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Biomedical subjects

M Niwa

Publications and source records attributed to M Niwa.

At least 325 records · Page 18Linked to original sources
PubMed1990

In vitro polyadenylation is stimulated by the presence of an upstream intron.

The majority of vertebrate pre-mRNAs are both spliced and polyadenylated. To investigate the mechanism whereby processing factors recognize last exons containing both splicing and polyadenylation consensus elements, chimeric precursor RNAs containing a single intron and a poly(A) site were constructed and assayed for in vitro splicing and polyadenylation. Chimeric RNAs underwent splicing and polyadenylation. Both reactions occurred in a single RNA. The presence of an intron enhanced the rate of polyadenylation at a downstream poly(A) site. The extent of stimulation varied from two- to fivefold, depending on the magnesium concentration. Maximal stimulation of polyadenylation by an upstream intron required a 3' splice site but not a 5' splice site, suggesting that the structure of the terminal exon was more important than the presence of a complete upstream intron. We suggest that splicing and polyadenylation factors interact to recognize terminal, poly(A) site-containing exons. Such interaction may explain why all known intron-containing eukaryotic pre-mRNAs generate their 3' ends by polyadenylation.

Base Sequence↗
PubMed1990

Methotrexate cytotoxicity as related to irreversible S phase arrest in mouse L1210 leukemia cells.

The association between cytotoxicity and cell cycle perturbation caused by methotrexate (MTX) was investigated in mouse L1210 leukemia cells by flow cytometric bromodeoxyuridine/DNA assay. In the range of concentrations of MTX from 10(-7) M to 10-6) M, in vitro exposure to the drug for 6 h caused a dose-dependent suppression of clonal growth of the tumor cells and S phase arrest in the cycle progression, resulting in an accumulation of cells in early S phase, in which they showed no definite increase of DNA content above G1 levels. The surviving fraction of the clonogenic cells corresponded with the fraction of cells which recovered from the S phase arrest in MTX-free medium. In mice bearing L1210 ascites tumors, a bolus injection of MTX caused the S phase arrest of the tumor cells as shown in suspension cultures, and cytokinetic recovery was observed in parallel with the regrowth of the tumor. These results showed that irreversible S phase arrest is a critical cytokinetic event associated with the cytotoxicity of MTX.

Animals↗
PubMed1990

Thyroid hormone regulates rat pituitary insulin-like growth factor-I receptors.

As we previously obtained evidence that insulin-like growth factor-I (IGF-I) inhibits T3-induced GH secretion and GH mRNA expression without affecting basal GH secretion in thyroidectomized rat pituitary cells grown in hypothyroid medium, we examined changes in IGF-I receptors in the pituitary gland, as induced by thyroid hormone. Thyroidectomized rats and a quantitative receptor autoradiographic method were used. The density of [125I]IGF-I-binding sites in the anterior pituitary gland decreased 4 weeks after thyroidectomy; that is a significant decrease in the number of the receptors compared to findings in control rats (P less than 0.01). The affinity (Kd) remained unchanged. There were no changes in binding parameters in the ventroposterior thalamic nucleus in the brain, renal cortex, and liver parenchyma. The ip administration of T4 once a day (48 micrograms/kg) for 1-2 weeks compensated for the decrease in the binding capacity of [125I]IGF-I-binding sites to that of the control values (P less than 0.01). We propose that IGF-I receptors in the anterior pituitary gland may be regulated by thyroid hormone.

Animals↗
PubMed1990

Systemic effects of carteolol, a beta-adrenoceptor antagonist in stroke-prone spontaneously hypertensive rats.

The preventive effects of carteolol, a beta-adrenoceptor antagonist, on secondary lesions were pathophysiologically examined in stroke-prone spontaneously hypertensive rats (SHRSP) from 8 to 30 weeks of age. Carteolol was added to the drinking water in doses of 0.005% (8 to 18 weeks of age) to 0.01% (19 to 30 weeks of age) (3.8 and 6.0 mg/kg/d, respectively). These animals gained significantly more weight than the untreated control SHRSP, and their heart rate reduced from 14 weeks of age. Suppression of blood pressure rise was not definite, however, histology revealed prevention of the development or aggravation of secondary hypertension-related lesions, such as myocardial fibrosis, proliferative arteriolitis, necrotic arteriolitis and renal glomerular lesions. A decrease in non-esterified fatty acids in the serum was evident. Thus, carteolol has cardiac as well as renal protective effects, in the SHRSP.

