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Biomedical subjects

H Tsukamoto

Publications and source records attributed to H Tsukamoto.

At least 127 records · Page 7Linked to original sources
PubMed1995

Experimental liver cirrhosis induced by alcohol and iron.

To determine if alcoholic liver fibrogenesis is exacerbated by dietary iron supplementation, carbonyl iron (0.25% wt/vol) was intragastrically infused with or without ethanol to rats for 16 wk. Carbonyl iron had no effect on blood alcohol concentration, hepatic biochemical measurements, or liver histology in control animals. In both ethanol-fed and control rats, the supplementation produced a two- to threefold increase in the mean hepatic non-heme iron concentration but it remained within or near the range found in normal human subjects. As previously shown, the concentrations of liver malondialdehyde (MDA), liver 4-hydroxynonenal (4HNE), and serum aminotransferases (ALT, AST) were significantly elevated by ethanol infusion alone. The addition of iron supplementation to ethanol resulted in a further twofold increment in mean MDA, 4HNE, ALT, and AST. On histological examination, focal fibrosis was found < 30% of the rats fed ethanol alone. In animals given both ethanol and iron, fibrosis was present in all, with a diffuse central-central bridging pattern in 60%, and two animals (17%) developed micronodular cirrhosis. The iron-potentiated alcoholic liver fibrogenesis was closely associated with intense and diffuse immunostaining for MDA and 4HNE adduct epitopes in the livers. Furthermore, in these animals, accentuated increases in procollagen alpha 1(I) and TGF beta 1 mRNA levels were found in both liver tissues and freshly isolated hepatic stellate cells, perisinusoidal cells believed to be a major source of extracellular matrices in liver fibrosis. The dietary iron supplementation to intragastric ethanol infusion exacerbates hepatocyte damage, promotes liver fibrogenesis, and produces evident cirrhosis in some animals. These results provide evidence for a critical role of iron and iron-catalyzed oxidant stress in progression of alcoholic liver disease.

Animals↗
PubMed1995

Cytokine gene expression by Kupffer cells in experimental alcoholic liver disease.

Kupffer cell-derived cytokines are believed to play pivotal paracrine roles in the pathogenesis of alcoholic liver disease (ALD). To evaluate this hypothesis, Kupffer cell gene expression of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-6, and transforming growth factor-beta 1 (TGF beta 1) were directly examined in the rat model of ALD. Kupffer cells were isolated from the model after 10 and 17 weeks of intragastric ethanol infusion. These two durations resulted in focal hepatocellular injury and liver fibrogenesis, respectively. Oxidative stress as assessed by the hepatic level of thiobarbituric acid reacting substances, was evident at 10 weeks but more pronounced at 17 weeks. The steady state messenger RNA (mRNA) levels of the cytokines were examined by Northern blot analysis using RNA samples from freshly isolated Kupffer cells, and the release of the cytokines was quantitated ex vivo using a 3-day culture. The mRNA levels of TNF alpha and TGF beta 1 were significantly increased by 183% and 204% at 10 weeks and 231% and 295% at 17 weeks in the ethanol-fed rats, respectively. Ex vivo release of TNF activity by control Kupffer cells was undetectable or very low (< 2U/10(5) cells/18 hours) at both time points, but the cells from the ethanol-fed animals secreted appreciably more TNF (27.8 +/- 7.6 U at 10 weeks and 40.4 +/- 10.3 U at 17 weeks). The release of the latent TGF beta 1 protein was also coordinately increased by 143% at 10 weeks and 238% at 17 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1995

Bispecific antibody-mediated cytotoxicity by CD4+ and CD8(+)-activated T cells generated from leukemia patients after allogeneic bone marrow transplantation.

