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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 523 records · Page 29Linked to original sources
PubMed1994

Alternative 5' splice site selection induced by heat shock.

The mouse HSP47 gene consists of six exons separated by five introns. Three HSP47 cDNAs differing only in their 5' noncoding regions have been reported. One of these alternatively spliced mRNAs was detected only after heat shock, which caused an alternative 5' splice donor site selection. Other stress inducers, including an amino acid analog and sodium arsenite, had no effect on the alternative splicing. The alternatively spliced mRNA, which was 169 nucleotides longer in the 5' noncoding region compared to mRNA transcribed in non-heat shock conditions, was efficiently translated under heat shock conditions. This novel finding that alternative splicing is caused by artificial treatment like heat shock will provide a useful in vivo model for understanding the exon-intron recognition mechanism as well as heat shock-induced alterations in gene expression.

3T3 Cells↗
PubMed1994

Differential effect of pharmacological autonomic blockade on some electrophysiological properties of the human ventricle and atrium.

OBJECTIVE: This study investigated the dominance of each limb of the autonomic nervous system and tested sympathetic-vagal interactions in the human ventricle and atrium after administration of propranolol and atropine. PATIENTS AND METHODS: The 90% monophasic action potential duration (MAPD90) and the effective refractory period (ERP) at the right ventricular apex (RV) and the right lateral atrium (RA) were measured in 14 patients. The MAPD90 was measured during constant RV and RA pacing (cycle length 600 ms) and the ERP was measured at a driven cycle length of 600 ms. Electrophysiological variables were measured during a control period, after propranolol (0.15 mg/kg loading dose followed by 0.1 mg/min infusion), and after autonomic blockade (atropine 0.04 mg/kg). RESULTS: Both RV MAPD90 and RV ERP increased after propranolol (RV MAPD90 from 268 (26) ms to 275 (26) ms, p < 0.005; RV ERP from 252 (25) ms to 258 (26) ms, p < 0.0005) and then decreased to below the control values after autonomic blockade (RV MAPD90 256 (24) ms; RV ERP 239 (25) ms, p < 0.0005 v propranolol, p < 0.0005 v control). In contrast, both RA MAPD90 and RA ERP increased after propranolol (RA MAPD90 from 242 (19) ms to 260 (19) ms; RA ERP from 216 (21) ms to 230 (18) ms, p < 0.0005), and then increased slightly more after autonomic blockade (RA MAPD90 265 (16) ms, p = 0.09; RA ERP 235 (16) ms, p = 0.07), thus remaining above control values (p < 0.0005). CONCLUSIONS: The results indicate (a) that in the human ventricle vagal stimulation and sympathetic beta stimulation are antagonistic and that direct vagal stimulation predominates over beta stimulation, with sympathetic-vagal interaction being minimal and (b) that in the human atrium vagal stimulation and beta stimulation are synergistic and beta stimulation predominates over vagal stimulation, with direct vagal stimulation having a minimal effect.

Action Potentials↗
PubMed1994

Plasminogen mediates an interaction between microglia and dopaminergic neurons.

Plasminogen (PGn), which was identified as a secretory product from microglia, increased dopamine uptake and the number of tyrosine-hydroxylase-expressing neurons in cultured rat mesencephalic neurons. 125I-PGn was found to bind specifically much more to mesencephalic neurons compared to other glial cells. The binding was also recognized in plasma membrane prepared from embryonic rat brain. Furthermore, ligand blotting analysis revealed that 125I-PGn binds to a 45-kD protein in plasma membrane. These results suggest that PGn-dependent neurotrophic effects may be induced through the specific binding of PGn to the 45-kD PGn-receptor-like protein in neurons.

Animals↗
PubMed1994

Coexpression of the collagen-binding stress protein HSP47 gene and the alpha 1(I) and alpha 1(III) collagen genes in carbon tetrachloride-induced rat liver fibrosis.

