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Biomedical subjects

S Haga

Publications and source records attributed to S Haga.

197 records · Page 11Linked to original sources
PubMed1976

Immuno-electron microscopic localization of immunoglobulins in amyloid fibrils of senile plaques.

Amyloid fibrils in senile plaques of the brain of patients with senile dementia or Alzheimer's disease combined specifically with horseradish peroxidase (HRPO)-labeled rabbit anti-human IgG. Light and electronmicroscopic immunoperoxidase technique was used to prove this. The fact may mean that immunological factors were involved in the pathogenesis of amyloid fibrils in the senile plaques, and probably also in that of senile dementia or Alzheimer's disease.

Alzheimer Disease↗
PubMed1975

Identification of components of immunoglobulins in senile plaques by means of fluorescent antibody technique.

Using a fluorescent antibody technique, sections of the brains of patients with senile dementia or Alzheimer's disease containing senile plaques were treated with rabbit antihuman immunoglobulins labelled with FITC (fluorescein isothiocyanate, BBL). The senile plaques and the cerebral amyloid angiopathy (drusige Entartung, Scholz, 1938) in the brains of patients with senile dementia or Alzheimer's disease showed specific fluorescence. Control sections from the brains of a girl who died from carcinoma of the stomach and of a female schizophrenic who died from lung abscess, showed only slight fluorescence in a few vessel walls. The presence of components or fragments of immunoglobulins in a senile plaques may mean that immunological factors are involved in their pathogenesis and probably also in that of senile dementia and Alzheimer's disease.

Aged↗
PubMedDate not supplied

Strenuous endurance training in humans reduces oxidative stress following exhausting exercise.

The aim of this study was to evaluate whether high-intensity endurance training would alleviate exercise-induced oxidative stress. Nine untrained male subjects (aged 19-21 years) participated in a 12-week training programme, and performed an acute period of exhausting exercise on a cycle ergometer before and after training. The training programme consisted of running at 80% maximal exercise heart rate for 60 min.day-1, 5 days.week-1 for 12 weeks. Blood samples were collected at rest and immediately after exhausting exercise for measurements of indices of oxidative stress, and antioxidant enzyme activities [superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT)] in the erythrocytes. Maximal oxygen uptake (VO2max) increased significantly (P < 0.001) after training, indicating an improvement in aerobic capacity. A period of exhausting exercise caused an increase (P < 0.01) in the ability to produce neutrophil superoxide anion (O2.-) both before and after endurance training, but the magnitude of the increase was smaller after training (P < 0.05). There was a significant increase in lipid peroxidation in the erythrocyte membrane, but not in oxidative protein, after exhausting exercise, however training attenuated this effect. At rest, SOD and GPX activities were increased after training. However, there was no evidence that exhausting exercise enhanced the levels of any antioxidant enzyme activity. The CAT activity was unchanged either by training or by exhausting exercise. These results indicate that high-intensity endurance training can elevate antioxidant enzyme activities in erythrocytes, and decrease neutrophil O2.- production in response to exhausting exercise. Furthermore, this up-regulation in antioxidant defences was accompanied by a reduction in exercise-induced lipid peroxidation in erythrocyte membrane.

Adult↗
PubMedDate not supplied

A monoclonal antibody to amyloid in the brains of patients with Alzheimer's disease.

A monoclonal antibody that reacts with the amyloid in senile plaques in the brains of patients with Alzheimer's disease, was produced. The antigen was the crude amyloid protein (DAM, Pras et al. 1968) from the spleen of a patient with primary amyloidosis. The antibody crossreacts with DAM, but does not stain the amyloid of primary amyloidosis in tissue sections. The presence of a common antigenic site or sites in both the amyloid of senile plaques and amyloid of primary amyloidosis which react with this antibody is postulated.

Aged↗
PubMedDate not supplied

The immunohistochemical demonstration of subsequences of the precursor of the amyloid A4 protein in senile plaques in Alzheimer's disease.

