Biomedical subjects

S Haga

Publications and source records attributed to S Haga.

At least 91 records · Page 5Linked to original sources

PubMed1997

Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress.

Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1+ FcgammaRII/IIIbright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1+ FcgammaRII/IIIbright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5 degrees C. We next investigated the effects of improved cold tolerance on the generation of MAC-1+ FcgammaRII/IIIbright cells during acute cold stress. Mice were adapted to cold by exposure to 5 degrees C for 3 wk (cold-acclimated mice) and then reexposed to 5 degrees C for 3 h (acute cold stress) after living at 25 degrees C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.

Acclimatization↗

PubMed1997

Effect of swimming training on antioxidant enzymes in kidney of young and old mice.

The current study was undertaken to investigate the effect of swimming training on the antioxidant enzyme system in kidney of young and old mice. Both young and old mice, aged 2 and 26 months old, respectively, were divided into the sedentary and swimming-trained groups. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in water at 35-36 degrees C. Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity was significantly decreased with aging but was not influenced by swimming training, such changes being similar to those noted for catalase activity rather than for glutathione peroxidase activity. After swimming training Mn-SOD activity increased significantly only in old mice but was unaffected by aging. Although neither aging nor swimming training had overt effect on the expression of Cu,Zn-SOD mRNA, the immunoreactive Cu,Zn-SOD content in young mice decreased significantly after the training. Meanwhile, Mn-SOD mRNA expression in old mice was reduced by half after swimming training, accompanied by a significant decrease in its immunoreactive content; unexpectedly, however, Mn-SOD content in young mice did not parallel its mRNA expression. These findings suggest that the antioxidant enzyme system in mouse kidney trends to be down-regulated with aging, and that swimming training fails to attenuate such reduced levels of the antioxidant enzymes.

Aging↗

PubMed1997

[Blood biochemical properties in male workers analysed according to body type].

The characteristics of body type, serum lipids and blood pressure in male blue workers were evaluated. The subjects were 1,705 healthy men aged 40.3 +/- 4.33 years, and were classified into 4 groups according to body mass index: BMI; lean (group L: BMI < 20), normal (group N: 20 < or = BMI < 24), mildly obese (group MO: BMI 24 to 26.5) and obese group (group O: BMI > 26.5). The physical characteristics, blood pressure and 14 blood constituent items were measured. Groups L, N, MO and O accounted for 8.5, 53.4, 28.6, and 9.4% of all subjects, that is the obese body type (MO and O groups) occupied 38%. Rest systolic and diastolic blood pressure were positively related to BMI. Most blood constituent items biochemically analyzed increased in proportion to BMI values. The Trigriceride level was 88.5, 112.2, 152.8 and 171.9 mg/dl in groups L, N, MO and O, respectively. The Trigriceride level in groups MO and O were about the upper limit of the normal range. The total cholesterol level was in the normal range in 4 groups, but was higher in the MO and O groups than in groups L and N. The HDL-cholesterol level was low in inverse proportion to BMI, that is 58.2, 51.3, 47.6, and 42.6 mg/dl in groups L, N, MO, and O, respectively. Especially the values in group O were similar to the values in the aged and adult disease patients. A greater percentage of Japanese male workers were obese men and they risked developing atherosclerosis and adult diseases. the present study suggests that health education regarding exercise prescription and nutrition intake in daily life should be provided.

Adult↗

PubMed1996

Accumulation of apolipoprotein E and beta-amyloid-like protein in a trace of the hippocampal CA1 pyramidal cell layer after ischaemic delayed neuronal death.

We found that apolipoprotein E (apo E) accumulates in a trace of the hippocampal CA1 pyramidal cell layer within 6 months after 5 min ischaemia. Intense methenamine-silver (M-S) stainings were seen in the entire CA1 subfield 3 months after ischaemia. The M-S staining pattern may imply the appearance of soluble A beta-like proteins. The apo E-positive trace was also positively stained with anti-beta-amyloid (A beta) protein antibodies, but not with anti-beta-amyloid protein precursor (APP) antibodies. These results suggest that A beta-like protein accumulates in ischaemic brain after neuronal cell death. Adjacent reactive astrocytes showed both apo E- and A beta-immunoreactivities. These astrocytes may be involved in the clearance of apo E- and A beta-positive material. We presume that the coincident distribution pattern for apo E- and A beta-immunoreactivity implies formation of the insoluble and stable A beta-apo E complex which is known to exist in the brain of individuals with Alzheimer's disease. The ischaemic model may be useful in studying apo E and A beta deposition in the brain.