The F(ab')2 bispecific antibody (BSAb) was prepared from anti-CD3 moAb and anti-CD10 moAb. The BSAb could react with both CD3+ T cells and CD10+ leukemia cells and triggered T cell-mediated cytotoxicity. To apply the BSAb to prevention of leukemic relapse after BMT, we investigated the generation of both CD4+ and CD8+ anti-tumor effector T cells from patient's PBMC 14 days after BMT. Neither CD4+ T cells nor CD8+ T cells, which were activated with immobilized anti-CD3 moAb plus IL-2, could lyse CD10+ leukemia cells by themselves, but they showed augmented cytotoxicity against CD10+ leukemia cells by targeting with anti-CD3 x anti-CD10 BSAb. Moreover, the activated CD4+ T cells were demonstrated to produce IL-2 and IFN-gamma when they were cultured with CD10+ leukemia cells in the presence of the BSAb. The BSAb-mediated cytotoxicity of activated T cells was demonstrated not only against the recipient leukemia cells but also against third party leukemia cells. These results suggested that anti-CD3 x anti-CD10 BSAb might be a good tool to prevent relapse after BMT in combination with activated CD4+ T cells and CD8+ T cells.

Antibodies, Monoclonal↗
PubMed1995

A progressive occlusion of the internal carotid arteries in a case of adult-onset moyamoya disease.

Progressive occlusions of the intracranial portions of ICAs are already established phenomena in childhood-onset moyamoya disease, but they have not yet been demonstrated in adult-onset patients. A patient with moyamoya disease manifested at 25 years of age was examined with cerebral angiography at 27 and 45 years of age. The angiograms taken at 27 revealed that the right ICA was completely occluded at the clinoidal portion, while the left one was patent and the occlusive/stenotic change was limited to the terminal portion. Angiograms taken 17 years later revealed that the right ICA was occluded at the origin, while the left one concentrically narrowed at the origin, then tapered off and was occluded at the clinoidal portion. The present case suggests that the ICA occlusion of moyamoya disease is not limited to the intracranial segment but progresses to the cervical segments, even in adult-onset patients. Based on these findings, two different groups of adult-onset moyamoya disease may exist; one in which the occlusive disorder has been completed by the time clinical manifestations appear and thereafter decreases, while the other group consists of occlusive disorders that steadily progress to the original portion of ICA.

Age of Onset↗
PubMed1995

Isoforms of glucose transporter in the iris-ciliary body.

Isoforms of the facilitated glucose transporter (GLUT) were identified in the iris-ciliary body. Western blot analysis showed that GLUT1 and GLUT4 proteins were expressed in the rat iris-ciliary body. In addition, the content of GLUT proteins in the rabbit iris-ciliary body was estimated by specific [3H]cytochalasin B binding assay. The content of GLUT proteins was found to be more abundant in the iris-ciliary body than in the cerebral cortex. The utilization of glucose in the iris-ciliary body and the transport of glucose into the aqueous humor are suggested to be mediated by GLUT1 and GLUT4 proteins.

Animals↗
PubMed1994

Infantile progressive spinal muscular atrophy with ophthalmoplegia and pyramidal symptoms.

Two siblings presented with identical features of progressive peripheral paralysis of the lower motor neuron type, pyramidal signs, cranial nerve palsy which included external ocular palsy and deafness, and internal ocular palsy; both died before 1 year of age. Pathologic examination of the central nervous system in both patients revealed degeneration and loss of spinal and cranial nerve motor nuclei, including the oculomotor nucleus. In addition, there was degeneration of the Edinger-Westphal nuclei and demyelination of the corticospinal tract under the midbrain. Although spinal cord lesions were indistinguishable from those of Werdnig-Hoffmann disease, the 2 patients are not considered to have Werdnig-Hoffmann disease from the clinicopathologic findings.

Brain↗
PubMed1994

Imaging study on the mode of development and changes in avascular necrosis of the femoral head in systemic lupus erythematosus: long-term observations.

To find out when and how avascular necrosis of the femoral head (ANFH) develops in patients with SLE who are receiving corticosteroids, we carried out a 3-yr prospective study using imaging methods. Twenty-three patients with SLE who were free of hip pain and radiographically negative were enrolled in the study. Initially, abnormal findings characteristic of ANFH were detected in eight (35%) and six (26%) patients on MRI and radionuclide uptake bone scanning, respectively. During a 3-yr observation period abnormalities on MRI, bone scanning and radiography were found in four, five and four patients, respectively and three patients developed hip pain. Analyses of imaging changes demonstrated that only a small proportion of patients (2/8, 25%) who initially showed abnormal MRI progressed to be radiographically positive for ANFH over the 3 years. High doses of corticosteroids over the 3-yr period were to be responsible for the emergence of change in MRI abnormalities. It is also suggested that abnormal MRI findings tend to develop either within a relatively short interval after the start of corticosteroid treatment or are associated with the exacerbation of SLE.

