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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 847 records · Page 47Linked to original sources
PubMed1992

Impaired NK response of cancer patients to IFN-alpha but not to IL-2: correlation with serum immunosuppressive acidic protein (IAP) and role of suppressor macrophage.

In vitro NK responses of cancer patients (N = 21) to rIFN-alpha A and rIL-2 were examined. The serum concentration of IAP (immunosuppressive acidic protein) was determined in parallel. Five out of seven patients whose serum IAP contents were within the normal range (270 micrograms/ml to 470 micrograms/ml), had their NK activities significantly augmented by rIFN-alpha A and rIL-2. On the other hand, NK cells from ten out of fifteen patients whose serum IAP concentrations were 650 micrograms/ml or more, were not activated by rIFN-alpha A. NK cells of these fifteen patients yet were capable of responding to rIL-2. NK cells from cancer patients, however, became responsive to rIFN-alpha A by either removal of adherent cells or treatment with indomethacin. Therefore, macrophages in PBMC of cancer patients with high serum IAP levels seem to selectively suppress NK response to rIFN-alpha A by an indomethacin-sensitive mechanisms. It was further shown that PGE2 was not the mediator of this suppression.

Adult↗
PubMed1992

Complete cure of urinary and faecal incontinence after intravenous vitamin B12 therapy in a patient with post-gastrectomy megaloblastic anaemia.

The case of a 59-year-old Japanese woman with post-gastrectomy megaloblastic anaemia having urinary and faecal incontinence and paraesthesia in four extremities is described. While the haematological abnormalities were improved by administration of a total dose of 17 mg of intramuscular mecobalamin, the neurological abnormalities remained unchanged. Five months later, a total dose of 7.5 mg of mecobalamin was injected intravenously over a period of 5 weeks, although the serum level of vitamin B12 was greater than 1180 pmol l-1. Immediately after initiation of the therapy, the urinary and faecal incontinence were gradually improved, and were completely cured within 2 months. The peripheral neuropathy was also ameliorated. The effectiveness of intravenous vitamin B12 injection for the neurological abnormalities due to vitamin B12 deficiency is emphasized.

Anemia, Megaloblastic↗
PubMed1992

Presynaptic inhibitory effects of the peptides NPY, PYY and PP on nicotinic EPSPs in guinea-pig gastric myenteric neurones.

1. Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) affect gastrointestinal effector systems. Although their precise mode of action is unknown it is suggested that their effects are partly mediated by enteric neurones. Therefore, the aim of this study was to investigate the effects of NPY, PYY, avian PP (aPP) and bovine PP (bPP) on the electrophysiological behaviour of gastric myenteric neurones using intracellular recording methods. 2. In all thirty-one neurones tested, electrical stimulation of interganglionic fibre tracts evoked cholinergic, nicotinic fast excitatory postsynaptic potentials (fEPSPs). NPY, PYY and bPP (10-500 nM) inhibited the fEPSPs in a concentration-dependent manner. Additionally, these peptides reversibly abolished spontaneously occurring nicotinic fEPSPs. None of the peptides exhibited any effect on the response to exogenously applied acetylcholine or on the postsynaptic excitability of the neurones. The inhibitory effects on the fEPSPs could not be reversed by perfusion of the alpha-adrenoceptor antagonist, phentolamine (1 microM). 3. In contrast, aPP had no significant effect on fEPSPs even when perfused at the high concentration of 1 microM. 4. The results suggest that NPY, PYY and bPP, but not aPP, act presynaptically to inhibit acetylcholine release from myenteric neurones of the gastric corpus, thereby suppressing fEPSPs. The study indicates a modulatory role for NPY, PYY and bPP in synaptic interactions within the enteric nervous system.

Animals↗
PubMed1992

Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor.

Our recent studies with cell mutants indicate that a cascade shared by the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) signals exists in NRK cells and mediates oncogenic signals induced by many oncogenes (A. Masuda, S. Kizaka-Kondoh, H. Miwatani, Y. Terada, H. Nojima, and H. Okayama, New Biol. 4:489-503, 1992). We have employed the antisense RNA technique to investigate possible involvement of Raf-1 kinase in this signal transduction cascade. NRK cell clones highly reduced in the Raf-1 production are generated by the expression of a c-raf-1 antisense RNA. They have no apparent growth defects and retain proper mitotic responses to growth factors but are refractory to transformation by EGF or PDGF plus transforming growth factor beta, v-erbB, v-fms, v-K-ras, v-mos, v-fos, v-src, simian virus 40 large T, and polyomavirus middle T but not by v-raf or adenovirus E1A. These results not only support our model for the oncogenic signal cascade but also lead to the conclusion that Raf-1 protein kinase is a downstream component of this oncogenic signal cascade shared by EGF and PDGF.

Blotting, Western↗
PubMed1992

Morphology of electrophysiologically identified myenteric neurons in the guinea pig rectum.