Adrenal Glands↗
PubMed1990

Prolongation of life span of stroke-prone spontaneously hypertensive rats (SHRSP) ingesting persimmon tannin.

The effects of persimmon tannin on pathophysiological changes in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. When the persimmon tannin was chronically ingested by SHRSP, the life span was significantly prolonged, yet the effect on blood pressure was slight. The incidences of brain hemorrhage and infarction were also significantly decreased by this treatment. To elucidate the mechanisms involved in these events, the effects of condensed tannins, including persimmon tannin, on free radicals and lipid peroxidation were examined in vitro. Using electron spin resonance analysis, we found that these tannins have a potent, concentration-dependent scavenging action toward active oxygen free radicals. These tannins strongly inhibited lipid peroxidation in rat brain homogenates, in a concentration-dependent manner. Persimmon tannin inhibited lipid peroxidation similarly to (-)-epigallocatechin. Persimmon tannin was 20 times more effective than alpha-tocopherol in terms of the 50%-inhibitory concentration. The radical scavenging action and inhibition of lipid peroxidation by persimmon tannin may explain, in part, the prolongation of the life span of the SHRSP ingesting persimmon tannin.

Animals↗
PubMed1990

[Antihypertensive effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, in stroke-prone spontaneously hypertensive rats (SHRSP)].

Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of 33 +/- 1.8 mg/kg/day, orally in drinking water, throughout the experimental period. The chronic treatment with betaxolol inhibited the development of hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine, total cholesterol, free cholesterol, triglyceride, phospholipid and HDL-cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis, proliferative and/or necrotic vasculitis and glomeruli showing collapse or vasculitis in the kidneys. To shorten the time before the onset of hypertension and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% Na instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart and kidney. When betaxolol was chronically administered to SHRSP, cerebral apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the effect on blood pressure was slight. Treatment with betaxolol reduced serum creatinine levels. Our observations show that betaxolol reduces blood pressure and potently inhibits hypertensive complications in SHRSP.

Adrenergic beta-Agonists↗
PubMed1990

Evaluation of the neuroprotective action of WEB 1881 FU on hypoglycemia/hypoxia-induced neuronal damage using rat striatal slices.

Effect of WEB 1881 FU on hypoglycemia/hypoxia-induced brain damage in rats was evaluated and compared to findings obtained with idebenone. We used an in vitro model that facilitated the direct monitoring of dopamine release from striatal slices. The response to high K+ stimulation under perfusion of the slices with D-glucose-free Ringer solution (hypoglycemia) decreased at 40 min, and then practically disappeared. WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia. Hypoglycemic injury, evidenced by a remarkable neuron loss, necrosis and spongyosis was also ameliorated by these drugs. WEB 1881 FU at 10(-6) M had a protective action against the impairment of striatal responses evoked by NaCN (electron transport inhibitor at site 3) and oligomycin (inhibitor of mitochondrial ATP synthesis), but idebenone at 10(-6) M did not. In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered.

Animals↗
PubMed1990

Enzyme-linked immunosorbent assay for human insulin-like growth factor-I using monoclonal and polyclonal antibodies with defined epitope recognition.

Monoclonal antibodies (McAb) and polyclonal antibodies (PcAb) against human insulin-like growth factor-I (somatomedin C; hIGF-I) were produced. Using these two antibodies, an enzyme-linked immunosorbent assay (ELISA) system for hIGF-I was established. The ELISA system was able to detect hIGF-I at a range of 1-25 micrograms/l, compared with the range of 1-50 micrograms/l detected by radioimmunoassay (RIA). Human IGF-II and human insulin could not be recognized in this system. The plasma concentrations of IGF-I found using the ELISA agreed well with those found using RIA after conventional Sep-Pak C18 cartridge pretreatment. Epitopes of hIGF-I to McAb and PcAb were investigated by enzymatic digestion of hIGF-I followed by comparing the affinity of the antibodies to the peptides obtained proteolytically. The epitope to McAb was found to be a peptide containing Leu10-Val11-Asp12 (epitope 2). Five epitopes to PcAb containing the following key fragments were identified: a conformational structure formed by the disulphide bonds between Cys6 and Cys48, and between Cys47 and Cys52 (epitope 1), Leu10-Val11-Asp12 (epitope 2), Val17-Cys18-Gly19-Asp20 (epitope 3), Arg21-Gly22-Phe23-Tyr24 (epitope 4) and Lys68-Ser69-Ala70 (epitope 5). Of these, the peptide containing epitope 5 showed the highest affinity to PcAb. The results indicated that our ELISA system combined recognition by epitope 2 of McAb and recognition by epitope 5 of PcAb to obtain its good specificity.