Amyloid beta-Peptides↗

PubMed1996

Complement gene expression in mouse microglia and astrocytes in culture: comparisons with mouse peritoneal macrophages.

We investigated the mRNA expression of the various complement components in cultured mouse microglia and astrocytes by the reverse transcription and polymerase chain reaction. C1q, C2, C3, and C4 mRNAs were detected in microglial cultures. C3 and C4 mRNAs were found in astrocyte cultures. Microglia showed enhanced expression of C2, C3, and C4 mRNAs when they were treated with lipopolysaccharide. Much higher expression of C1q, C2, C3, and C4 mRNAs was detected in microglia after stimulation with interferon-gamma. Our data suggest that microglia and astrocytes may produce some of the complement components also in vivo, which can be facilitated in certain infectious and inflammatory diseases in the central nervous system.

Animals↗

PubMed1996

Swimming training improves brown-adipose-tissue activity in young and old mice.

The impairment of brown adipose tissue (BAT) thermogenic activity with aging has been well documented. The current study investigated the effect of swimming training on BAT activity in 2-month-old (young) and 26-month-old (old) male mice. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in water at 35-36 degrees C. Compared with young sedentary mice, the BAT-to-body mass ratio was markedly smaller in old sedentary mice, accompanied by the decreased amount of protein, whereas there was no significant difference in uncoupling protein (UCP) content, UCP mRNA expression, or guanosine 5'-diphosphate (GDP) binding (an index of UCP activity) between young and old mice. Meanwhile, the swimming training definitely increased BAT mass and its protein content in both the young and old mice, suggesting hypertrophy and hyperplasia. In addition, after the swimming training, the amounts of protein, UCP antigen, and GDP binding in the mitochondria recovered from BAT of both mice increased significantly as compared with the respective sedentary groups, while the expression of UCP mRNA did not vary substantially. These findings suggest that, irrespective of age, swimming training enhances the thermogenic activity and capacity in BAT of mice.

Adipose Tissue, Brown↗

PubMed1996

Relation between Locoregional Hyperthermic Area Detected by Contact Thermography and the Maximum Density of Tumor Stain Obtained by IV-DSA in Breast Cancer Patients.

We studied the significance of the locoregional hyperthermic area observed by contact thermography in relation to the maximum density of tumor enhancement obtained by IV-DSA. The subjects were 34 patients with primary breast cancer. The thermal difference between the locoregional hyperthermic area and the surrounding mammary tissues was obtained, and the maximum density of tumor stain on IV-DSA was calculated from the time-density curve. Twenty-three (67.6%) patients had a locoregional hyperthermic area corresponding to the tumor. The higher the degree of thermal difference between the hyperthermic area and the surrounding tissues, the higher the maximum density of tumor enhancement. As the maximum density of tumor stain is considered to reflect the vascularity of the tumor, the degee of the locoregional hyperthermic area obtained by thermography may also reflect tumor vascularity.

Journal Article↗

PubMed1996

Effects of aging and/or training on antioxidant enzyme system in diaphragm of mice.

We investigated the effects of aging and/or swimming training on the antioxidant enzyme system in diaphragm of mice. Young (2 months old) and old (26 months old) male mice were swimming-trained for 6 weeks (1 h/day, 5 days/week). Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) activity was significantly upregulated with aging, and swimming training definitely enhanced the activity only in young mice. Neither aging nor swimming training had overt effect on Mn-SOD activity. Glutathione peroxidase activity in young mice was significantly increased after training, but not in old mice. Both of immunoreactive Cu,Zn-SOD and Mn-SOD were significantly increased with aging but were unaffected by swimming training. Consequently, physical training significantly enhanced the specific activity of Cu,Zn-SOD in young mice, but not in old mice. Meanwhile, swimming training significantly increased xanthine oxidase activity in both age groups, the extent of the increase being greater in old mice than in young mice. We concluded that the antioxidant enzyme system in mouse diaphragm trends to be upregulated with aging, but that swimming training improved the system only in young mouse diaphragm.

