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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 721 records · Page 40Linked to original sources
PubMed1992

Mass spectrometry in the integrated strategy for the structural analysis of protein variants.

A significant proportion of genetic disorders are caused by point mutations in proteins, and many variants of haemoglobin have been characterized by mass spectrometry. The strategy employs fast atom bombardment and/or tandem mass spectrometry of enzymatically digested peptides for elucidating the type and position of the mutations. Electrospray ionization mass spectrometry is useful for detecting mutations in the intact protein molecule, but the competence diminishes with increasing mass or increasing number of 13C atoms. Recent developments of DNA techniques requires us to re-evaluate the status of mass spectrometry in this field. The role of mass spectrometry in the structural analysis of protein variants is discussed, and is compared with chemical methods and DNA strategies.

Amino Acid Sequence↗
PubMed1992

Experimental and clinical evaluation by flow cytometry for the mechanism of combination therapy (cisplatin and peplomycin).

Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell kinetics were studied both in vitro and in vivo with the aid of flow cytometry (FCM). Double staining with propidium iodide (PI) and fluorescein isothiocyanate (FITC)-labeled bromodeoxyuridine (BrdU) was used to analyze the cell cycle, and the number of viable cells was determined with fluorescein diacetate (FDA). Effects of combining the 2 agents were also studied to establish the most effective method of combination therapy. Furthermore, these agents were tried clinically on the basis of experimental results. Results showed that CDDP exerted its action at the S and G2M phases in the cell cycle and PEP at the G2M phase. Among the combination regimens in the experiments with CDDP, PEP, and CDDP + PEP as analyzed by FCM, the strongest block on the G2M phase was shown in the one at a 2-day interval, resulting in the most effective killing of the tumor cells. Clinical trial of the combination therapy showed the same results as the in vitro experiment; the therapy proved useful for improving the patient's clinical condition and the results obtained with CT imaging and pathology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Electrospray ionization mass spectra of hemoglobin and transferrin by a magnetic sector mass spectrometer. Comparison with theoretical isotopic distributions.

Electrospray ionization mass spectra of human hemoglobin chains and of transferrin were acquired on a magnetic sector mass spectrometer. The observed molecular ion for each hemoglobin chain was in good agreement with the theoretical isotopic distribution at a reasonable resolution of 2000. The clear separation of a variant beta-chain in admixture with the normal counterpart at mass 15,867 that differed from it by 14 Da (0.09%) ensured that a smaller mass difference could be detected. The molecular ions for human transferrin were too broad compared with the theoretical shape to determine the molecular mass accurately, probably due to the heterogeneity of the carbohydrate moiety. A decrease in mass by neuraminidase digestion, however, determined the average number of sialic acids in the molecule.

Hemoglobins↗
PubMed1992

Anticonvulsant effect of allopurinol on hippocampal-kindled seizures.

This study assessed the anticonvulsant effect of allopurinol (5 and 50 mg/kg, IP) on seizures kindled from the feline hippocampus. Allopurinol at a higher dose significantly reduced the behavioral seizures stage, but not afterdischarge duration, without producing any behavioral toxicity. The present results lend experimental support to the contention that allopurinol possesses anticonvulsant efficacy in the treatment of human epilepsy.

Allopurinol↗
PubMed1992

The NMDA receptor antagonist MK-801 has a dissociative effect on seizure activity of hippocampal-kindled cats.

This study assessed the behavioral and electrographic effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate (MK-801) (0.1 and 0.5 mg/kg, IP), a noncompetitive antagonist of the NMDA receptors, in hippocampal (HIP)-kindled cats. MK-801 at a higher dose significantly reduced the afterdischarge duration, but not the behavioral seizure stage, of HIP-kindled seizures. This anticonvulsant effect occurred in association with the appearance of severe behavioral toxicity and paradoxical worsening of background electroencephalogram characterized by profound spike and wave discharges. The present data suggest the dissociative effect of MK-801 on seizure activity and limitations of its clinical utility as an antiepileptic agent.