HSP47 is a collagen-binding stress protein and is assumed to act as a collagen-specific molecular chaperone during the biosynthesis and secretion of procollagen in the living cell. The synthesis of HSP47 has been reported to correlate with that of collagen in several cell lines. We examined the expression of HSP47 mRNA during the progression of carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Northern blot analysis revealed that the expression of HSP47 mRNA was markedly induced during the progression of fibrosis in parallel with alpha 1(I) and alpha 1(III) collagen mRNAs. By in situ hybridization, the distribution of HSP47 transcripts was similar to that of alpha 1(I) collagen and was observed only in cells lining collagen fibrils. These collagen-positive cells were confirmed to be Ito cells by immunohistochemistry for desmin. The absence of high levels of HSP47 mRNA in the liver of rats treated with only a single administration of CCl4 indicated that the induction of HSP47 mRNA was not due to the direct effect of CCl4 as a stressor, but was due to the progression of liver fibrosis. The function of HSP47 in liver fibrosis will also be discussed.

Animals↗
PubMed1994

Frontal midline theta rhythm: differentiating the physiological theta rhythm from the abnormal discharge.

The theta rhythm that appears in the frontal midline was studied morphologically and clinically in EEGs performed on 788 patients and 161 normal subjects in their late teens or older. This theta rhythm was classified into 2 types. The Type 1 theta rhythm appeared in short bursts maximally in the Fz lead and spread mainly to the anterior region. It had a high frequency, low voltage and regular waveform. The Type 2 theta rhythm appeared in long runs maximally in the Fz lead and spread mainly to the posterior areas. It had a relatively low frequency, high voltage and irregular waveform. Type 1 was observed in a younger age group (mean age: 20.3 years) that was comprised of healthy subjects and one mentally retarded patient. In no case was the Type 1 theta rhythm accompanied by a paroxysmal EEG abnormality. We therefore believe that Type 1 is a physiological EEG activity (Fm theta). On the other hand, Type 2 was observed in a relatively older age group (mean age: 30.7 years) comprised of patients diagnosed as having epilepsy or intractable headaches. Five of 9 cases showed epileptic EEG abnormalities. We therefore believe that Type 2 might have clinical significance in diagnosis of epilepsy and other cerebral dysfunctions. The EEG pattern that we call the frontal mid-line theta rhythm may be either a physiological theta rhythm or an abnormal discharge. It is possible to determine whether the theta rhythm is the former or the latter, and we believe this differentiation to be clinically important.

Adolescent↗
PubMed1994

Electrostatic cell-to-cell adhesion by a non-proteolytic component in a protease preparation.

A crude protease preparation from papaya (Protease Type III, Sigma) brought about reversible adhesion between adjacent cells of a variety of species including those of lymphoid, epithelial and fibroblastic origin at low ionic strength (below 100 mM). Sensitivities of the adhesion activity to ambient ionic strength, Ca2+, Mg2+ and pH indicated that the cell-cell contact is based on the electrostatic interaction. By ion-exchanger chromatography and gel-filtration chromatography it is suggested that the adhesion molecules in the protease preparation are dimers of cationic protein of 28 kDa distinct from the proteolytic component.

Animals↗
PubMed1994

Piperine, a pungent alkaloid, is cytotoxic to cultured neurons from the embryonic rat brain.

The present study reveals that piperine, a pungent alkaloid present in various Piper species, is cytotoxic to cultured brain neurons. Exposure to piperine (12.5-100 microM) for 72 h caused a concentration-dependent reduction in the survival of primary cultured neurons from various regions of the embryonic rat brain under high density cell culture conditions. There were relative regional differences in the susceptibility to cytotoxic effects of piperine in which septum and hippocampus showed higher vulnerability among the eight regions. The primary cultures of septal and hippocampal neurons under low density cell culture condition were performed to evaluate the contribution of non-neuronal cells. The concentration-response profiles in both high and low density cell culture conditions were comparable (septum: EC50 = 43 and 27 microM, hippocampus: EC50 = 50 and 44 microM, under high and low density cell culture conditions, respectively) suggesting a minor role of non-neuronal cells on cytotoxicity of piperine to developing neurons.

Alkaloids↗
PubMed1994

Reduction of neurite extension by piperine, examined on hippocampal and septal neurons in serum-free cultures.