Adolescent↗
PubMed1994

The altered expression of alpha-smooth muscle actin in basal cell epithelioma and its surrounding stroma: with special reference to proliferating cell nuclear antigen expression and adenoid differentiation.

Altered expression of alpha-smooth muscle actin (alpha-SMA) is known to indicate the morphological, tumorigenic and immunological changes occurring in tumour and stromal cells. The purpose of this study was to analyse the dynamics of alpha-SMA expression in human basal cell epithelioma (BCE) cells and their surrounding stromal cells, in the process of differentiation towards cutaneous appendages such as hair, sebaceous, apocrine and eccrine glands. Using anti-alpha-SMA specific monoclonal antibody (MAb), 17 of 36 BCEs (47%) were shown to express alpha-SMA, despite the usual absence of alpha-SMA in all eukaryotic cells except muscle cells. Solid, adenoid and sclerosing types of BCE expressed alpha-SMA more frequently, and in greater amount, than cystic, keratotic and superficial types. Furthermore, the expression of alpha-SMA in BCE cells significantly paralleled the expression of proliferating cell nuclear antigen (PCNA) in these cells. Thus, the altered expression of alpha-SMA may reflect the growing properties of BCE cells under the specific cellular regulations for differentiation. In addition, we have found anti-alpha-SMA MAb-positive fibroblasts with smooth muscle differentiation (myofibroblasts) in desmoplastic stroma surrounding BCE nests in 13 of 36 cases (36%). Coincidental expression of alpha-SMA in both BCE cells and stromal cells was found in nine of the 13 cases (69%), indicating the possibility of the induction of myofibroblastic stromal changes in surrounding tissues by cytokines secreted from BCE cells [e.g. basic fibroblast growth factor (bFGF)-like factor].

Actins↗
PubMed1994

Tissue distribution of an immunogenic melanoma associated antigen, D-1.

A human melanoma-associated antigen immunogenic in patients was recently identified by screening an expression cDNA library constructed from cultured human melanoma cell line with sera from patients with melanoma. The nucleic acid sequence of the cloned D-1 cDNA has no significant homology with previously reported mammalian genes. The cDNA D-1 encodes a peptide of about 37 kDa, which showed fivefold higher reactivity with sera from patients with melanoma than with sera from normal donors. In order to detect D-1 gene expression in vivo, in-situ hybridization and immunostaining with cRNA probe and murine anti-D-1 sera were carried out on surgically removed tissues. Digoxigenin-labeled cRNA D-1 was exclusively hybridized with mRNA in the cytoplasm of melanoma cells but not with keratinocytes and fibroblasts adjacent to melanoma nests. Polyclonal anti-D-1 antibodies were obtained by immunization of Balb/c mice with recombinant D-1 peptide and clearly reacted with melanoma cells but not with keratinocytes and fibroblasts, similar to the results of in-situ hybridization. The above information will help to assess the suitability of recombinant D-1 peptide to implement active specific immunotherapy in patients with melanoma.

Animals↗
PubMed1994

Cerebellopontine angle meningioma associated with cranial accessory nerve neurinoma--case report.

A 46-year-old female presented with a rare association of cerebellopontine (CP) angle meningioma with accessory nerve neurinoma manifesting as headache, occasional diplopia, speech disturbance, swallowing difficulty, and unsteady gait. Magnetic resonance imaging demonstrated a large tumor in the left CP angle. The tumor was totally removed through a lateral suboccipital approach. During the operation another smaller tumor was found originating from the cranial accessory nerve and was also totally removed. Histological examination found that the larger tumor was a meningotheliomatous meningioma and the smaller an Antoni type A neurinoma. The symptoms were apparently due to the larger tumor. Careful examination of neuroimages is necessary even after the main lesions responsible for the symptoms are identified.

Accessory Nerve↗
PubMed1994

[CT & MRI findings of refractory vasculitis].

