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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 739 records · Page 41Linked to original sources
PubMed1990

Ubiquitin-immunoreactive filamentous inclusions in anterior horn cells of Guamanian and non-Guamanian amyotrophic lateral sclerosis.

Immunohistochemical studies with an antibody to ubiquitin revealed the presence of filamentous inclusions in spinal anterior horn cells in all of six patients with Guamanian amyotrophic lateral sclerosis (ALS) and one of six cases of parkinsonism-dementia complex (PD) on Guam. Similar ubiquitin-reactive filamentous inclusions were found in all of seven non-Guamanian sporadic ALS patients examined. No similar inclusions were seen in six normal controls or in non-ALS patients who had chromatolytic neurons. The filamentous inclusions differed from spinal neurofibrillary tangles, a characteristic feature of Guamanian ALS and PD, since they were restricted to anterior horn cells and did not react with anti-tau antibody. The chromatolytic neurons of non-ALS patients occasionally had weak diffuse immunoreactivity, but no focal inclusions were detected. These results suggest that ubiquitin-reactive focal filamentous inclusions may reflect a characteristic degenerative process of anterior horn cells of motor neuron disease.

Amyotrophic Lateral Sclerosis↗
PubMed1990

Neuronal inputs to hippocampal formation in Alzheimer's disease and in parkinsonism-dementia complex on Guam.

This study concerns the expression of synaptophysin in the hippocampal formation of normal controls, of patients with Alzheimer's disease (AD) and of patients with parkinsonism-dementia complex on Guam (P-D complex). A monoclonal antibody was used to visualize synaptophysin, an integral component of presynaptic vesicle membranes. In the normal controls, a strong synaptophysin immunoreactivity was seen in the stratum pyramidale, stratum radiatum and stratum lacunosum-moleculare of the hippocampus proper, in the subiculum and in the molecular layer of the dentate gyrus. In the dentate gyrus molecular layer, the reaction product was distributed in a laminar fashion. By contrast, in AD and in P-D complex a significant decrease in immunoreactivity was observed in all hippocampal strata, and especially of the hippocampal subfield CA1 and the subiculum. In both diseases, synaptophysin expression was also diminished in the molecular layer of the dentate gyrus of all patients examined, with the inner portion exhibiting almost normal and the outer portion a strikingly reduced synaptophysin immunoreactivity.

Adult↗
PubMed1990

Inhomogeneity of the putaminal lesion in striatonigral degeneration.

An immunohistochemical topographic study was carried out in the putamen from three patients with striatonigral degeneration (SND) using antibody to calcineurin (CaN), a neurochemical marker for the striatal medium-size spinous neurons. In patients with SND, there was significant depletion of CaN immunoreactivity in the putamen with the caudal and lateral portion of the putamen being consistently and severely affected. In addition, the SND patients showed an inhomogeneous distribution pattern of residual CaN staining in the putamen, where remaining CaN immunoreactivity appeared as a characteristic patchwork of "islands" resembling the "striosomes" observed by the tyrosine hydroxylase or Met-enkephalin immunostaining in the putamen from normal individuals. This finding may account for the fact that there are subregional and compartmental differences in susceptibility of the medium-sized spinous neurons in the putamen with SND.

Adult↗
PubMed1990

A comparative immunohistochemical study on striatal Met-enkephalin expression in Alzheimer's disease and in progressive supranuclear palsy.

Using a sensitive immunoperoxidase technique we examined Met-enkephalin (MEnk) expression in the striatum and globus pallidus external segment (GPe) from patients with Alzheimer's disease (AD) and with progressive supranuclear palsy (PSP). In AD patients strong MEnk-like immunoreactivity was persistent in the striatum showing so-called "striosomes". In addition, a number of typical "woolly fibers" were observed in the GPe. MEnk-positive striosomes were also visible in the striatum of PSP patients and were similar to those of normal controls and of AD patients. However, the MEnk-positive "woolly fibers" appearance was less well recognizable in the GPe from all the PSP patients examined.

