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Biomedical subjects

T Kagawa

Publications and source records attributed to T Kagawa.

At least 91 records · Page 5Linked to original sources
PubMed1992

A morphological and ultrastructural investigation of normal mouse brain tissue after intracerebral injection of tumor necrosis factor.

Morphological and ultrastructural changes in normal mouse brain tissue were investigated after intracerebral stereotactic injections of tumor necrosis factor (specific activity: 2.0 x 10(6) U/mg protein) into the right frontal lobe. The mice received either a single infusion or multiple tumor necrosis factor infusions in three different dose groups (10, 100, or 500 U). Compared with sham-treated control mice that received adjusted intracerebral injections of purified albumin, the tumor necrosis factor-treated mice in all dose groups did not show any specific in vivo behavioral abnormalities during the 2 months of study following the infusions. Histological studies revealed hemorrhage attributable to the mechanics of the intracerebral infusions, a thickening of the arachnoid membranes, a reactive gliosis, and neutrophilic and/or mononuclear cell infiltration along the infusion pathway. A local neutrophilic response was prominent 1 day after tumor necrosis factor injection. An immunohistochemical analysis indicated that the mononuclear cell infiltration consisted of lymphocytes and macrophages. Except for the transient neutrophilic infiltration, these histological alterations did not differ from those seen in the sham-treated control groups, and most nonspecific reactive changes disappeared within 8 weeks after the injections. Furthermore, an ultrastructural study showed no apparent pathological changes in the cytoplasmic organelles of neuronal, glial, and endothelial cells in the tumor necrosis factor-injected mouse specimens. These results suggest that the tumor necrosis factor injections caused no specific toxicity and did not alter the parenchymal and stromal cells comprising normal mouse brain tissue.

Animals↗
PubMed1992

Effect of dexamethasone, dimethylsulfoxide and sodium butyrate on a human hepatoma cell line PLC/PRF/5.

The effects of agents which are known to be differentiation inducers on a human hepatoma cell line PLC/PRF/5 were investigated. Dexamethasone (DEX), sodium butyrate (SB) or dimethylsulfoxide (DMSO) were examined. They all reduced cell proliferation but differ from each other in effect on the secretion of alphafetoprotein (AFP) and hepatitis B surface antigen (HBsAg), changes in morphology and RNA transcription. SB changed the cell from polygonal into a fibroblast-like type and decreased AFP secretion. DMSO decreased the cell size and changed AFP secretion in the same manner as SB. DEX changed the cell into a larger size, as well as increased AFP secretion. HBsAg secretion and also HB virus DNA transcription was enhanced by 3 agents. AFP and myc gene transcriptions were reduced by SB but DMSO reduced only AFP. Albumin gene transcription was enhanced by SB and DEX. These results indicate that the decrease of PLC/PRF/5 proliferation is induced through different mechanisms by these 3 agents.

Butyrates↗
PubMed1992

Comparative study of cerebral protection during surgery of thoracic aortic aneurysm.

During the past 5 years, 30 cases of thoracic aortic aneurysm were treated. Selective cerebral perfusion (SCP) and retrograde cerebral perfusion (RCP) were conducted for cerebral protection during aortic cross clamping. SCP was carried out in 5 cases of dissecting aneurysm (all Stanford type A, including a case of AAE) and 3 cases of arch aneurysm. RCP was conducted in 5 cases of dissecting aneurysm (4 Stanford type A, 1 Stanford type B with retrograde dissection) and 2 cases of aortic arch aneurysm. The mean cerebral perfusion time of SCP exceeded that of RCP (89 +/- 26 min in SCP versus 61 +/- 33 min in RCP p < 0.05). The hospital mortality rate was 38% (SCP) and 29% (RCP). Neurological complications were prolonged unconsciousness (1/8 in SCP, 1/7 in RCP) and transient paralysis (0/8 in SCP, 1/7 in RCP). Although the mechanism for the cerebral protective effect of RCP is unknown, this perfusion method is easy and safe, requiring little time for ascending and/or arch aortic reconstruction.

Aged↗
PubMed1992

Optic nerve glioma in Japanese patients with neurofibromatosis 1. Case reports and literature review.

Case 1, a 6-year-old boy, had multiple café-au-lait spots, no light perception OS, Lisch nodules OU, pale optic disc OS, enlarged left optic nerve on computed tomographic scan and magnetic resonance imaging, and histopathologically verified pilocytic astrocytoma (glioma). The patient's mother had neurofibromatosis 1 (NF-1). Case 2, a 12-year-old boy, had multiple café-au-lait spots, decreased visual acuity OU, Lisch nodules OU, pale optic discs OU, enlarged optic nerves and chiasm on computed tomographic scan, and histopathologically verified pilocytic astrocytoma. We also examined 38 Japanese patients with NF-1 and found Lisch nodules in 95% and optic nerve glioma in 5%. After reviewing the recent literature, we found that the association of optic nerve glioma and NF-1 in the Japanese population was less than that reported in North America.