Animals↗
PubMed1990

Novel endotoxin adsorbing materials, polymyxin-sepharose and polyporous polyethylene membrane for removal of endotoxin from dialysis systems.

In order to remove contaminated endotoxin from dialysis systems, we prepared and investigated two novel endotoxin adsorbing materials, Polymyxin-Sepharose (PxSeph) and polyporous polyethylene hollow fiber membrane (EHF). PxSeph was prepared by covalently immobilizing polymyxin B on Sepharose 4B beads by CNBr coupling method. It adsorbed various endotoxins with a high affinity constant and could effectively remove endotoxin from aqueous solution and human plasma. EHF also removed endotoxins from contaminated water by filtration through EHF modules, and its adsorption nature was demonstrated. Both PxSeph and EHF are stable in physiological conditions and proved to be useful adsorbents for removal of contaminated endotoxin from the hemodialysis systems.

Adsorption↗
PubMed1990

Interpretation of pathophysiology by laboratory data (3). A consultation program based on clinical laboratory data.

Based on previous studies, a consultation program using clinical laboratory data has been constructed. After converting all data into the standard deviation index (SDI), the score for preregistered diseases was calculated by integrating products of SDI and the weighting factors (WF) pre-determined empirically by medical experts for each item. Ten diseases in order of their maximum scores, the most predictable ones, and additional comments were printed out. The principle of our consultation program is based on the modified Bayesian theory which employs, instead of probability a posteriori, weighting factors (WF) corresponding to the grade of membership in the "fuzzy set" concept. Evaluations based on this interpretation performed 2-3 times during the clinical course in nine patients were found to agree qualitatively with each clinical course and diagnosis. This report also contains 1) an outline of the progress of this consultation program in Japan and abroad, 2) the actual level of acceptance of this system by physicians, 3) and the characteristics and problems of our program. We are now planning to report a quantitative evaluation of this program using many cases in some specified field, instead of one case of each disease.

Clinical Laboratory Techniques↗
PubMed1990

Detection of endotoxin antibody in long-term dialysis patients.

Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 10(8). These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophan and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers.

Antibodies↗
PubMed1990

[Impacted bilateral first permanent molars induced by the migrated second permanent molars].

It is a relatively common clinical experience to see an impacted permanent tooth. In most cases, the cause is considered to be the existence of a supernumerary tooth or developmental crowding, but occasionally, the impacted tooth may occur with no apparent cause. The tooth most frequently impacted in the dental arch is a maxillary permanent canine or the third permanent molar, but the occurrence of the first permanent molar is an extremely rare situation. The patient, an eight-year, seven-month-old male was referred to the Pediatric Dentistry Clinic at the Higashi-Nippon-Gakuen University, School of Dentistry, for a detailed dental examination of his impacted lower permanent first molars. The oral findings through dental examination revealed that the bilateral upper first permanent molars were erupted, while the lower ones showed no clinical signs of eruption. Radiographic examination revealed that the lower second permanent premolars placed under the distal root of the second deciduous molars, and the first molars, inclined to the mesial position, placed at the under the second premolars bilaterally. There was nothing particular in his medical and dental history during the "teething" period. The authors determined that the cause of this impacted condition for the first molars seemed to be induced by a migration of an unerupted second permanent premolars. After extraction of the second deciduous molars and second permanent premolars, orthodontic therapy was undertaken in an attempt to move the impacted first molars into the arch.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1990

[Evaluation of quality of life in arterial infusion chemotherapy of hepatocellular carcinoma].