Aging↗

PubMed1996

Multicentric pleomorphic xanthoastrocytomas: case report.

We report the case of a 22-year-old woman who developed multicentric pleomorphic xanthoastrocytomas (PXAs) in the cerebral hemisphere. She underwent a first operation for a PXA in the right parietal lobe at the age of 7 years and a second operation at the age of 15 years in the right frontal lobe, remote from the previous tumor site. At age 22 years, she was found to have a tumor, which was a newly formed PXA, in the left occipital lobe. There was no recurrent tumor in the right frontal lobe. Clinical and pathological aspects of multicentric PXAs are reviewed and discussed.

Adolescent↗

PubMed1996

Effective isolation of MPB64 from a large volume of culture filtrate of Mycobacterium bovis BCG Tokyo.

MPB64, a secretory protein of Mycobacterium bovis BCG Tokyo, was isolated from a culture filtrate of the bacteria in Sauton synthetic medium harvested on day 8. The protein was isolated by five steps; (i) concentration of the culture filtrate by cutting the molecules smaller than 5 kDa with the Millipore Pellicon Cassette system, (ii) affinity separation by a Phenyl Sepharose CL-4B column, (iii) separation with a DEAE-Sepharose CL-6B column with 3 M urea, (iv) separation with a Sephacryl S200HR column, and (v) separation with a DEAE-Sepharose column without urea. MPB64 in each fraction was determined by comparing the band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with that of standard MPB64. The specificity of isolated MPB64 was tested by immunoblotting with anti-MPB64 antibody. The potency of isolated MPB64 in eliciting skin reaction in the BCG-sensitized guinea pigs was the same to that of standard MPB64. The method described herein is an improved one for isolating MPB64 from a large volume of culture filtrate of M. bovis BCG Tokyo. The technique should be applicable to isolation of other mycobacterial secretory proteins.

Antigens, Bacterial↗

PubMed1996

[Detection of rifampicin-resistant strains of Mycobacterium tuberculosis by a non-radioactive PCR-SSCP method].

PCR-SSCP method to detect genetic mutations in rpoB gene as a marker of rifampicin-resistance was developed by Telenti et al., and we have modified it applying non-radioactive PhastSystem for more practical use in the detection of rifampicin-resistance of Mycobacterium tuberculosis. PCR products amplified with the primers specific to rpoB gene using extracted DNA from 89 strains of M. tuberculosis were sequenced and the amino acid sequences were morphism was determined by the PhastSystem. The bands were stained by silver staining. Among 89 strains of M. tuberculosis, 43 were confirmed as rifampicin-resistant (RFPr) and 46 were rifampicin-sensitive (RFPs) by the culture on the drug-containing media. All of the 43 RFPr strains had one or more mutations in the DNA sequence of rpoB gene, while none of the RFPs strains had such mutations. However, by PCR-SSCP, only 20 out of 43 RFPr strains showed clear differences in the band pattern of electrophoresis from that of RFPs strains. Other 23 RFPr strains had only slight differences in the band pattern of the PCR-SSCP from that of RFPs strains. But it was noticed that the main bands of RFPr strains were distinguishable from the main bands of RFPs strains even their patterns were similar. Thus, it is possible to apply a non-radioactive PCR-SSCP for the detection of rifampicin resistance of M. tuberculosis with further improvement of the condition of gel electrophoresis or staining techniques.

Amino Acid Sequence↗

PubMed1996

Localization of binding sites of Ulex europaeus I, Helix pomatia and Griffonia simplicifolia I-B4 lectins and analysis of their backbone structures by several glycosidases and poly-N-acetyllactosamine-specific lectins in human breast carcinomas.