Adolescent↗
PubMed1992

Detection of brain-specific gene expression in brain cells in primary culture: a novel promoter assay based on the use of a retrovirus vector.

Promoter activities of the brain-specific genes for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were investigated in brain cells in primary culture with the use of a novel retrovirus vector, pIP200. With this vector, promoter activity can be expressed in terms of beta-galactosidase activity. Differentiation of the primary brain cells to mature glial cells was not affected by treatment with the pIP200 virus vector. The 256-bp 5'-flanking region of the GFAP gene directed astrocyte-specific expression of lacZ. It was silent in fibroblasts, even in multiple copies. The 1.3-kb 5'-flanking region of the MBP gene exhibited strict tissue (oligodendrocyte) specificity under the present assay method but showed some leakiness when integrated into the chromosome in multiple copies. Promoter regions conferring cell type specificity in brain were effectively identified by the present method.

Animals↗
PubMed1992

[Osteoporosis in rheumatoid arthritis].

Rheumatoid arthritis may be associated with generalized, as well as, juxta-articular osteoporosis. To assess the skeletal distribution of bone loss, bone mass was measured in women with rheumatoid arthritis, using single photon absorptiometry and dual energy X-ray absorptiometry. Bone loss was more rapid in the distal metaphyseal region of the radius than in the diaphyseal region. Bone loss in the legs was correlated with gait disturbance and bone loss in the third lumbar vertebra was recognized only in the patients treated with corticosteroids for more than 1 year. These results indicate that rheumatoid arthritis was not universally associated with generalized osteoporosis. Patients treated with corticosteroids are likely to be at risk from generalized osteoporosis.

Absorptiometry, Photon↗
PubMed1991

Differentiating effect of sodium butyrate on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T.

The in vitro effect of sodium butyrate (SB) on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T was investigated. SB was added at the non-toxic but cytostatic concentration of 1 mM. In all these cell lines, SB reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. In PLC/PRF/5, alpha-fetoprotein production and c-myc expression were inhibited. In contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepatitis B virus genome, was increased. In HCC-M and HCC-T, c-myc expression, which was enhanced in the naive state, was reduced. In HCC-M, fos expression was inhibited but the expression of N- and K-ras genes did not change. SB seemed to induce normal or mature properties of hepatocytes in human hepatoma cell lines.

Blotting, Northern↗
PubMed1991

Treatment of chronic hepatitis C with weekly administration of interferon-alpha.

To evaluate the efficacy of weekly administration of interferon (IFN)-alpha, we studied 23 anti-HCV positive patients with chronic hepatitis diagnosed by liver needle biopsy. Thirteen patients received weekly intramuscular injections of 6 MU human lymphoblastoid interferon (HLBI) for 24 weeks, and the other 10 patients were given no treatment. We examined liver-specific idiotype-bearing antibody (LSIA) in the patients' sera. This HLBI treatment was easily tolerated by all the treated patients. In the treated group serum alanine aminotransferase (ALT) level significantly decreased during HLBI treatment. Normalization of serum ALT level by the end of treatment was observed in 7/13 (54%) of the treated patients but in 0% of the non-treated patients. Anti-HCV was detectable in all the patients during the treatment. Those who had high LSIA levels did not respond to HLBI treatment. These results demonstrate that weekly administration of IFN is sufficient to suppress disease activity in patients with chronic hepatitis C and that patients with high LSIA levels are unlikely to respond to IFN therapy.

Alanine Transaminase↗
PubMed1991

Characterization of B cells in human thymus.

The surface characteristics of B cells present in the human thymus were investigated. Cytofluorometrical and immunohistological studies, using anti-human IgM or anti-B cell monoclonal antibodies (mAbs; anti-Leu 12Ab, anti-Leu 16Ab, or L26), revealed that a small number of B cells are present in the human thymus. The thymic B cells were detected only in a low-density cell population, whereas in a high-density cell fraction, only T cells were found. In 15 cases, all of which the thymi were histologically normal, the percentages of B cells in the low-density fraction were 0.28% to 50% (6.8% in average), and Leu 1+ (CD5+) B cells in the low-density fraction were 0.1% to 26% (3.5% in average); approximately 50% of the thymic B cells were Leu 1+ B cells. These results indicate that B cells, especially Leu 1 (CD5)+ B cells, are also present in the human thymus, as suggested from our previous reports on mice.