The actual presence of the predicted precursor of Alzheimer's disease amyloid A4 protein, reported by Kang et al. (1987) in the Alzheimer brain, has yet to be verified. To identify the various regions of this precursor, antibodies were raised against three synthetic polypeptides, R35 (residues 274-286), R36 (residues 527-540), and R37 (residues 681-695), subsequences of the precursor protein; the specificity of these antibodies was ascertained by ELISA. Upon immunohistochemical examination, the antibody to R35 failed to react, but the antibody to R36 (the extracellular part) stained the amyloid of senile plaques and the staining pattern was identical to that of anti-A4 antibody. The antibody to R37 (the C-terminal intracellular part) stained what may be degenerating neurites in senile plaques whereas the amyloid remained unstained. An anti-neurofilament (NF) antibody reacted with some of the R37-positive grains, but R37-negative grains also were seen. Further, some R37-positive grains were not stained by the anti-NF antibody. The anti-GFAP antibody and the anti-macrophage antibody did not stain the R37-positive grains. These findings indicate that the amyloid protein in senile plaques actually contains a larger polypeptide than the A4 protein, and suggest that the intracellular C-terminal part of the precursor may exist in the degenerated neurites seen in senile plaques.

Aged↗
PubMedDate not supplied

Muscle type-specific response of PGC-1 alpha and oxidative enzymes during voluntary wheel running in mouse skeletal muscle.

AIM: It is generally accepted that endurance exercise increases the expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), which governs the expression of oxidative metabolic enzymes. A previous report demonstrated that the regulation of mitochondrial protein expression in skeletal muscles in response to cold exposure depends on muscle fibre type. Cold exposure and endurance exercise are both metabolic challenges that require adjustments in mitochondrial energy metabolism, we hypothesized that the exercise-induced increase in oxidative enzymes and PGC-1alpha expression is higher in fast-type than in slow-type muscle. METHODS: Female ICR mice were individually housed in cages equipped with running wheel for 1, 2, 4, 6 or 8 weeks. The soleus, plantaris (PLA) and tibialis anterior (TA) muscles were then prepared from each mouse. The expression levels of PGC-1alpha, mitochondrial proteins and GLUT4 were evaluated by Western blotting. RESULTS: The expression level of PGC-1alpha was increased only in the PLA muscle. Furthermore, the expression levels of all mitochondrial proteins and GLUT4 in the PLA muscle were increased. In the TA muscle, although there was no increase in PGC-1alpha expression, the expression levels of mitochondrial proteins and GLUT4 were increased. CONCLUSIONS: These results suggest that muscle type-specific responses occur during endurance exercise, and that the increase in PGC-1alpha expression is not the only factor that promotes oxidative capacity as a result of endurance exercise.

Animals↗
PubMedDate not supplied

Overexpression of the p53 gene product in canine mammary tumors.

p53, a tumor suppressor gene, is a target of genetic alternations in many human and animal cancers. Compared to normal tissues, cancer tissues overexpress mutant p53 protein thus allowing their detection by a number of immunochemical procedures. To what extent the expression of mutant p53 correlates with dog mammary tumorigenesis has not been fully studied. In the present study, 20 spontaneously arising canine mammary tumors were examined for overexpression of mutant p53. Two different monoclonal antibodies, BP53-12 and PAb122, which recognize different epitopes of the p53 product, were used. The canine tumors in the present study exhibited five different histological types: i) osteosarcoma (n=7); ii) carcinosarcoma (n=4); iii) solid carcinoma (n=5); iv) complex carcinoma (n=3); and v) tubulopapillar carcinoma (n=1). The positive ratios against BP53-12 and PAb122 antibodies were 50% (10/20) and 60% (12/20) respectively. Among these positive samples, 35% (7/20) reacted to both antibodies. Finally, 15 out of 20 tumors showed positivity against one of the monoclonal antibodies. Mostly, as in human mammary tumor cells, BP53-12 staining was observed in the nuclei of tumor cells. PAb122 staining, however, was confined to cytoplasm of osteosarcoma or carcinosarcoma cells. To confirm the location of the staining, immunoelectron microscopy was done. The results showed that the cytoplasm of cartilage cells in the sarcomas had positive staining. These results indicate that anti-p53 antibodies BP53-12 and PAb122, generated against human p53 are cross reacting with the same molecule in canine cells and that the role of p53 in tumorigenesis is not only confined to tumors in human. Our finding suggests that a combination of p53 monoclonal antibodies should be used to screen, not only canine mammary tumors but also human mammary tumors, to obtain a better tumor prognosis.