Dye-filled microelectrodes were used to investigate relations between morphology and electrophysiological behavior of neurons in the myenteric plexus of the guinea pig rectum. The neurons were divided into two general classes on the basis of morphology. The first class had smooth ovoid somas with multiple long processes that exited the ganglion in several different fiber tracts and fit the description of Dogiel type II neurons. Neurons of the second class had a single long process that exited the ganglion in a fiber tract and sometimes projected to the circular muscle. Neurons of the second class were subdivided into three groups. One of these had short club-shaped dendrites like Dogiel type I neurons. Another had short tapering filamentous processes. Neurons with a single long neurite that could not be classified made up the third group. AH/type 2 electrophysiological behavior was found in both general classes of neurons. S/type 1 electrophysiological behavior occurred only in neurons of the general class with a single long neurite. Type 3 electrical behavior, characterized by robust fast synaptic input in inexcitable neurons, was found only in the cells defined by a single long neurite. Single-spike neurons behaved electrophysiologically like AH/type 2 neurons without long-lasting hyperpolarizing afterpotentials. This behavior was limited to the class of neurons characterized morphologically by a single long neurite.

Action Potentials↗
PubMed1992

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion.

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vivo recording of electrical activity of canine tracheal smooth muscle.

Electrical activity of the tracheal smooth muscle was studied using extracellular bipolar electrodes in 37 decerebrate, paralyzed, and mechanically ventilated dogs. A spontaneous oscillatory potential that consisted of a slow sinusoidal wave of 0.57 +/- 0.13 (SD) Hz mean frequency but lacked a fast spike component was recorded from 15 dogs. Lung collapse accomplished by bilateral pneumothoraxes evoked or augmented the slow potentials that were associated with an increase in tracheal muscle contraction in 26 dogs. This suggests that the inputs from the airway mechanoreceptors reflexly activate the tracheal smooth muscle cells. Bilateral vagal transection abolished both the spontaneous and the reflexly evoked slow waves and provided relaxation of the tracheal smooth muscle. Electrical stimulation of the distal nerve with a train pulse (0.5 ms, 1-30 Hz) evoked slow-wave oscillatory potentials accompanied by a contraction of the tracheal smooth muscle in all the experimental animals. Our observations in this in vivo study confirm that the electrical activity of tracheal smooth muscle consists of slow oscillatory potentials and that tracheal contraction is at least partly coupled to the slow-wave activity of the smooth muscle.

Action Potentials↗
PubMed1992

Effect of 15-deoxyspergualin on lupus nephropathy in New Zealand black/white F1 mice.

Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.

Animals↗
PubMed1992

Functional changes of the exocrine perfused rat pancreas in cerulein-induced pancreatitis.

Functional changes of the exocrine pancreas in cerulein-induced pancreatitis were evaluated with the isolated perfused rat pancreas. In control specimens (n = 7), baseline pancreatic juice volume was 0.23 +/- 0.06 microliter/min and after stimulation with CCK-8 (10(-10) M) and secretin (10(-10) M), it was 2.26 +/- 0.45 microliter/min, and in cerulein-induced pancreatitis specimens (n = 8), the corresponding values were 0.11 +/- 0.03 and 0.23 +/- 0.08 microliter/min. The amylase content in the pancreatic juice (IU/min) was 0.73 +/- 0.15 (baseline) and 7.03 +/- 1.66 (stimulated) in the control specimens, and 0.012 +/- 0.002 (baseline) 0.018 +/- 0.004 (stimulated), in the cerulein-induced pancreatitis specimens. Amylase and lipase concentrations in the portal effluents were significantly higher in the cerulein-induced pancreatitis (481.3 +/- 79.4 IU/ml, 283.7 +/- 47.2 BALB U/ml) than in the control specimens (10.7 +/- 1.8 IU/ml, 8.9 +/- 2.9 BALB U/ml). Using the electron microscope fusion of large vacuoles with lateral plasma membrane was observed in cerulein-induced pancreatitis. In cerulein-induced pancreatitis, normal secretion was markedly decreased, and the lateral secretion was suggested to result in the elevation of pancreatic enzyme levels in portal effluents.

Amylases↗
PubMed1992

Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin.

BACKGROUND AND PURPOSE: The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin. METHODS: We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine. RESULTS: Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin. CONCLUSIONS: These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

The effect of pretreatment with moricizine on early arrhythmia resulting from myocardial ischemia in rats.