The presence of piperine in a serum-free medium for 72 h markedly inhibited the neurite extension of cultured hippocampal and septal neurons under both high and low density cell culture conditions (initial cell density was 10(5) cells/cm2 and 2.5-5 x 10(3) cells/cm2, respectively). The average length of neurites decreased over a concentration range of piperine (12.5-100 microM), and the distribution of neurite population shifted towards the shorter neurite lengths whereas an increase in the soma size was observed only with high piperine concentrations (75 and 100 microM, in a high density cell culture). This indicates that the piperine effect was relatively selective to the neurite extension. The neurite extension in low density cell cultures was considerably more susceptible to piperine than that in high density cell cultures (hippocampus: EC50 = 39 versus 113 microM, septum: EC50 = 48 versus 101 microM, in the low and high density cell cultures, respectively). This difference may be due to a lack of neurotrophic supports from non-neuronal cells under the low density cell culture condition. These findings suggest that piperine, in addition to its cytotoxic effect on the neuronal survival, suppresses the neurite extension in developing neurons.

Alkaloids↗
PubMed1994

The role of the accessory pathway in the onset of atrial fibrillation in Wolff-Parkinson-White syndrome--electrophysiological examination before and after surgical ablation.

To determine the role of the accessory pathway in the pathogenesis of atrial fibrillation, we compared electrophysiological findings in 17 patients (44.7 +/- 10.2 years) with a history of atrial fibrillation before and after surgical ablation of the accessory pathway. The PA interval was shortened, and the atrial refractory periods and the potential minimal wavelength of an atrial impulse (FRPA/PA) were significantly increased, after surgery. Fragmented atrial activity (an increase of 150% or more in the duration of the high right atrial electrogram) was observed in 80% of the patients before surgery and in 25% after surgery. Its zone was significantly decreased after surgery. Repetitive atrial firing was defined as the occurrence of 3 or more successive atrial electrograms induced by a premature stimulation. This was observed in 60% of the patients before surgery, but in none after surgery. Atrial fibrillation was induced in 16 patients during the preoperative study, but in only 1 patient postoperatively. In conclusion, these results suggest that accessory pathways affect atrial vulnerability and play an important role in the onset of atrial fibrillation in WPW syndrome.

Adult↗
PubMed1994

Characterization and expression of hepatic sulfotransferase involved in the metabolism of N-substituted aryl compounds.

An aryl sulfotransferase, whose cDNA was isolated from the rat liver library, was found to catalyze bioactivation of minoxidil through N-O-sulfation and N-sulfation of a carcinogenic heterocyclic amine, IQ, by expression in COS-1 cells. cDNA of a human ortholog also was isolated and characterized as a major minoxidil-activating enzyme in human liver. Another group of aryl sulfotransferases catalyzing O-sulfation of carcinogenic N-hydroxyarylamines was separated from livers of rats and humans. These sulfotransferases have been shown to possess similar functional properties and also to relate immunochemically with each other. Current understanding on the primary structure of these sulfotransferases also is discussed.

Amines↗
PubMed1994

Changes of serum amylase, its isozyme fractions and amylase-creatinine clearance ratio in dogs with experimentally induced acute pancreatitis.

To investigate the diagnostic application of amylase to canine pancreatic diseases, serum amylase activities, its isozyme fractions and amylase-creatinine clearance ratio (ACCR) were analyzed in normal intact dogs and dogs experimentally induced acute pancreatitis. There was no statistic difference between normal male and female dogs. Amylase specific activities in pancreatic tissue extracts were more than 2,300 times higher than that in serum, and were also higher than those in other tissues; parotid and mandibular salivary glands, lung, heart, liver, spleen, duodenum, jejunum, ileum and kidney. Following the chloroform injection into the pancreatic tissue, WBC increased from 6 to 240 hr and serum glucose significantly increased at 72 and 96 hr, and no urine glucose was detected. BUN as well as serum and urine creatinine showed normal levels. ACCR increased until 96 hr without statistic significance. Serum amylase activities increased significantly after 3 hr and its isozyme was separated into 4 fractions (Amy1-Amy4) in contrast to 3 fractions (Amy2-Amy4) in intact dogs. Since this extra Amy1 seen from 1 hr increasing after 6 hr similarly to other 3 fractions, the evaluation of serum amylase and its isozyme fractions was indicated to be useful for the diagnosis of acute pancreatitis in dogs.

Acute Disease↗
PubMed1994

Sequential morphological changes of the constrictive basilar artery in a canine model of experimental cerebral vasospasm by talc injection.