Adolescent↗
PubMed1991

A potential approach for gene therapy targeting hepatoma using a liver-specific promoter on a retroviral vector.

Recent technological advances made in molecular biology and in vitro culture of human and other mammalian cells have led to broad medical and scientific acceptance of the feasibility of gene therapy for genetic diseases. Cancer might practically be one of the attractive targets for such therapy. For the treatment of cancer, it is important to manipulate the gene of interest such that it is expressed solely in cancer cells. We have developed a tissue-specific gene expression system, based on a tissue-specific promoter on a retroviral vector. A murine ecotropic retroviral vector was constructed in which the Escherichia coli beta-galactosidase gene served as a reporter; it was expressed under control of the albumin enhancer element and promoter. The tissue specificity of this vector was first assessed in vitro, and beta-galactosidase activity was detected exclusively in hepatoma cell lines. This recombinant retrovirus was injected directly into a subcutaneous tumor composed of transplantable murine MH-134 hepatoma cells, and expression of the gene was observed in vivo. Then this recombinant retrovirus was injected via the spleen or directly into the liver, resulting in the gene expression in dividing hepatocytes in partially hepatectomized mice, but not in nondividing hepatocytes in normal mice. Gene transfer specific to dividing hepatocytes and expression by means of retroviral vectors should possess high potential for selective elimination of hepatoma cells surrounded by nondividing normal hepatocytes.

Animals↗
PubMed1991

Proto-oncogene expression in three human hepatoma cell lines, HCC-M, HCC-T and PLC/PRF/5.

Changes of nucleotide sequences and expressions of cellular oncogenes in human hepatoma cell lines, PLC/PRF/5, HCC-M and HCC-T cells, were examined by Southern and Northern blot analyses. The probes used are DNA fragment of myc, N-, H-, K-ras, fos, fms, raf, erb-A, erb-B, and erb-B2 genes and synthetic oligonucleotides corresponding to the part of N-, H-, K-ras genes. The results are as follows. DNA amplification and rearrangement were not detected in these three human hepatoma cell lines. Point mutations at codons 12, 13, and 61 in N- and K-ras genes were not demonstrated in these cell lines. N-, H-, K-ras and myc transcripts were detected in these three cell lines. However, fos gene transcript was detected only in PLC/PRF/5 and HCC-M cells which were derived from hepatitis B related hepatocellular carcinoma and having integrated hepatitis B virus (HBV) DNA. These data showed that there are no specific proto-oncogene expression into RNA except for myc and ras genes, nor DNA rearrangement in these 3 human hepatoma cell lines with regards to at least 10 different oncogenes examined and suggest the relationship between fos gene expression and integration of HBV DNA in host cell DNA.

Blotting, Northern↗
PubMed1991

Effects of long-term cerebral ischemia caused by bilateral carotid artery ligation on the acceleration or the development of hypertension in spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY).

Bilateral carotid artery ligation (BCL) was performed with one week interval between the each operation in male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) aged 4 months. BP rose immediately after unilateral carotid artery ligation (UCL) and BCL in both WKY and SHR due to carotid sinus reflex. Once returning to preoperative levels after both UCL and BCL, BP of SHR and WKY increased again gradually one and 4 months after BCL and thereafter, respectively. BP was significantly higher than that in the controls of each strain, and the BP increment was significantly greater in SHR than in WKY. A significant regional cerebral blood flow (rCBF) increase on the contralateral side of carotid ligation was observed in SHR in contrast to a little change in that of WKY and a reduction of rCBF after BCL was significantly greater in SHR than in WKY. Behavioral activities in SHR were also reduced after BCL. Cerebral edema with nerve cells damage was recognized in SHR. In contrast, little change was found in WKY. On the other hand, upper cervical sympathectomy attenuated convulsive seizures after BCL more markedly in SHR, which survived longer than non-denervated SHR. These results suggest that chronic mild cerebral ischemia caused by BCL with one week interval accelerates the development of severe hypertension in SHR and developed mild hypertension in WKY. Sympathetic innervation might play much more important role in collateral circulation through the vertebrobasilar system in SHR.

Animals↗
PubMed1990

Intracellular pH regulation of normal rat brain: 31P-MRS study.

