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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 829 records · Page 46Linked to original sources

Brain-gut induction of heat shock protein (HSP) 70 mRNA by psychophysiological stress in rats.

Restraint water-immersion stress-induced expression of heat shock protein (HSP)70 mRNA in the cerebral cortex and stomach of rats was evaluated by Northern blotting. Cerebral and gastric HSP70 mRNA significantly increased in the 6 h-stressed rats and the amount of mRNA measured as optical densities was highest in the 12 h-stressed rats. These data confirmed our previous observations and suggest that families of HSPs play a salient cytoprotective role in stress-vulnerable organs.

Animals↗

Immunosuppressive activity of cloned natural killer (NK1.1+) T cells established from murine tumor-infiltrating lymphocytes.

To elucidate the role of NK1.1+ T cells in the antitumor immune response, we established cloned NK1.1+ T cell lines from tumor-infiltrating lymphocytes (TIL) of B16 melanoma, and examined their mode of action in generating antitumor effector T cells both in vitro and in vivo. An NK1.1+ T cell clone (TM4.2) was phenotypically CD3+ TCR-alphabeta+ CD4- CD8- NK1.1+, and CD28+. The TM4.2 cells suppressed the in vitro generation of anti-B16 melanoma CTLs, but not the effector function of CTLs. The results using a transwell membrane suggested that their suppressive activity was mediated by both soluble factors and a direct cell to cell interaction. As for the soluble factors, the suppressive activity of the culture supernatant of TM4.2 cells was neutralized by anti-TGF-beta mAb, and the TM4.2 cells actually produced a considerable amount of TGF-beta. On the other hand, the TM4.2 cells showed a high level of cytolytic activity against B cell blasts and CD80-transfected P815, and such cytolytic activity was reduced by the addition of anti-CD80 mAb. In addition, NK1.1+ T cells in the freshly isolated TIL were revealed to express CD28. Furthermore, the TM4.2 cells suppressed the in vitro generation of anti-allo CTLs irrespective of the MHC haplotype. Finally, the TM4.2 cells suppressed the in vivo antitumor immune response. Collectively, these findings demonstrate that NK1.1+ T cells in TIL show immunosuppressive activity in the antitumor immune response through the production of TGF-beta and the preferential cytolysis of B7-expressing cells.

Animals↗

Effect of serum cholesterol levels on meta-chlorophenylpiperazine-evoked neuroendocrine responses in healthy subjects.

This study was undertaken to test the hypothesis that serum cholesterol levels might be associated with serotonergic receptor function. The participants were 10 healthy male subjects. After an overnight fast, the subjects received meta-chlorophenylpiperazine (m-CPP) or identical placebo capsules orally in a randomized, double-blind, cross-over design. Blood was obtained for measurement of prolactin, cortisol, adrenocorticotropic hormone (ACTH), and cholesterol. There were some significantly positive correlations between serum cholesterol levels and hormonal responses to m-CPP administration. These results suggest that serum cholesterol levels may be positively associated with serotonergic receptor function.

Adrenocorticotropic Hormone↗

Cognitive function in amyotrophic lateral sclerosis.

Cognitive function in patients with amyotrophic lateral sclerosis (ALS) has drawn recent attention. However, the pathogenesis of cognitive dysfunction in patients with ALS remains uncertain. To explore the underlying mechanism for cognitive dysfunction further, we studied 26 patients with ALS (15 male and 11 female; age from 36 to 67 years) by using neuropsychological batteries, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). We also evaluated these patients and an additional 26 age- and sex-matched normal controls using neuropsychological batteries with special attention to the frontal lobe function. On the basis of neuropsychological examination, we classified patients into three groups using cluster analysis. Age, education level and severity were comparable across these subgroups. Neuropathologic examination was subsequently carried out in six patients. Patients in Group 1 and 2 had low scores on all measures compared to patients in Group 3 and normal controls. Patients in Group 1 and 2 had frontal atrophy on MRI and reduced isotope uptake in the frontal region on SPECT, which was more evident in patients in Group 1. On neuropathologic examination, patients in Group 1 showed spongy degeneration and neuronal loss in the frontal lobe. Patients in Group 3 showed no notable pathology in the frontal region. The gradient distribution of the scores for attention and executive function, as well as SPECT findings suggested the presence of a continuum of cognitive disability in patients with ALS corresponding to the pathologic process in the frontal lobe ranging from significant impairment to normality. We, therefore, believe that inattention and executive dysfunction alternatives may evolve in patients with ALS corresponding to the pathologic process in the frontal lobe.

Adult↗

Dissociative expression of adenoviral-mediated E. coli LacZ gene between ischemic and reperfused rat brains.

