50% concomitantly with a decrease in creatine phosphate (PCr) and ATP and an increase in inorganic phosphate (Pi) and Pi/PCr ratio. Toborinone and milrinone increased peak LVdP/dt, an index of contractility, by 15 +/- 2% and 18 +/- 3%, respectively. Milrinone increased heart rate (HR) by 22 +/- 4% but toborinone did not change HR. Toborinone did not change PCr, ATP, Pi, Pi/PCr, and intracellular pH (pHi) compared with the vehicle. On the other hand, milrinone decreased PCr and increased Pi and Pi/PCr compared with toborinone or vehicle. These results suggest that the different effects between toborinone and milrinone on energy metabolism in microembolized hearts may be due to the difference of chronotropic action between these drugs. Thus toborinone, a positive inotropic agent without chronotropic action, may be effective in acute treatment of ischemic heart failure.

Animals↗

PubMed1997

Preference of peanut agglutinin labeling for long-wavelength-sensitive cone photoreceptors in the dace retina.

Peanut agglutinin (PNA) was known for its selective binding to cone cells. In the present study, we investigated whether there was any difference in PNA binding among various subtypes of cone photoreceptor cells in the dace retina. The outer segments of the long-double- and long-single-cone cells were preferentially labeled with PNA. Ultrastructural pre-embedding labeling revealed that the binding sites of PNA were confined to the calycal processes of these cells. By contrast, only slight labeling was discerned on the corresponding regions of other types of cone cells. The results indicate that PNA can distinguish the long-wavelength-sensitive cone from the short-to-middle-wavelength-sensitive cone cells.

Animals↗

PubMed1997

Behavioral LTP during learning in rat hippocampal CA3.

Behavioral long-term potentiation (LTP) of the potentials with the advance of learning were investigated in hippocampal mossy fiber (MF)-CA3 synapses. In both acute and chronic experiments, control and test groups of rats were used. Daily learning tasks in the radial arm maze were given to animals in the test groups. Complete acquisition of learning was observed on day 5. In acute experiments, when MF stimulation-induced population spikes (PS) were examined on day 7 of learning task, relatively higher PS were observed in the test group than those in the control group, and tetanic stimulation (TS)-induced LTP was still observed from the increased PS before TS in the test groups. In chronic experiments, in which the MF stimulation-induced PS were recorded daily after the learning tasks with implanted electrodes, amplitude of PS of the test groups, but not the control, increased concomitantly with the progress in learning. The PS potentiation persisted steadily from day 4 to day 7 of training. The fact that LTP in the MF-CA3 system coincided well with the advance of learning suggests that the MF-CA3 system is involved in the acquisition of learning and/or memory storage.

Anesthesia↗

PubMed1997

Stimulation of angiotensin subtype 2 receptor reduces basal cGMP levels in the neointima of rat aorta after balloon injury.

1. The association between the stimulation of the angiotensin subtype 2 receptor (AT2-R) and the change in tissue levels of cyclic nucleotide was assessed on neointima formation in rat aorta following aortic balloon injury. 2. Tissue levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate levels (cAMP) in the injured and uninjured aorta was determined by enzyme immunoassay at baseline and again 30 s after administration of 10(-7) M angiotension II. 3. Injured and uninjured aorta showed no difference in basal levels of cGMP. Angiotension II reduced the basal level of cGMP in the injured aorta only. 4. This decrease was blocked by a selective AT2-R antagonist (PD123319) and by a nonselective angiotensin II antagonist (angiotensin II antipeptide), but not by a selective angiotensin subtype 1 antagonist (CV-11974). 5. Stimulation with a selective AT2-R caused no change in the level of cAMP in the injured or uninjured aorta. 6. Results suggest that stimulation of AT2-R in proliferative neointima leads to a decreased tissue level of cGMP.

Angiotensin II↗

PubMed1997

Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with decreased hydrophobicity.

In order to study structure-activity relationships of the previously reported dual histamine H2 and gastrin receptor antagonists and also to improve their low oral absorbability, we tried two chemical modifications. One tried to decrease the high hydrophobicity of the parent hybrid compounds to an appropriate level by incorporating a hydrophilic group into the molecule and the other by replacing the more hydrophobic groups with less hydrophobic ones. The former compounds (type I) involved hybrid compounds with a hydroxyl group at a position of a spacer, a piperidine moiety of H2A, or a phenyl ring at the C5 of the benzodiazepine skeleton as well as those with a free carboxyl group in the piperidine moiety of H2A. The latter (type II) involved hybrid compounds with the C5-phenyl group replaced with either a methyl group or hydrogen atom. Among them, only a type I compound, ([2-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl] ethylcarbamoyl]methyl)carbamic acid 3-[3-[5-(3-hydroxyphenyl)-1-methyl-2-oxo-2,3-dihydro-1H-1,4-benzodiaz epin-3-yl]ureido]benzyl ester (18), showed potent dual histamine H2 and gastrin receptor antagonistic activity, whereas others resulted in a significant decrease of histamine H2 receptor antagonistic activity. The in vivo gastric acid antisecretory activity of 18 evaluated by Schild's rat method, however, did not suggest any notable improvement in oral absorbability.

Animals↗

PubMed1997

Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with modified benzodiazepine skeletons.

Three different types of dual histamine H2 and gastrin receptor antagonists, e.g. those bearing a benzazepine, benzoxazepine, or benzothiazepine skeleton instead of the benzodiazepine one as a gastrin receptor antagonistic moiety were synthesized to reduce high hydrophobicity of parent compounds and evaluated for the dual activities. These skeletal modifications significantly potentiated the binding affinity of dual antagonists with histamine H2 receptor but markedly diminished their binding affinity with the gastrin receptor and the gastrin versus CCK-A receptor selectivity. We evaluated in vivo gastric acid antisecretory activities for some representative compounds by the rat pylorus ligation method for 10 mg kg(-1) dose by oral route. However, they exerted only low inhibitory activities for oral dose with % inhibition values ranging between 32 and 53%.

Animals↗

PubMed1997

Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with noncyclic gastrin receptor antagonistic moieties.

In order to study structure-activity relationships of dual histamine H2 and gastrin receptor antagonists as well as to improve their low oral absorbability, their prototype benzodiazepine gastrin receptor antagonistic moieties were altered to a conformationally flexible noncyclic dipeptide equivalent. This skeletal modification significantly potentiated the binding affinity of hybrid compounds for the histamine H2 receptor, whereas their affinity for the gastrin receptor and receptor selectivity over the CCK-A receptor varied widely with the substituents on the gastrin moiety. Among them, [3-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]p ropyl carbamic acid 3-[3-([(3-methoxyphenyl)[(methylphenylcarbamyl)methyl]carbamoyl]me thyl)ureido]benzyl ester (7a) showed the highest dual histamine H2 and gastrin receptor antagonistic activities. It also displayed distinct gastric acid antisecretory activity in vivo for two assays, namely, Schild's rat method by i.d. administration and the rat pylorus ligation method by oral administration. With the latter case, dose-response relationships were observed for the first time, suggesting its substantially improved oral absorbability. However, 7a did not display distinct in vivo gastric acid antisecretory activity for the assay with Heidenhain pouch dogs.

Absorption↗