To demonstrate the possible role of foreign-body reaction to extravasated blood in provoking chronic cerebral vasospasm, talc (crystallized hydrous magnesium silicate) was injected as a non-biologic foreign material into the canine-cisterna cerebellomedullaris, and pathologic changes were followed. Angiographically, this cisternal talc injection induced delayed and prolonged constriction of the basilar artery, without any evidence of so-called early phase cerebral vasospasm that should occur shortly after an insult. Pathologically, around the spastic artery in the subarachnoid space with talc injection, the appearance of a moderate cellular migration coincided with cerebral vasoconstriction, which took place 2 days after the talc injection. In the spastic basilar arterial wall, marked constrictive and degenerative changes including myonecrosis and subintimal proliferation were induced by cisternal talc injection as early as on day 2, and the changes were progressive with time. These pathologic changes were extremely analogous to those of the human autopsy cases with chronic cerebral vasospasm (chronic VS) but more prominent than those observed in the experimental autologous blood-induced model. The present study demonstrated that a foreign-body reaction to talc alone could induce chronic VS in the absence of extravasated blood. Thus, it is possible to consider that inflammatory reactions to extravasated autologous blood in subarachnoid hemorrhage may give rise to chronic VS.

Animals↗
PubMed1994

Hemodynamic effects of the calcium channel blocker pranidipine on exercise-induced angina.

Hemodynamic effects of a newly developed calcium channel blocker, pranidipine, on dynamic exercise-induced angina were investigated. Ten patients with stable effort angina pectoris underwent symptom-limited bicycle ergometer exercise testings before and after a single oral administration of pranidipine, and effects of pranidipine on systemic, cardiac and coronary hemo-dynamics induced by dynamic exercise were evaluated invasively. Pranidipine administration reduced systemic vascular resistance (from 1,764 +/- 109 to 1,115 +/- 60 dynes.sec/cm5; p < 0.01 at test, and from 1,120 +/- 102 to 795 +/- 62 dynes.sec/cm5; p < 0.05 at peak exercise) and mean arterial pressure (from 93 +/- 5 to 76 +/- 3 mmHg; p < 0.01 at test, and from 85 +/- 7 to 72 +/- 6 mmHg; p < 0.05 at peak exercise) with the increase in heart rate and cardiac index throughout exercise. Pranidipine also decreased coronary vascular resistance from 1.29 +/- 0.21 to 0.89 +/- 0.17 mmHg/ml/min (p < 0.05) at resting condition. At peak exercise, rate-pressure product and myocardial oxygen consumption decreased (from 237 +/- 21 to 215 +/- 18 x 10(2); p < 0.05, and from 31.3 +/- 7.5 to 21.7 +/- 3.9 ml/min; p < 0.05, respectively), while coronary vascular resistance did not change significantly. Furthermore, pranidipine mitigated ST-segment depression and elevation of pulmonary artery wedge pressure at peak exercise (from 0.20 +/- 0.03 to 0.13 +/- 0.02 mV; p < 0.01, and from 25 +/- 3 to 11 +/- 2 mmHg; p < 0.01, respectively). These results suggest that the major therapeutic effects of pranidipine for dynamic exercise-induced angina would be to reduce myocardial oxygen demand by improving peripheral circulation and reducing preload and afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Analysis of immune response to Helicobacter pylori--identification of the protein recognized by anti-Helicobacter pylori antibodies from sera of patients with gastroduodenal diseases].

HP-specific antibodies were measured in each collected fraction obtained from gel-filtrated separation method with selected patients sera by enzyme-linked immunosorbent assay (ELISA). Most of the fractions reacted with the patients sera also responded to HP urease-specific monoclonal antibodies. In addition, the fractions which showed urease activity strongly correlated with the HP antibody positive ones. Also, we could not detect any cross-reactivity to ureases of other species. Moreover, most patient sera strongly responded to the purified HP urease B subunit separated with SDS/PAGE by western blotting analysis. These findings suggest that the major target for HP-specific antibodies appears to be HP-urease, in particular around 68kd large molecule, urease B subunit and such urease-specific antibodies are isolate-species specific.

Adult↗
PubMed1994

[An unusual case of status epilepticus of simple partial seizure with an occipital lobe focus].