A replication-defective adenoviral vector containing the E. coli lacZ gene was directly injected into the ischemic or reperfused cerebral cortex of rats. An administration of adenoviral vector showed a slight to moderate expression of the lacZ gene in the cerebral cortex of the middle cerebral artery (MCA) region until 2 days after the MCA occlusion. In contrast, expression of the lacZ gene was not observed, or only minimally so, in the reperfused brain until 2 days after a 90 min of transient MCA occlusion. However, the lacZ expression dramatically increased at 7 days after the reperfusion, then diminished by 21 days. The majority of brain cells that expressed the lacZ gene were neurons and a fraction (5-10%) were astroglial cells. The present study showed that an exogenous gene was transferred and expressed in neural cells of ischemic and reperfused brains in vivo, but the temporal profile of the expression is dissociative.

Animals↗

Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease.

A possible protective effect of a novel free radical scavenger, OPC-14117, on the progressive motor neuron death in wobbler mice was examined. Clinical parameters such as mortality, body weight, motor activity as a rolling number of circular cage, and forelimb muscle power as grasping on a rolling column, an angle of slipping down from slope, and hanging ability on a flat plate were compared every 4 weeks from 4 to 36 weeks of age among mice groups treated with vehicle or daily oral administration of OPC-14117 of 10 or 30 mg/kg body weight. The treatment with OPC-14117 dose dependently improved the clinical parameters such as mortality, motor activity, and forelimb weakness. Pathological analysis showed that a diffuse neurogenic change in the forelimb muscle was improved at 36 weeks of age in the drug treated mice with a marked preservation of motor neurons in the spinal cord. Treatment of the mice with the drug reduced age-dependent increase of lipid peroxides in the spinal cord in vivo, and a supplement of the drug to the homogenate of spinal cord in vitro ameliorated the formations of lipid peroxides generated by an exogenous addition of ascorbate or xanthine/xanthine oxidase. These results suggest that OPC-14117 has a protective effect on the motor neuron death probably as a free radical scavenger, resulting in an improvement of clinical symptoms in wobbler mice.

Aldehydes↗

2.1 kb 5'-flanking region of the brain type dystrophin gene directs the expression of lacZ in the cerebral cortex, but not in the hippocampus.

Duchenne muscular dystrophy is a muscle-wasting disease accompanied by a variable, but often significant degree of mental retardation, possibly due to the absence of dystrophin. However, the function of brain type dystrophin remains insufficiently clear. With this background, in order to study the cell-specific regulation of brain type dystrophin expression in mice, we generated transgenic mice carrying the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene, fused to the coding region of the bacterial lacZ gene. Three transgenic mice lines showed lacZ expression in the cerebral cortex. However, lacZ expression was not detected in the CA region of the hippocampus. These results suggest that the 2.1 kb 5'-fragment of the mouse brain type dystrophin gene contains the regulatory element required for its expression in the cerebral cortex, but not in the hippocampus.

Animals↗

Potentiation by DSP-4 of EEG slowing and memory impairment in basal forebrain-lesioned rats.

The effects of cholinergic and noradrenergic depletion, alone and in combination, on spatial memory and electroencephalogram (EEG) activity were investigated. Basal forebrain-lesioned rats exhibited a significant decrease in cortical choline acetyltransferase activity and spatial memory impairment. In the cortical EEG, the basal forebrain lesion induced EEG slowing such as an increase in delta power activity and a decrease in beta power activity. Noradrenergic depletion following a treatment with DSP-4 (N-2-(chloroethyl)-N-ethyl-2-bromobenzylamine) had no effect on cortical choline acetyltransferase activity and spatial memory, but it aggravated the cognitive impairment induced by the basal forebrain lesion. DSP-4 itself increased delta power activity in non-lesioned rats, whereas DSP-4 potentiated the EEG slowing induced by the basal forebrain lesions. Systemic administration of tetrahydroaminoacridine at 1 or 3 mg/kg, i.p., ameliorated the memory deficits and EEG slowing induced by the basal forebrain lesion. However, the drug could not attenuate the EEG slowing and memory impairment in rats that had received a combination of DSP-4 and basal forebrain lesion. These results suggest that noradrenergic depletion aggravated the EEG slowing and the spatial memory impairment induced by cholinergic dysfunction and may decrease the efficacy of an anticholinesterase agent in reversing the cortical cholinergic hypofunction.

Animals↗

Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice.