Alzheimer Disease↗
PubMed1990

Alteration of aminoacyl-tRNA synthetase with age: heat-labilization of the enzyme by oxidative damage.

Active oxygens have been suggested to be involved in age-related alterations of organelles and molecules. In this study we investigated the influence of active oxygen on aminoacyl-tRNA synthetases partially purified from rat liver. Treatment of leucyl-tRNA synthetase with Fe3(+)-ascorbate resulted in the increased heat-lability of the enzyme. The inactivation was inhibited by radical scavengers such as mannitol and benzoate, suggesting that hydroxyl radicals are responsible for heat-labilization of the enzyme. On the other hand, a considerable part of tyrosyl-tRNA synthetase was converted to heat-labile forms without added iron and ascorbate under aerobic conditions but not under anaerobic conditions. These and other findings suggested that the heat-labilization of this enzyme is caused by active oxygens probably generated by the reaction of dioxygen and transition metal ions present in the enzyme preparations. Heat-inactivation curves of the enzymes modified as described above were similar to those observed for the enzymes from aged animals in that these enzymes exhibited higher percentages of heat-labile forms than the unmodified enzymes from young animals [Takahashi and Goto, 1987, Arch. Gerontol. Geriatr. 6, 73-82; Takahashi and Goto, 1987, Arch. Biochem. Biophys. 257, 200-206]. The present findings are consistent with the theory that active oxygens are involved in the age-related alterations of enzymes.

Aging↗
PubMed1990

Effect of dietary restriction on the degradation of proteins in senescent mouse liver parenchymal cells in culture.

We previously reported that the half-life of protein degradation in cells from old mice is about 50% longer than that in cells from young or middle-aged ones. In the present study we investigated the degradation rate of microinjected proteins (horseradish peroxidase (HRP) and ovalbumin (OVA] and pulse-labeled proteins in hepatocytes from dietary-restricted old mice. Dietary restriction was initiated when mice were 23 months of age and performed in two steps (first 80% and then 60% of the ad libitum intake), the total period being 70 days. Hepatocytes were isolated from mice fed a restricted diet and fed ad libitum. The half-lives of HRP, OVA, and pulse-labelled proteins in the hepatocytes from mice fed a restricted diet were about 40% shorter than those in the cells from mice fed ad libitum. These values were close to those in the cells of young animals. These results are discussed in relation to our previous findings that a similar regimen reduces the percentage of heat-labile enzymes accumulated in tissues of aged animals.

Aging↗
PubMed1990

Cholesterol-lowering activity of various undigested fractions of soybean protein in rats.

The undigested high-molecular-weight fraction (HMF) of soybean protein prepared after exhaustive digestion by microbial proteases significantly decreased serum cholesterol levels to approximately 45% (p less than 0.05) of those observed with the parent protein in rats fed diets containing cholesterol (0.5%) and sodium cholate (0.125%). HMF bound conjugated bile salts in vitro and significantly increased fecal excretion of both neutral and acidic steroids by 65-95% and 80-170% more, respectively (p less than 0.05), than did the intact protein. Extraction of HMF with methanol slightly decreased the activity, but the methanol-soluble fraction was not regarded as a principal determinant. Soybean saponin at the dietary level equivalent to that contained in HMF did not effectively lower serum cholesterol. The activity was not necessarily duplicated even when methanol-treated fractions were recombined. Further degradation of the methanol-extracted HMF by various proteases resulted in loss of activity. HMF obtained after pepsin digestion exerted a potential similar to that of HMF prepared after digestion by microbial proteases.

Animals↗
PubMed1990

State of binding subsites in Asp 101-modified lysozymes.