We examined the quality of life in the arterial infusion chemotherapy of hepatocellular carcinoma patients using a questionnaire. The questionnaire used a category scale method of five grades. The questions about the quality of life covered ten areas for investigation (appetite, discomfort pain, nausea, daily activities, sleep, fatigue, time with family and friends, thinking about illness and confidence in the treatment). We added up scale points after one week and those after two weeks after the treatment. Patients after one-shot infusion showed aggravated scale points of anorexia and discomfort. Patients after transcatheter arterial embolization showed scale points of abdominal pain, general fatigue and discouragement about illness. Scale points in matters of thinking about illness and confidence in the treatment informed us about confidence in the course of treatment and comprehension of illness by cancer patients. How do we measure the quality of our care? This is difficult, but we thought the rate of being at home in survival might furnish us with much information in respect to the treatment and the quality of our care. In 36 patients with hepatocellular carcinoma treated with transcatheter arterial infusion and embolization, the arithmetic mean survival time after treatment was 412.1 days and time at home was 305.6 days. The rate of being at home doing survival time was 74.2% after the arterial infusion chemotherapy in 39 patients. The rate of being at home in 9 cases with one-shot infusion of Adriamycin was 43.5% (111 days); that in 9 cases with infusion of Mitomycin C microcapsules was 86.6% (716 days); that in 17 cases with transcatheter arterial embolization using spongel was 72.0% (234 days),; and that in 4 cases with infusion using implantable reservoir was 84.6% (220 days). In non-resected patients with chemotherapy, the rate of being at home was 20.3% for 61 cases of gastric cancer patients, 30.7% for 11 cases of colon cancer, 9.6% for 14 cases of gallbladder cancer and 39.8% for 112 cases of lung cancer. The arterial infusion and embolization of hepatocellular carcinoma has made it possible to lengthen the time that patients may stay home and thereby assure good quality of life.

Carcinoma, Hepatocellular↗
PubMed1990

Structure-activity relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptors.

The effects of varying the structure of philanthotoxin (PhTX) were investigated on binding of the channel blockers: [3H]perhydrohistrionicotoxin (H12-HTX) to the nicotinic acetylcholine receptor (nACh-R) of Torpedo electric organ and [3H]MK-801 [( 3H]-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten-5,10-imine maleate) to the N-methyl-D-aspartate receptor (NMDA-R) of rat brain cortex. The four moieties of PhTX (tyrosine, butyrate, spermine and the terminal amino group) were modified or conjugated resulting in 36 compounds. Although the potencies of the PhTX analogs on both receptors were higher with increasing lipophilicity and the polyamine chain length, there was considerable divergence between the two receptors' channels in the structural activity requirements for blockade by PhTX analogs. A major difference was the more critical role of the amine terminal for inhibition of the nACh-R than the NMDA-R, whereas the reverse might be true for the tyrosine moiety. The potency range of PhTX analogs on [3H]H12-HTX binding was 1070, but only 21 on [3H]MK-801 binding. Adding a lysine or arginine onto the spermine moiety increased the compound's potency on the nACh-R with little effect on the NMDA-R. Because spermine is a component of PhTX, the effects of five polyamines were also studied. Spermine and spermidine potentiated [3H]MK-801 binding, whereas putrescine, cadeverine and agmatine inhibited it. In presence of glutamate, higher concentrations of all polyamines inhibited [3H]MK-801 binding. On the nACh-R, spermine, spermidine and agmatine inhibited [125I]alpha-bungarotoxin and also [3H]H12-HTX binding in presence of carbamylcholine. The complex nature of PhTX interactions with the two receptors suggests that PhTX may bind to two sites: an external polyamine binding site and a channel binding site.

Animals↗
PubMed1989

Endothelin-triggered brain damage under hypoglycemia evidenced by real-time monitoring of dopamine release from rat striatal slices.

The role of endothelin in the pathogenesis of hypoglycemic brain damage in rats was evaluated using an in vitro model with which we could directly monitor the release of dopamine from striatal slices. There was no evidence of impairment in case of non-exposure of the slices to endothelin during 20-40 min of hypoglycemia. The response all but disappeared in striatal slices stimulated with endothelin 10(-5) M twice during 20 min of hypoglycemia. Endothelin-triggered hypoglycemic damage was not observed in the absence of extracellular Ca2+ or in the presence of nifedipine 10(-6) M. Our findings provide strong evidence that endothelin is one etiological factor in the development of hypoglycemic/ischemic brain injury, as a result of interaction with specific receptors which activate the voltage-sensitive Ca2+ channel.

Action Potentials↗