A 45-year-old man developed generalized convulsion and consciousness disturbance at age 43. An X-ray CT revealed hemorrhagic infarction in the left fronto-parieto-temporal area. A conventional angiography disclosed complete occlusion of the left cortical vein. In the chronic stage of the stroke, he had incomplete right quadrantopsia, a mild right hemiparesis and sensory aphasia. The patient has had partial somatosensory seizures since February 1990. Ictal EEG recordings showed epileptogenic discharges in the left parietal region. The seizures were adequately controlled with clonazepam. Since July 27, 1993, he has become aware of blurred vision in both eyes accompanied with headache and dizziness. On August 6, he was admitted to the hospital with right homonymons hemianopsia, sensory aphsia and tonic seizures in the right hand. Ictal EEG recordings demonstrated theta waves of the left parieto-occipital region and epileptogenic discharges in the left occipital region which consisted of spikes, sharp waves and spike-wave complexes. Single photon emission computed tomography (SEPCT) images obtained during seizures showed considerable hyperperfusion in the left occipital temporal lobes, while there was hypoperfusion in the left temporo-parietal area corresponding to the lesion of the old cerebral infarction. A T2-weighted MRI scan showed an abnormal high-intensity area in the left occipital lobe that suggested brain edema. After the admission, the patient was treated with additional anticonvulsant drugs. The tonic seizures in the right hand disappeared and right homonymous hemianopsia and sensory aphasia showed gradual improvement in the next four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Infarction↗
PubMed1994

[Clinical study of cyclic intra-arterial chemotherapy using mitoxantrone for advanced hepatocellular carcinoma].

Cyclic intra-arterial infusion chemotherapy using Mitoxantrone via reservoir system was prescribed for 8 patients with advanced hepatocellular carcinoma. According to the clinical staging system, two patients were in Stage III and the other six patients in Stage IV-A. Vp-3 portal invasion was observed in six out of the eight patients. Mitoxantrone (5-8 mg/body) was administered intra-arterially via port-a-cath device every 4 weeks. For tumor response, there were two PR cases, four NC cases, and two PD cases. Thus, the response rate was 25%. The mean survival period was 6.5 months, and 1-year survival rate was 13%. In one of two PR cases, the survival time has been more than two years so far. Gastrointestinal toxicities such as nausea and vomiting were not severe. Critical myelosuppression requiring medication was not observed. Although a temporary increase of serum bilirubin was found in two cases, no severe damage to hepatic function was observed. From our preliminary data, this arterial infusion chemotherapy using Mitoxantrone via reservoir system can be safely performed on non-hospitalized patients with advanced hepatocellular carcinoma, and may be a useful treatment modality.

Aged↗
PubMed1994

Dual action of the cyclodiene insecticide dieldrin on the gamma-aminobutyric acid receptor-chloride channel complex of rat dorsal root ganglion neurons.

The gamma-aminobutyric acidA (GABAA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide, and lindane. In order to elucidate the mechanisms of dieldrin interaction with the GABA system, whole-cell patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. When co-applied with GABA, dieldrin exerted a dual effect on the GABA-induced chloride current. The chloride current induced by 10 microM GABA was greatly enhanced by the first 20-sec co-application with 1 microM dieldrin, but the enhancement subsided during repeated co-applications, and the current was eventually suppressed below the control level. No recovery occurred after a prolonged washing with dieldrin-free solution. Desensitization of the chloride current was accelerated by dieldrin. However, when the period of co-application was limited to 2 sec, which was short enought to avoid desensitization, no suppression of current was observed during repeated co-applications and recovery occurred after washing. The desensitization and suppression occurred with an EC50 of 92 nM, whereas the enhancement required a higher EC50 at 754 nM. The GABA-induced chloride current comprised two components, one with a high sensitivity to dieldrin suppression with an EC50 of 5 nM and the other with a lower sensitivity with an EC50 of 92 nM. Dieldrin exerted its inhibitory effect on the GABA-induced current regardless of the presence or absence of pentobarbital and chlordiazepoxide. However, its effect was attenuated by the presence of picrotoxin. Furthermore, dieldrin suppressed the GABA-induced chloride current in a noncompetitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