Animals↗
PubMed1992

Telescience testbed for biomedical experiments in space morphological and physiological experiments of rat musculoskeletal system.

As the second telescience testbed experiment we were examined sophisticated processes of biomedical experiment, such as an implantation of a transmitter into the hamster's abdominal cavity, non-stressful blood sampling, large amount of blood collection, muscle extirpation and biopsy from the hamsters on February 6-8, 1990. To make clear the differences between successful results obtained by an experienced hand and by a non-experienced one, three operators were selected for three successive experimental days; an engineer who had never experienced any biological experiment, a non-biology student, who experienced on biological experiments, and a veterinary surgeon. Surgical procedures need much experiences on maneuvering and understanding of theory to shorten the elapse time. Especially for a non-experienced hand, graphic instructions were much helpful to understand and to maneuver the procedures. Continuous recordings of ECG from a operator and PIs were of an advantage to grasp an extent of the mental strain, which was compared with their reports requested after end of each experimental day. The mental strain was not related to degrees of scientific achievement, but showed faithfully difficulty of each experimental procedure. Training effects on PIs in successive experimental days were found in their instructions for the operator to let understand the procedures.

Animals↗
PubMed1992

Neonatal cerebral infarction: symptoms, CT findings and prognosis.

In a retrospective multi-center study, we investigated eighteen infants with unilateral cerebral infarctions confirmed by computed tomography (CT) scans. The initial symptoms were observed in all the patients between 0 and 3 days of age. Convulsions or apneic attacks were the initial symptoms in all but one. Only 4 patients had complicated obstetric histories and none showed polycythemia or electrolyte abnormalities. All of the initial CT scans revealed unilaterally localized hypodense areas. In 10, the initial CT scans were performed within 24 hours after the clinical onset. In 16, the lesions were within the territory of the middle cerebral artery, 9 of which also involved the cortico-spinal tract (CST). In the remaining 2 patients, the lesions were located within the territory of the posterior cerebral artery. None of the 9 patients without CST involvement developed hemiplegia, whereas 5 (56%) of the 9 with CST involvement had hemiplegia, which is a fairly low incidence compared with that in adult cases. This difference was thought to be related to neonatal brain plasticity.

Cerebral Infarction↗
PubMed1992

Atrial contractility affects phasic blood flow velocity of atrial small vessels in the dog.

OBJECTIVES: The aim was to evaluate the relative contribution of atrial muscle contraction and atrial pressure to the phasic patterns of left atrial arterial and venous flows. METHODS: Using a laser Doppler velocimeter, blood velocities were measured in the atrial small arteries and veins (outer diameter: 150-500 microns) in anaesthetised open chest dogs (n = 21). The velocity sensor was fixed on the vessel surface with a drop of cyanoacrylate glue when good quality Doppler signals were consistently observed. Left atrial pressure and the contractility of the left atrium were changed by premature ventricular contraction and by intracoronary injection of isoprenaline (0.5 microgram), respectively. RESULTS: Premature ventricular contraction increased left atrial pressure significantly during arterial velocity measurements from 8.1(SD 2.7) to 16.4(1.3) mm Hg and during venous measurements from 8.2(1.2) to 14.3(3.7) mm Hg. However, premature ventricular contraction did not change the blood velocity patterns, the maximum deceleration rate of the systolic velocity wave in arteries, or the maximum acceleration rate of the systolic velocity wave in veins. Although isoprenaline did not change the left atrial pressure, it decreased minimum arterial blood velocity during atrial systole, from 3.3(3.4) to -2.5(3.2) cm.s-1, and increased maximum venous blood velocity from 15.9(5.5) to 19.2(7.4) cm.s-1. Isoprenaline also increased both the maximum arterial systolic velocity deceleration rate, from 90(45) to 234(143) cm.s-2, and the maximum venous systolic velocity acceleration rate from 356(230) to 763(366) cm.s-2. CONCLUSIONS: (1) Left atrial pressure is not a major determinant of the blood flow patterns of the atrial arteries and veins, and therefore it may not closely reflect pressure around mural vessels. (2) Atrial contractility affects the blood flow patterns of the atrial arteries and veins.