We investigated both the effect and the mechanism of oral (p.o.) administration of PSK, a protein-bound polysaccharide derived from Basidiomycetes, on the anti-tumor T-cell response in gut-associated lymphoid tissue (GALT). The p.o. administration of PSK significantly suppressed the growth of colon 26 carcinoma (C-26) inoculated into the subserosal space of the cecum (i.c.), and augmented the tumor-neutralizing activity of the draining mesenteric lymph node (LN) cells. PSK treatment also significantly decreased the levels of immunosuppressive factors such as plasma transforming growth factor (TGF)-beta in the i.c. C-26-inoculated mice. We also evaluated the improving effect of PSK on the anti-tumor T-cell response in GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The PSK treatment promoted the rejection of i.c.-inoculated B7/P815 and restored the CD4+ T-cell-dependent proliferative response of the draining mesenteric LN cells against in vitro restimulation. Furthermore, the treatment also decreased the TGF-beta production but increased the IFN-gamma production of these cells. The p.o. administration of PSK, however, showed no effect in the CD8+ T-cell-dependent cytolytic activity of the draining mesenteric LN cells after in vitro restimulation. Overall, these results indicate that the p.o. administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in GALT, mainly through a suppression of TGF-beta production and a restoration of IFN-gamma production.

Administration, Oral↗

Primary structure and allergenic activity of trypsin inhibitors from the seeds of buckwheat (Fagopyrum esculentum Moench).

The complete amino acid sequences of two trypsin inhibitors BWI-2a and BWI-2b from the seeds of buckwheat (Fagopyrum esculentum Moench) were determined. BWI-2b consists of 51 amino acid residues containing two disulfide bonds. BWI-2a shares all amino acids with BWI-2b except for the C-terminal tripeptide: BWI-2a lacks Glu-Gly-Asn and ends with the Asp residue, making a total of 48 residues in the chain. The two disulfide bonds connect Cys11 to Cys32 and Cys15 to Cys28. BWI-2b shows no relatedness to the other buckwheat trypsin inhibitor reported [Belozersky et al. (1995) FEBS Lett. 371, 264-266]. Sequence comparison of BWI-2b with those of the other proteins included in PIR showed that BWI-2b is significantly homologous to the N-terminal region of storage proteins classified in the vicilin family. Furthermore, the allergenic activity of BWI-2b and the other buckwheat trypsin inhibitor BWI-1 was examined using the radioallergosorbent test. The result indicated that both inhibitors BWI-2b and BWI-1 have IgE binding activity, albeit to a low extent, suggesting that they might be minor allergenic proteins in buckwheat seeds.

Allergens↗

Ocular changes in patients with spinocerebellar degeneration and repeated trinucleotide expansion of spinocerebellar ataxia type 1 gene.

OBJECTIVE: To examine ocular changes in patients with spinocerebellar degeneration who have repeated trinucleotide expansion in the spinocerebellar ataxia type 1 (SCA1) gene. DESIGN: Ophthalmic findings in 6 patients from 3 families whose DNA analysis revealed that they had an expanded allele of the trinucleotide repeated in the SCA1 gene were compared with those of normal control subjects and other healthy family members. The DNA was extracted from peripheral blood lymphocytes of the neurodegenerative family and normal control subjects. SETTING: University medical center. RESULTS: Visual acuity gradually decreased in successive follow-up visits. Color vision and visual fields were gradually affected. Electroretinograms showed mild attenuation of oscillatory potentials. Corneal endothelial cell density was severely decreased from 600 to 1300 cells/mm2. These findings were not observed in the normal control subjects, other healthy family members, or other patients with spinocerebellar degeneration who had repeated trinucleotide expansion of other genes. CONCLUSION: To the best of our knowledge, this is the first report describing the association between ocular changes in patients with spinocerebellar degeneration and gene mutation. These ocular changes were considered specific to patients who had the expanded allele of the repeated trinucleotide in the SCA1 gene.

Adult↗

Microvessel count predicts metastasis and prognosis in patients with gastric cancer.

BACKGROUND AND OBJECTIVES: In order to evaluate the clinical relevance of angiogenesis in patients with gastric cancer, we investigated the microvessel count in gastric cancer tissues and compared the results with several clinicopathologic factors and prognosis. METHODS: A total of 55 patients with gastric cancer were included in this study. Microvessel count was determined by immunohistochemical staining using antifactor VIII-related antigen antibody. Histologically recognizable blood vessels within tissue sections served as internal control for immunostaining. Normal mouse IgG diluted to an equivalent protein concentration was used as a negative control in place of the primary antibody in each experiment. RESULT: The microvessel count ranged from 4.4 to 39.8 and the median count was 15.6. Microvessel count was significantly higher in patients with hepatic metastasis, lymph node metastasis, adjacent organ invasion, and lymphatic invasion. In patients who had undergone a curative operation, survival time in the hypervascular group was significantly shorter than that in the hypovascular group. CONCLUSIONS: Microvessel count correlated well with tumor progression and may serve as a useful prognostic factor in patients with gastric cancer.

Adult↗

Hard work does not result in a decrease in meal quality: the case of a Japanese farming village.