The environments of the binding subsites in Asp 101-modified lysozyme, in which glucosamine or ethanolamine is covalently bound to the carboxyl group of Asp 101, were investigated by chemical modification and nuclear magnetic resonance spectroscopy. Trp 62 in each of the native and the modified lysozymes was nitrophenylsulfenylated. The yield of the nitrophenylsulfenylated derivative from the lysozyme modified with glucosamine at Asp 101 (GlcN-lysozyme) was considerably lower than those from native lysozyme and from the lysozyme modified with ethanolamine at Asp 101 (EtN-lysozyme). These results suggest that Trp 62 in GlcN-lysozyme is less susceptible to nitrophenylsulfenylation. Kinetic analyses of the [Trp 62 and Asp 101]-doubly modified lysozymes indicated that the nitrophenylsulfenylation of Trp 62 in the native lysozyme, EtN-lysozyme, or GlcN-lysozyme decreased the sugar residue affinity at subsite C while increasing the binding free energy change by 2.7 kcal/mol, 1.5 kcal/mol, or 0.1 kcal/mol, respectively. Although the profile of tryptophan indole NH resonances in the 1H-NMR spectrum for EtN-lysozyme was not different from that for the native lysozyme, the indole NH resonance of Trp 62 in GlcN-lysozyme was apparently perturbed in comparison with that of native lysozyme. These results suggest that the environment of subsite C in GlcN-lysozyme is considerably different from those in native lysozyme and EtN-lysozyme. The glucosamine residue attached to Asp 101 may contact the sugar residue binding site of the lysozyme, affecting the environment of subsite C.

Amino Acid Sequence↗
PubMed1990

Susceptibility to tourniquet-induced radial palsy in the presence of previous humeral fracture.

The purpose of this article is to present a potential hazard that may be encountered when using a pneumatic tourniquet during hand surgery, even when applied with the appropriate pressure and for the correct amount of time. Two of our patients developed complete radial nerve paralysis after hand surgery in which the pneumatic tourniquet was used. The tourniquet had a manometer between the cuff and the pump, which allowed for pressure control. The tourniquet time for patient 1 was 45 minutes and for patient 2 65 minutes, and the pressure was 250 mm Hg in both. Both patients had a history of humeral fracture on the paralyzed side.

Adult↗
PubMed1990

Immunohistochemical evidence for the selective involvement of dorsal root fibres in Friedreich's ataxia.

An immunohistochemical study was carried out in order to elucidate the selective involvement of the dorsal root fibres from two patients with Friedreich's ataxia in comparison with those of 10 neurologically normal control individuals. For this purpose, antibodies to substance P and to synaptophysin were used. Substance P-immunoreactive unmyelinated fibres forming a dense network in the normal substantia gelatinosa of the spinal dorsal horn predominantly originate from a subpopulation of small cells of the dorsal root ganglia, while synaptophysin is present in virtually all nerve cell axon terminals and is useful for visualizing axon terminals in the nervous system. Strong substance P-like immunoreactivity was seen in the substantia gelatinosa of patients with Friedreich's ataxia. By contrast, there was marked depletion of synaptophysin immunoreactivity in the posterior column nuclei, with the gracile nucleus showing greater loss of positive puncta than the cuneate nucleus.

Adult↗
PubMed1990

Result of immunotherapy on patients with unexplained recurrent abortion: a beneficial treatment for patients with negative blocking antibodies.

Thirty-nine unexplained recurrent aborters underwent vaccination using husband's lymphocytes according to the previously reported protocol. No mixed lymphocyte culture reaction-blocking antibodies (MLR-BAbs) were observed in these patients prior to vaccination. Of 35 newly pregnant patients after vaccination(s), pregnancy successfully continued in 28 (80.0%) and have already been terminated with a liveborn offspring. Pregnancy outcome was also analyzed in unexplained recurrent aborters who revealed positive MLR-BAbs without immunotherapy. In this group, out of eight pregnancies in seven patients, five (62.5%) continued beyond their critical period of 14 wks of gestation. Three infants born from these pregnancies, however, presented severe abnormalities. Furthermore, outcome of 14 pregnancies in 12 unexplained recurrent aborters with negative MLR-BAbs was analyzed since they had become pregnant without immunotherapy; pregnancy was successfully continued in only four cases (28.6%). Thus, vaccination using husband's lymphocytes on unexplained recurrent aborters with negative MLR-BAbs is suggested to be effective. In addition, it is suggested that immunotherapy for patients with positive MLR-BAbs should be carefully followed.