We described CT and MRI findings of various refractory vasculitis. Refractory vasculitis must be divided into two categories including one group with major vascular involvement and another one with small or microvascular involvement. In cases with major vessel involvement such as Takayasu's arteritis, Kawasaki disease or vasculo-Behçet disease, CT and MRI depicted direct findings of vessels itself including stenosis, obstruction, aneurysm, and wall thickening. On the other hand, CT and MRI showed various extravascular findings in cases with small or microvascular involvement, such as CNS involvement in collagen vascular disease, pulmonary lesions in Wegener's granulomatosis and Churg-Strauss syndrome, and peritoneal lesion in SLE. Our results suggest that CT and MRI findings reflect various vascular condition of refractory vasculitis and correspond to various pathology.

Humans↗
PubMed1994

[A case of intracerebral tuberculoma: clinical characteristics and MRI findings].

A case of intracerebral tuberculoma treated surgically was reported. A 47-year-old man was admitted to our hospital because of progressive left hemiaparesis over the previous 5 months. A computerized tomography scan showed a well enhanced mass associated with a marked perifocal edema. T1 weighted magnetic resonance imaging (MRI) revealed an isosignal ring around the heterogenous low intensity mass. A low intensity area just interior to this ring was also visualized both in T1 and T2 weighted images. Although the clinical course was unusually long, this was diagnosed as a metastatic brain tumor. He underwent a right frontal craniotomy and a well circumscribed, yellowish, firm mass was totally extirpated. Pathohistologically, this mass was considered to be a tuberculoma though the tuberculous bacilli could not be identified in Ziehl-Neelsen staining. His hemiplegia improved much and his ambulation was restored. Since tuberclomas are quite rare in developed countries, the diagnosis of intracerebral tuberculomas would be extremely difficult unless tuberculosis was verified in some other organs. The auxiliary examinations even by using MRI have often given little information which would assist diagnosis. However, based on pathological findings, the ring appearance and low intensity area medial to the ring in the outer part of the tuberculoma shown in MRI of our patient seemed to represent a chronic granulomatous inflammation and gave a clue to rule out the suspicion of metastatic brain tumors. To make a correct diagnosis of intracerebral tuberculomas, multidisciplinary consideration is mandatory.

Antitubercular Agents↗
PubMed1993

Case of ring chromosome 7: the first report of neuropathological findings.

We report on a boy with ring chromosome 7 who had severe mental retardation, growth failure, microcephaly, cleft lip and palate, café-au-lait spots, nevus flammeus, and genital abnormalities, and died of pneumonia at age 20 months. On autopsy he had fusion of the anterior cerebral hemispheres, accompanied by agenesis of olfactory bulbs and tracts, closely resembling those found in semilobar holoprosencephaly. In addition, heterotopic Purkinje cell clusters in the cerebellar white matter, absence of pigmentation within the brainstem pigmented neurons, and severe hypomyelination in the whole brain were noted. The patient may represent the most severe manifestation of ring chromosome 7, and this is the first detailed neuropathological report on this subject.

Abnormalities, Multiple↗
PubMed1993

Effect of T cells on the complement production by monocytes.

We studied the role of T cells in the regulation of C3 or C4 production by monocytes. While cocultured T cells reduced C3 production, they enhanced C4 production by monocytes in a number-dependent manner. Interleukin-2 enhanced these effects of T cells on C3 and C4 production, indicating that activated T cells had greater effects on complement production by monocytes. CD4+ T cells had greater effects than those of CD8+ T cells on the C3 or C4 production by monocytes, indicating that CD4+ T cells were mainly involved in the regulation of C3 and C4 production by monocytes. T-cell-conditioned medium (T-CM) also decreased C3 and enhanced C4 production, but the effect of T-CM on C3 and C4 production was less remarkable than that of T cells. T cells separated by transwell inserts from monocytes had similar effects as those of T-CM on complement production. Anti-IFN-gamma antibody completely blocked the suppressing effect on C3 production and partially blocked the stimulating effect of T cells on C4 production. These results indicate that T cells regulate C3 or C4 production by monocytes via IFN-gamma as a humoral factor. Moreover, the stimulating effect of T cells on C4 production was partially blocked when monocytes and T cells were incubated with anti-CD2, anti-LFA-1, and anti-HLA-DR antibodies, and anti-CD2 partially blocked the suppressing effect of T cells on C3 production by monocytes. These results indicate that T cells modulate the C3 and C4 production by monocytes not only via a humoral factor but also via a direct interaction with monocytes.

Cell Communication↗