Animals↗
PubMed1992

Mitotic activity in mice is suppressed by energy restriction-induced torpor.

We monitored core body temperature by telemetry in energy-restricted (201 kJ/wk) and control (397 kJ/wk) C57BL/6 and SHN/C3H F1 mice to determine whether torpor may be involved in the suppression of mitotic activities resulting from energy restriction. The energy restriction regimen employed inhibited the development of cancer and greatly extended longevity in both these mouse strains. Male and female C57BL/6 mice subjected to energy restriction from 4 wk of age and tested at 3 mo of age became torporific (body temperature less than 31 degrees C) at ambient air temperatures of 20-22 degrees C, whereas control animals stayed euthermic (greater than 35 degrees C). Energy restriction also induced torpor in 3- and 13-mo-old SHN/C3H F1 female mice, whereas 3-, 13- and 24-mo-old control mice were euthermic. Energy restriction decreased mitotic activities to approximately 30% of control values in both jejunum and epidermis in 3-mo-old female C57BL/6 mice maintained at 20-22 degrees C. However, this suppression of mitotic activities was antagonized by housing the energy-restricted mice at 30 degrees C for 2 wk, indicating that torpor plays a substantial role in suppressing mitotic activities in energy-restricted mice.

Animals↗
PubMed1992

Purification and characterization of formaldehyde dehydrogenase from rat liver cytosol.

Formaldehyde dehydrogenase was purified to electrophoretic and column chromatographic homogeneity from rat liver cytosolic fraction by a procedure which includes ammonium sulfate precipitation, DEAE-cellulose-, hydroxyapatite-, Mono Q-chromatography, and gel filtration. Its molecular mass was estimated to be 41 kDa by gel filtration and SDS-PAGE, suggesting that it is a monomer. It utilized neither methylglyoxal nor aldehydes except formaldehyde as a substrate. It has been reported that liver class III alcohol dehydrogenase and formaldehyde dehydrogenase are the same enzyme and oxidize formaldehyde and long chain primary alcohols. However, the enzyme examined here did not use n-octanoi as a substrate. The Km values for formaldehyde and NAD+ were 5.09 and 2.34 microM at 25 degrees C, respectively. The amino acid sequences of 10 peptides obtained from the purified enzyme after digestion with either V8 protease or lysyl endopeptidase were determined. From these results, the enzyme was proved to be different from the previously described mammalian formaldehyde dehydrogenase and is the first true formaldehyde dehydrogenase to be isolated from a mammalian source.

Aldehyde Oxidoreductases↗
PubMed1992

Neuroradiological findings in glutaric aciduria type I: report of four Japanese patients.

We examined neuroradiological computerized tomography (CT) findings and the clinical course of four Japanese children with glutaric aciduria type I (GA1) whose enzyme activity of glutaryl-CoA dehydrogenase was undetectable. Brain CT in all cases examined showed low density white matter, fluid collection in bilateral frontotemporal regions (particularly surrounding the Sylvian fissures), enlargement of the lateral ventricles and slight atrophy of the basal ganglia. Although these findings seemed to be characteristic for GA1, they were unlikely to be more extended, at least over 2 years after infancy. The low density white matter was observed more evidently in the neonatal or early infantile periods than in later periods. The degree of enlargement of fissures in bilateral frontotemporal regions about the Sylvian fissures appeared to correlate with the severity of symptoms such as dystonia or choreoathetosis. Magnetic resonance images (MRI) in one case showed bilateral linear-shaped low intensity in areas of the external capsules and putamen on a T1-weighted image. These CT and MRI findings, as well as clinical symptoms such as choreoathetosis or dystonia, may suggest that metabolic abnormalities in GA1, such as glutaconate, are toxic to the extrapyramidal tract system in the central nervous system, and that the clinical symptoms of the patients are attributable to atrophy of basal ganglia. Brain CT may be useful in diagnosis and evaluation of the clinical course of GA1 patients.

Brain↗
PubMed1992

[Clinical studies on pediatric purulent meningitis--clinical symptoms and prognosis].