Abortion, Habitual↗
PubMed1990

Spinal cord neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis and parkinsonism-dementia complex: an immunohistochemical study.

We studied the topographic distribution and immunohistochemical characteristics of spinal cord neurofibrillary tangles (NFTs) in 6 patients with Guamanian amyotrophic lateral sclerosis (ALS) and 6 patients with parkinsonismdementia complex (PD) on Guam, using antibodies to tau protein and ubiquitin. The NFTs were immunoreactive with both antibodies, but staining for tau was more pronounced. As identified by this reactivity, all the Guamanian ALS and PD cases examined showed spinal cord NFTs. The posterior horn had the most and the anterior horn the least. In the posterior horn the NFTs were located mainly in the marginal areas. Large anterior horn cells showed few, if any, NFTs. In addition to perikaryal NFTs, we observed tau-reactive neurites. Our results provide evidence that spinal cord NFTs are not uncommon in Guamanian ALS and PD on Guam and that they are more numerous than previously found with conventional methods.

Adult↗
PubMed1990

Met-enkephalin immunoreactivity in the basal ganglia in Parkinson's disease and striatonigral degeneration.

This study concerns the expression of Met-enkephalin (MEnk) in the striatum and the external segment of the globus pallidus proper (GPe) in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). For this purpose, we developed a sensitive immunoperoxidase technique to visualize MEnk-positive patches in routinely prepared formalin-fixed paraffin-embedded striatal tissues. In comparison with normal controls, MEnk-positive patches and pallidal MEnk-positive axon terminals were strongly present in patients with PD, showing characteristic distribution patterns. By comparison, in SND patients, there was striking diminution of MEnk staining in the putamen and ventrolateral portion of the GPe, while MEnk patches were persistent in the caudate nucleus.

Aged↗
PubMed1990

Pharmacological evaluation of hydroxypropylcellulose-ethylcellulose microcapsules containing piretanide.

Hydroxypropylcellulose (HPC)-ethylcellulose (EC) microcapsules containing piretanide prepared by a solvent evaporation technique, were evaluated on pharmacokinetic, pharmacodynamic and pharmacological parameters in spontaneously hypertensive rats (SHR). HPC-EC10 (5:3) microcapsules showed sustained plasma piretanide levels and almost the same AUC (area under the curve) as compared with piretanide solution. Effect of treatment with the microcapsules (single oral administration per day in doses of 10 and 30 mg/kg) and the solution (double oral administration per day in doses of 5 and 15 mg/kg) was examined for 4 weeks on urine volume and urinary electrolytes excretion and blood pressure. The microcapsules and solution induced dose-dependent diuresis throughout the experimental period and a reduction in blood pressure from 2 weeks of the treatment. HPC-EC10 (5:3) microcapsules containing piretanide were satisfactory as a sustained-release preparation in the light of the anti hypertensive effect even at a half frequency of daily dosing of the solution.

Administration, Oral↗
PubMed1990

Synthesis of valproyl-2-pyrrolidinone and its evaluation as a cognitive drug with the ability to modulate acidic amino acids in the brain.

A new pyrrolidinone derivative, valproyl-2-pyrrolidinone (VP), was synthesized, followed by evaluation as a cognitive drug. VP gave rise to a significant protective effect against cerebral anoxia together with a potent prolongation of latency time for the reversal of scopolamine induced transient disruption of the memory of a passive avoidance response in rats. The quantitative experiment using HPLC demonstrated a significant reduction of hippocampal aspartate (Asp) and glutamate (Glu) following the intraperitoneal administration of VP at a dose of 300 mg/kg.

Administration, Oral↗