Several studies have shown the deletion of blood group A or B antigens and the accumulation of H antigens in human breast carcinomas. Other studies have independently demonstrated that the binding sites of lectins such as Helix pomatia agglutinin (HPA) and Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) are highly expressed in these cells. In order to clarify the molecular mechanisms of malignant transformation and metastasis of carcinoma cells, it is important to understand the relationship between such phenotypically distinct events. For this purpose, we examined whether the binding sites of these lectins and Ulex europaeus agglutinin I (UEA-I) are expressed concomitantly in the same carcinoma cells and analyzed their backbone structures. The expression of the binding sites of these lectins was observed independently of the blood group (ABO) of the patients and was not affected by the histological type of the carcinomas. Observation of serial sections stained with these lectins revealed that the distribution of HPA binding sites was almost identical to that of GSAI-B4 in most cases. Furthermore, in some cases, UEA-I binding patterns were similar to those of HPA and GSAI-B4 but in other cases, mosaic staining patterns with these lectins were also observed, i.e., some cell clusters were stained with both HPA and GSAI-B4 but not with UEA-I and adjacent cell clusters were stained only with UEA-I. Digestion with endo-beta-galactosidase or N-glycosidase F markedly reduced the staining intensity of these lectins. Together with the reduction of staining by these lectins, reactivity with Griffonia simplicifolia agglutinin II appeared in carcinoma cells following endo-beta-galactosidase digestion. Among the lectins specific to poly-N-acetyllactosamine, Lycopersicon esculentum agglutinin (LEA) most vividly and consistently stained the cancer cells. Next to LEA, pokeweed mitogen agglutinin was also effective in staining these cells. Carcinoma cells reactive with these lectins corresponded well to those stained with both HPA and GSAI-B4, and in some cases, with UEA-I. These results demonstrate that the binding sites of UEA-I, HPA, and GSAI-B4 are expressed concomitantly in the same carcinoma cells and all carry linear and branched poly-N-acetyllactosamine on N-glycans, suggesting that the synthesis of this complex carbohydrate is one of the most important and basic processes leading to the malignant transformation of cells, invasion, and metastasis of carcinoma cells.

ABO Blood-Group System↗

PubMed1995

Protective immune responses induced by secretion of a chimeric soluble protein from a recombinant Mycobacterium bovis bacillus Calmette-Guérin vector candidate vaccine for human immunodeficiency virus type 1 in small animals.

A recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) vector-based vaccine that secretes the V3 principal neutralizing epitope of human immunodeficiency virus (HIV) could induce immune response to the epitope and prevent the viral infection. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein and established the principal neutralizing determinant (PND)-peptide secretion system in BCG. The recombinant BCG (rBCG)-inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide, followed by passive transfer of the DTH by the systemic route. Further, immunization of mice with the rBCG resulted in induction of cytotoxic T lymphocytes. The guinea pig immune antisera showed elevated titers to the PND peptide and neutralized HIVMN, and administration of serum IgG from the vaccinated guinea pigs was effective in completely blocking the HIV infection in thymus/liver transplanted severe combined immunodeficiency (SCID)/hu or SCID/PBL mice. In addition, the immune serum IgG was shown to neutralize primary field isolates of HIV that match the neutralizing sequence motif by a peripheral blood mononuclear cell-based virus neutralization assay. The data support the idea that the antigen-secreting rBCG system can be used as a tool for development of HIV vaccines.

AIDS Vaccines↗

PubMed1995

Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes and mapping of Rapop1, a novel susceptibility gene.

Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes was performed by counting dead cells in histologically processed thymuses after 0.5 Gy of whole-body X-irradiation, using recombinant congenic (CcS/Dem) strains derived from inbred mouse strains BALB/cHeA (susceptible) and STS/A (resistant). A high (8/20) number of strains with lower dead cell scores than BALB/cHeA among CcS/Dem recombinant congenic strains (RCS), which contain 12.5% of STS/A genome in the genetic background of BALB/cHeA strain, indicates that the difference between BALB/cHeA and STS/A is caused by several genes and that susceptibility probably requires BALB/cHeA alleles at more than one locus. Similar results were obtained with CXS/Hg recombinant inbred (CXS/Hg) strains. Analysis of F2 hybrids between BALB/cHeA and CcS-7, one of the CcS/Dem strains that showed lower dead cell scores than BALB/cHeA, demonstrated that a novel gene (Rapop1, radiation-induced apoptosis 1) controlling susceptibility to radiation-induced apoptosis in the thymus is located in the proximal region of mouse chromosome 16.