In 149 patients with purulent meningitis we encountered in the period of 20 years from 1970 to 1990, their clinical symptoms and prognosis were investigated. Death or sequela was noted in many of the patients having loss of consciousness, stiffness of the members and/or cyanosis as primary clinical symptoms, or having hypoalbuminemia (less than 2.5 g/dl) and/or thrombocytopenia as abnormal laboratory findings, or having excessive protein levels and/or excessively low sugar levels in cerebro-spinal fluid. Early initiation of adequate antibiotic therapy, as well as symptomatic treatment using transfusion, steroids and anticonvulsants, are important.

Female↗
PubMed1992

[Clinical studies on pediatric purulent meningitis--statistical analysis of etiology and therapy].

In a total of 149 children with purulent meningitis we encountered in our institute in the last 20 years, the causatives, the changes in therapeutic management and the prognosis were investigated. The causatives could be detected in 109 patients (73%): H. influenzae; 30 patients (20%), S. pneumoniae; 18 patients (12%), E. coli; 13 patients (9%), GBS; 7 patients (5%) and S. aureus; 6 patients (4%). These five causatives were detected in 49% of the total patients, or 67% of the patients in whom causatives could be detected. Of these five causatives, E. coli were detected the most frequently in the first half of 1970's, but, in recent years, the detection of GBS, S. pneumoniae and H. influenzae has been remarkably increasing. In spite of progress in antibiotics, the prognosis of the disease due to S. pneumoniae, GBS and S. aureus was poor. In the majority of the patients who died, the death came within five days after hospitalization due to loss of consciousness, convulsion etc. It is therefore necessary not only to initiate strong antibiotic treatment as soon as possible after early diagnosis, but also to take symptomatic measures such as steroidal treatment, treatment of shock etc.

Anti-Bacterial Agents↗
PubMed1992

Serotonergic inhibition of limbic and thalamic seizures in cats.

To clarify the role of the serotonergic system in limbic and thalamic epileptic activity, we examined the effects of 5-hydroxytryptophan (5-HTP, 20 and 40 mg/kg) on fully kindled seizures from the hippocampus and lateral geniculate nucleus. The intraperitoneal administration of 20 mg/kg 5-HTP exerted no anticonvulsant effect on hippocampal kindled seizures, and a higher dose (40 mg/kg) produced a significant reduction in the behavioral seizure stage. 5-HTP at 20 mg/kg displayed no suppressive effect on lateral geniculate seizures, and 5-HTP at 40 mg/kg significantly reduced both the seizure stage and afterdischarge duration. Our data suggest that serotonergic mechanisms play an inhibitory role in seizures kindled from these brain regions.

5-Hydroxytryptophan↗
PubMed1992

The rabbit syndrome and antiparkinsonian medication in schizophrenic patients.

Effects of antiparkinsonian medication on the rabbit syndrome (RS) and accompanying parkinsonian symptoms were studied in 5 schizophrenic inpatients receiving long-term antipsychotic medication. All patients showed early improvement of RS following additional treatment with trihexyphenidyl or biperiden, with a significant reduction in the RS score also observed. The improvement of RS paralleled improvement of the parkinsonian symptoms, with the score of the Simpson-Angus rating scale significantly reduced. Our data provide further evidence that the underlying mechanism of RS is similar to that of acute forms of drug-induced parkinsonism.

Adult↗
PubMed1992

Action of the N-methyl-D-aspartate receptor antagonist MK-801 against focal seizure activity from the feline hippocampus.

This study assessed the effects of MK-801 (0.1 and 0.5 mg/kg), a noncompetitive antagonist of N-methyl-D-aspartate receptors, on focal seizure activity elicited by electrical stimulation to the feline hippocampus. Neither afterdischarge duration nor behavioral seizure stage was significantly suppressed following intraperitoneal administration of MK-801 at two dose. Rather, MK-801 at a higher dose induced hippocampal seizure status in some of the cats tested. The present data suggest convulsant properties of MK-801 and limitations of its clinical utility as an antiepileptic agent.

Animals↗