Adenocarcinoma↗
PubMedDate not supplied

Antitumor efficacy of combination chemotherapy with UFT and cyclophosphamide against human breast cancer xenografts in nude mice.

The combination of cyclophosphamide (CPA) and 5-fluorouracil (5-FU) is currently regarded as the most effective therapy for the treatment of patients with advanced and recurrent breast cancer. We evaluated the augmentation of antitumor activity and toxicity by coadministration of CPA and UFT (1M tegafur--4M uracil) instead of intravenous 5-FU on H-31 human breast cancer xenografts in nude mice. The maximum tolerable dose (MTD) of UFT alone (24 mg/kg) and CPA alone (85 mg/kg) had a significant effect on H-31 tumors in mice with 86.6% and 83.0% inhibition rates of tumor growth, respectively, and without loss of body weight, diarrhea or myelosuppression. The combined administration with full and 83.3% MTD of UFT and CPA augmented the antitumor activity compared to that of UFT alone and CPA alone. The relative tumor volume of the UFT plus CPA-treated group to the UFT- and CPA-treated groups was 0.28 and 0.36 for the full MTD, and 0.51 and 0.67 for 83.3% MTD, respectively. When CPA was consecutively administered to the tumor-bearing mice for 14 days, there were no decreases in the activities of enzymes related to 5-FU metabolism, but there was an significant increase in the activity of ribonucleotide reductase, suggesting that anabolism of 5-FU derived from tegafur is accelerated to some extent by coadministration of CPA. In conclusion, these results suggest that combination therapy with oral UFT and CPA may be useful for the long-term treatment of cancer patients with advanced and recurrent breast cancers.

Animals↗
PubMedDate not supplied

Determining the telomerase activity of exfoliated cells in intestinal lavage solution to detect colorectal carcinoma.

In order to make a definitive diagnosis of colorectal carcinoma, it is desirable to detect cancerous cells in stool samples. The detection of cancer gene products in stool samples, however, is said to be extremely difficult. The involvement of telomerase in the development of various malignancies has been reported. We therefore performed colonoscopy and thereby collected the intestinal lavage solution remaining in the lower portion of rectum to determine any possible signs of colorectal carcinoma. This fluid consisted of a combination of stool and exfoliated intestinal mucosa. We examined the telomerase activity of the intestinal lavage solution, collected from 19 colorectal carcinoma patients and from 11 volunteers (colonospically normal controls) based on the method of the telomeric repeat amplification protocol (TRAP) assay. All patients drank a polyethylene glycol-electrolyte lavage solution (PEG-ELS) before the examination. Sample solutions were collected by the colonoscope at the beginning of colonoscopy. Telomerase activity was thus found in 11 (57.9%) of the 19 intestinal lavage solution samples. In contrast, all eleven samples from the colonoscopically normal subjects were negative. These findings thus suggest that measuring telomerase activity of exfoliated cells in intestinal lavage solution may thus be useful as a new diagnostic method for colorectal carcinoma.

Aged↗
PubMedDate not supplied

Intrahepatic lymphocyte analyses and assessment of the effects of levamisole in murine hepatic metastasis model.

We used hepatic metastasis models to determine the mechanism and effect of levamisole. BALB/c mice and Colon 26 cells were used. Group I was injected with tumor cells through the portal vein. Group II was primed with tumor cells before tumor cells injecting. Group III was same as Group II, but treated with levamisole. Surface antigens of intrahepatic lymphocytes and spleen cells were determined by FACScan with Anti-CD3, anti-CD4, anti-CD8, anti-CD45, anti-NK1.1 and anti-F4/80. Nodules on the liver were greatest in Group I and fewest in Group III. Concerning intrahepatic lymphocytes, Group II, when compared with Group I, had increases of CD3+, CD4+ and CD8+ cells, and decreases of CD45+ and NK1.1+ cells. Group III when compared with Group II, showed increased CD8+ cells and decreased of NK1.1+ cells. Levamisole is considered to be effective in the prevention of liver metastasis and is suggeste to enhanced CD8+ cells.

Adjuvants, Immunologic↗