Intracellular pH changes in rat brain tissue were investigated during low or high extracellular pH induced by acetazolamide or sodium bicarbonate, respectively. Intracellular pH was measured by 31P-MRS in the brain of spontaneously breathing rats under intraperitoneal sodium pentobarbital anaesthesia. Extracellular pH was calculated from the results of blood gas analysis. After intravenous injection of sodium bicarbonate (280 mg/kg), the extracellular pH rose significantly (p less than 0.05) from 7.47 +/- 0.06 to 7.82 +/- 0.15 (mean +/- SE). After administration of acetazolamide (50 mg/kg), the extracellular pH dropped significantly (p less than 0.05) from 7.45 +/- 0.02 to 7.34 +/- 0.03. Despite the changes in extracellular pH, the intracellular pH of rat brain did not change significantly under either condition. The following four factors are thought to contribute to the maintenance of intracellular pH in the normal brain: 1) production and consumption of H+ by brain metabolism, 2) physicochemical buffering, 3) transmembrane transport of H+ and its equivalent, 4) compensatory adaptation of circulatory factors. These mechanisms are not disturbed in the brain of rats that are breathing spontaneously, because the cerebral circulation and energy metabolism are preserved in the normal range.

Acetazolamide↗
PubMed1990

Reliable transient promoter assay using fluorescein-di-beta-D-galactopyranoside substrate.

The promoter region of the mouse myelin proteolipid protein (PLP) gene was cloned into a promoter testing vector, pIP111. The pIP111 vector is a promoterless derivative of pCH110 (SV40 early region promoter-lacZ) and contains the Escherichia coli lpp transcription terminator sequence at the 5' end of the cloning site. The newly constructed PLP-lacZ fusion plasmid (pWP) was transfected into PLP-nonproducing NIH-3T3 fibroblasts or PLP-producing C6 cells. When the measured beta-galactosidase activity in the pWP-transfected cells was normalized to the pCH110-transfected cells (an appropriate control if the SV40 early region promoter functions constitutively in various cell lines), the results suggested that the promoter region of the PLP gene contains the information necessary for initiation of transcription in a C6 cell-specific manner. However, the beta-galactosidase produced in viable cells was also detected by fluorescein-di-beta-D-galactopyranoside (FDG) treatment followed by image analysis using inverted fluorescent microscopy, which allowed the transfection efficiency to be calculated, and the beta-galactosidase activity obtained by the regular ONPG method was normalized with the value obtained. This procedure indicated that the promoter region of the PLP gene did not show C6-specific expression, because the SV40 early-region promoter was 10 times more active in NIH-3T3 cells than in C6 cells. Thus, the standard experiment gave misleading results. As our detection method is simple and can be used to analyze the promoter activity in a single cell, many applications should be possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Endoscopic examination in patients with acute corrosive gastritis].

Clinical significance of endoscopic examination in acute corrosive gastritis were evaluated. Serial endoscopic observations were made in men and rabbits with acute corrosive gastritis. The endoscopic findings were matched against the histological features. The most characteristic endoscopic finding was a brown coloration of the mucosa. Histologically, this corresponded to gangrenous mucosa which was accompanied by necrosis of the gastric wall throughout its entire thickness. When the brown coloration of the mucosa became extensive, chemical peritonitis was induced by the leakage of caustic solution through the wall of the stomach. The recognition of this brown coloration of the mucosa was often hampered by blood coagulo -adhering to the mucosa or brown coloration of the mucosa caused by hematin formation. The latter disappeared 3-6 days after the ingestion of corrosives. It was concluded that endoscopic examination in patients with acute corrosive gastritis should be performed to permit accurate recognition of brown coloration of the mucosa 4-7 days after the ingestion of corrosives.

Acute Disease↗
PubMed1990

Expression of hepatitis B surface antigen in Chang cells transfected with hepatitis B virus DNA.

To investigate hepatitis B virus (HBV) biology in vitro, the transfection of recirculized HBV DNA into Chang cell line was performed. Linear HBV DNA was isolated from recombinant HBV DNA, pHBR105, which includes the whole genome of HBV and was recirculized. Chang cells were transfected with this recirculized HBV DNA by the two different procedures of calcium/phosphate coprecipitation and electroporation. After the transfection, the presence of large nucleated cells with multinuclei and ground-glass cytoplasma were noticed and these cells seemed to proliferate faster than untreated Chang cells. Transient expression of hepatitis B virus surface antigen (HBsAg) was demonstrated in cytoplasma of transfected cells by indirect immunofluorescence. HBsAg was not detected in the culture supernatants by radioimmunoassay. The extra-chromosomal HBV DNA was detected in the transfected cells by both procedures 7 weeks after the transfection by Southern blot analysis but it was lost 4 weeks after that. It was demonstrated that it was possible to transfect Chang cells with HBV DNA and that DNA was functioning to express HBsAg transiently.

Cell Line↗