Historically, when Japanese farmers engaged in hard labor, they were likely to increase their carbohydrate intake without increasing intake of other nutrients. After Japan's economic growth started in the 1960s, however, many kinds of food became available and affordable. We investigated whether farmers today have increased the nutrients in their diet in proper proportion to energy expenditures when they are engaged in farming work by comparing the quantity and quality of meals between farmers and other villagers within a small area of a farming village. The quantity of energy and other nutrients increased with farming work, but the amounts of each nutrient per unit of energy did not decrease with the increase in energy intake. The intake of each nutrient relative to the recommended dietary allowance for energy and each nutrient did not decrease with farming work either. It was concluded that the quality of meals of farmers does not decrease with the increasing energy intake for farming work when many kinds of food are available and affordable.

Adult↗

FMLP actions and its binding sites in isolated human coronary arteries.

The chemoattractant f-Met-Leu-Phe (FMLP) can modulate human coronary arterial tone without the involvement of peripheral leukocytes. We investigated the actions of FMLP and its cellular mechanism in human coronary arteries isolated 2-3 h after death. A single dose of FMLP (0.01-10 microM) produced transient contraction (or, followed by relaxation) responses in most human coronary rings examined. These responses to FMLP were in large part mediated by the generation of cyclooxygenase products, mainly thromboxane A2 (TXA2) and prostaglandin I2 (PGI2). Radiolabeled N-formyl hexapeptide. 125I-f-Nle-Leu-Phe-Nle-Tyr-Lys bound densely to intimal and adventitial sites that accumulated macrophages (CD68-positive) with a Kd of 14-29 nM and, further, weakly to the media with a Kd of 2.4-3.6 microM. Several cell types including macrophages, endothelial cells and smooth muscle cells were positively immunostained for both TXA2 synthase and PGI2 synthase. However, there was no significant relation between the magnitude of the responses to FMLP and dense macrophage accumulation in the intimal plaques or the adventitia. A reverse transcription-polymerase chain reaction showed predominant expression of FMLP receptor homologues, FPRH1 and FPRH2 mRNA, in human coronary medial tissues relative to that in leukocytes. In conclusion. FMLP produced transient tension changes in human coronary arteries, mainly via the generation of TXA2 and PGI2. This effect of FMLP did not appear to be mediated by the activation of densely accumulated intimal and/or adventitial macrophages, but by the activation of unidentified medial tissue cells which might have functional FMLP receptor homologues.

Adolescent↗

Different enzyme activities in coronary capillary endothelial cells.

Differential distributions of alkaline phosphatase (AP) and dipeptydylpeptidase IV (DPPIV) were studied in coronary microvascular endothelial cells. Endothelial cells were obtained by the perfusion of coronary vessels with 0.1% trypsin PBS solution and cultured in uncoated culture dishes. Staining of cultured endothelial cells with AP- and DPPIV-sensitive reagents revealed blue or red staining, respectively. Most colonies showed cells of only one color, blue or red, even at the fifth passage. AP-sensitive cells, which were originally elongated, shortened and widened, proliferating to form monolayer colonies of cobble stone-like cells. AP-stainability became weak with repeated passages. DPPIV-sensitive endothelial cells remained elongated even after repeated passages. The cell shape and stainability seemed to be coupled and maintained through the five passages studied.

Alkaline Phosphatase↗

Immunological evaluation in oral lichen planus with chronic hepatitis C.

Oral lichen planus (OLP) is frequently associated with hepatitis C virus (HCV) infection. We have previously reported that the pathogenesis of OLP arises from host rather than viral factors. In this study, we investigated the role of these factors in 41 patients with chronic hepatitis C: 22 with OLP (group 1) and 19 without OLP (group 2). All patients had antibodies to HCV (anti-HCV) and were serum HCV RNA-positive; none were HBsAg-positive. Immune abnormalities in serum were evaluated by testing for antinuclear antibody (ANA), rheumatoid factor (RF) activity, immunoglobulins (IgG, IgM, and IgA), and cryoglobulin. The rate for ANA positivity and IgM levels were significantly higher in group 1 than in group 2 (P < 0.05). Mean age in group 1 was significantly higher in group 2 (P = 0.0001). Of the factors tested, ANA, IgM, and age, logistic regression showed that age correlated independently with OLP (P = 0.003). In 5 patients in group 1, the infiltrating lymphocytic subsets of the OLP lesion were examined histopathologically. Predominant T cell infiltration was shown in all 5 patients. In addition to host factors, wer also examined viral factors in both groups of patients, measuring serum HCV RNA level and determining HCV genotype. There were no significant differences between the groups in these viral factors. This study suggested that host factors induced by the HCV infection are more important than viral factors in the pathogenesis of OLP associated with hepatitis C.

Chronic Disease↗