Animals↗

PubMed1995

Delayed-type hypersensitivity to a recombinant mycobacterial antigen, MPB64, in guinea pigs sensitized to Mycobacterium tuberculosis or Mycobacterium bovis BCG.

Recombinant MPB64 (rMPB64), a mycobacterial antigen, was obtained from an Escherichia coli clone transformed with a recombinant expression vector, pMAL64c. The rMPB64 was examined for the activity to elicit delayed-type hypersensitivity (DTH) in guinea pigs injected with liver Mycobacterium tuberculosis H37Rv or live M. bovis BCG Tokyo. It was found that rMPB64 has the same reactivity as native MPB64 (nMPB64) or MPT64 (nMPT64) and the potency to elicit DTH was 13.4 times higher than that of PPD. Because MPB64 is secreted only by living M. tuberculosis and some strains of BCG, it is possible to use this antigen for the diagnosis of tuberculosis.

Amino Acid Sequence↗

PubMed1995

Histopathological study of local residual carcinoma after simulated lumpectomy.

From 1989 to 1991, 24 patients with invasive ductal carcinoma underwent simulated lumpectomy at Tokyo Women's Medical College Daini Hospital. The mastectomy specimens were then examined histopathologically in serial sections for the presence of residual tumors or multicentricity. Lumpectomy specimens from cancer foci at resected margins were also examined. In this study, 23 of 24 patients demonstrated positive resection margins (95.8%). Residual tumors were found in mastectomy specimens from 16 patients (66.7%); unilateral multifocal carcinomas were found in 2 of these patients (8.3%). The incidence and severity of residual tumors did not correlate with primary tumor size or the distance between the nipple and the primary tumor but directly correlated with the severity of intraductal spread of the primary tumor. Tumors with central necrosis were associated with a higher incidence of residual tumors. Our study thus indicates that there is a high risk that some residual tumor will be left in the conserved breast when lumpectomy is performed. Multifocal carcinoma and tumors showing severe intraductal spread and central necrosis are thus associated with extensive residual tumors and are likely to cause local recurrence.

Breast Neoplasms↗

PubMed1995

Relationship between staining by digital subtraction angiography and vascularity in breast cancer: analysis of the time-density curve and the results of staining for factor VIII-related antigen/von Willebrand factor.

We performed intravenous digital subtraction angiography (IV-DSA) in 31 patients with primary invasive breast cancer, and calculated the maximum density of tumor staining from the time-density curve obtained. Specimens resected from the same patients were stained for factor VIII-related antigen/von Willebrand factor (vWF), and the amount of microvessels was calculated by image processing. A significant correlation (correlation coefficient: 0.85) was found between the maximum density of tumor staining and the vascularity determined by staining for vWF, indicating that the maximum density indirectly reflects the vascularity in the tumor.

Angiography, Digital Subtraction↗

PubMed1995

Homology between the MPB70 and MPB83 proteins of Mycobacterium bovis BCG.

Isolation of MPB83 from Mycobacterium bovis BCG Tokyo culture fluid is described. MPB70 and MPB83 have similar molecular mass as judged by SDS-PAGE but differ in isoelectric points. Peptides isolated after CNBr cleavage of MPB83 revealed extensive homology as well as distinct differences from corresponding parts of the amino acid sequence deduced from the mpb70 gene cloned by Terasaka et al. Antibodies produced by immunization with MPB70 and MPB83 had distinctly different fine specificity revealing cross-reactivity between the proteins. These findings indicate that two distinct, homologous genes code for these proteins. Sensitization with live BCG Tokyo also induced T cell responses to MPB83 with development of delayed type hypersensitivity in guinea pigs.

Amino Acid Sequence↗