Moricizine (moracizine) is a new class I antiarrythmic drug which is undergoing a large scale clinical trial at present. A rat model was used to compare the effects of moricizine (5 mg/kg i.v.), disopyramide (DSP 5 mg/kg i.v.) and mexiletine (MXT 5 mg/kg i.v.) on early ventricular arrhythmias occurring within 30 min after ligation of the left coronary artery. After intravenous administration, all three drugs slowed the heart rate significantly (p less than 0.01), and compared to the control group only moricizine significantly increased the systolic, diastolic and mean arterial blood pressures. The total number of premature ventricular complexes were as follows; control group (n = 9); 1666 +/- 250 beats, moricizine group (n = 7); 1645 +/- 417 beats (NS), DSP group (n = 10); 325 +/- 155 beats (p less than 0.01 vs control) and MXT group (n = 10); 733 +/- 147 beats (p less than 0.01 vs control). The incidence of primary ventricular fibrillation, was significantly reduced by DSP and MXT (10% reduction and 20% reduction respectively) (p less than 0.05), while moricizine (incidence 80%) had no effect in comparison to the control group (incidence 90%). Death due to arrhythmia was completely abolished by DSP and MXT; although moricizine showed a slight tendency to increase the mortality rate, but the difference was not significant. In conclusion, moricizine has no obvious protective effect on early ventricular arrhythmias resulting from coronary artery occlusion in rats.

Animals↗
PubMed1992

Inhibitory effect of moricizine on reperfusion induced tachyarrhythmias in rats--a comparison study with disopyramide and mexiletine.

Acute ligation of proximal left coronary artery was performed on forty male Sprague-Dawley rats. Five min later, occlusion was released in order to evaluate the effectiveness of the 3 antiarrhythmic drugs in eliminating reperfusion ventricular arrhythmias. The drugs evaluated were moricizine (5 mg/kg), disopyramide (DSP) (5 mg/kg) and mexiletine (MXT) (5 mg/kg), which were administered intravenously 5 min before ligation of the coronary artery. Compared to control rats that underwent identical experimental procedures, all 3 drugs significantly lowered the mortality rate from 90% of the control group to 20, 20 and 0% for moricizine, DSP and MXT groups. The incidence of ventricular fibrillation (Vf) was also decreased significantly by these drugs. The duration of ventricular tachycardia (VT) and Vf of surviving rats in drug groups were 111.7 +/- 35.0 sec, 71.6 +/- 29.4 sec and 32.9 +/- 14.6 sec for moricizine, DSP and MXT, respectively. Many of the drug treated rats could be restored to the normal sinus rhythm and survived. All 3 drugs slowed the heart rate significantly, but as for the blood pressure only MXT showed significant suppressing effect. In conclusion, moricizine has the same significant preventive effect on reperfusion induced ventricular tachyarrhythmias as DSP and MXT.

Animals↗
PubMed1992

Structure and expression of the mouse angiotensinogen gene.

Angiotensinogen is a precursor of the multifunctional octapeptide hormone, angiotensin II. We have isolated the overlapping clones containing angiotensinogen gene locus from C57BL/6 mouse genomic DNA library and analyzed them by restriction enzyme mapping. The gene exhibited a structural organization similar to those of the human, rat and balb/c mouse angiotensinogen genes. Using a genomic DNA fragment of the mouse angiotensinogen gene as a probe, we have investigated the tissue distribution of angiotensinogen messenger RNA (mRNA) in C57BL/6 mouse. The angiotensinogen mRNA was highest in the liver and detectable in such tissues as brain, kidney, submandibular gland, ovary and heart. However, it was undetectable in lung and spleen under the condition used. Optimal alignments of the 5'-flanking regions among the human, rat and mouse angiotensinogen genes disclosed several deletions in the mouse sequence. To assay the promoter activity, the 5'-flanking region of the mouse angiotensinogen gene was ligated to the bacterial chloramphenicol acetyltransferase (CAT) gene, then transfected into different cultured cells. The angiotensinogen gene sequences elicited preferential expression of CAT activity when introduced into HepG2 cells derived from liver and 293 cells from kidney but not in HeLa cells from uterus, suggesting the presence of a cell type-specific promoter within the sequences. These findings on the structure and expression of the mouse angiotensinogen gene should prove useful in studying the function and control of the angiotensin.

Angiotensinogen↗
PubMed1992

[Effects of tiropramide on the activity of lower urinary tract in dogs and its interpretation].

The rhythmic contractions of urinary bladder under constant volume condition were evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve-mediated electrical and mechanical activities of smooth muscles were recorded from in vivo pelvic viscera. The vesical rhythmic contractions were transiently and partially blocked by intravenous application of tiropromide. This 'partial' block showed a good contrast to the 'complete' block of identical contractions, which was observed after application of oxybutynin, known as a potent anti-muscarinic drug. The bladder voiding cycles were observed in other decerebrate dogs, while the warmed Ringer solution was infused at a steady rate into the dome of the bladder until principal voiding contraction occurred in cystometric recordings. The initiation of voiding contraction was markedly delayed after intravenous injection of tiropramide. The delay of principal contraction was found to be due to successive appearance of falling waves in cystometric recordings. As a evident contrast, terodiline caused a significant reduction of voiding contraction height and shortening of clonic discharge phase of external urethral sphincters during voiding cycle. It is concluded that tiropramide does not reveal anti-muscarinic action which oxybutynin or terodiline does really show, instead tiropramide acts principally on bladder detrusor itself, especially on its relaxation phase of premature contraction to be prolonged. The evidences were also presented for electrophysiological identification of bladder detrusor and urethral smooth muscle.

Action Potentials↗