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Biomedical subjects

H Tsukamoto

Publications and source records attributed to H Tsukamoto.

At least 163 records · Page 9Linked to original sources

Mucosal immune dysfunction associated with alcoholic IgA nephropathy.

We investigated the hypothesis that alcohol-induced changes of the immune system result in IgA nephropathy (IAN). Wistar rats were infused with liquid diet containing alcohol: "alcoholics." Control rats received an isocaloric diet with glucose instead of alcohol. IAN was diagnosed by mesangial IgA deposition. When compared to controls, serum IgA in alcoholic rats with IAN had a fourfold increase and a twofold increase in alcoholics without IAN. The intestinal lamina propria showed overall lymphocyte depletion in alcoholic rats. The decrease was not uniform for all the lymphocyte subgroups: it resulted in a relative increase in IgA-B cells in alcoholic rats with IAN but not in alcoholic rats without IAN. No significant differences were observed between alcoholic and control rats in the percentages of spleen lymphocyte subtypes. We suggest that dysfunction of the mucosal immune system may be related to the induction of IAN in chronic alcohol consumption.

Alcoholism↗

Primary yolk sac tumor of the cerebellar vermis: case report.

A rare case of yolk sac tumor in the cerebellar vermis is reported. A 2-year-old boy developed headaches, vomiting, and an unsteady gait. Later a tumor was demonstrated in the medial part of the cerebellum by gadolinium-enhanced magnetic resonance imaging (MRI). The tumor was totally removed, and the surgery was followed by chemotherapy. Soon after surgery the elevated alphafetoprotein (AFP) levels in the serum and cerebrospinal fluid were observed to decrease to normal levels. Three months later enhanced MRI showed a lesion in the vermis without any elevation of AFP, and the lesion turned out to be a granuloma. Six months after the second surgery a tumor recurred that could not be totally removed. Cranial radiotherapy was given together with chemotherapy, which resulted in a decrease of AFP to the normal range. The patient is doing well without any elevation in AFP at 1 year 6 months after onset. Related problems in the diagnosis and treatment of yolk sac tumors are discussed.

Cerebellar Neoplasms↗

Mitochondrial encephalomyopathies with the mutation of the mitochondrial tRNA(Leu(UUR)) gene.

Four families with mitochondrial encephalomyopathy are described. Probands of three families had typical clinical presentations of mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), but the proband of family 4 lacked strokelike episodes. The mitochondrial DNA mutation of tRNA(Leu(UUR)) (transfer ribonucleic acid specific to leucine (UUR codon)) found in MELAS was examined in muscle DNA obtained from biopsy samples of the probands of four families and the maternal relatives of family 2. The mutation was detected in all muscle samples, and the degree of the mutated DNA was 68% to 84% by Southern blot analysis. However, the clinical patterns of the maternal relatives of family 2 were mild and distinctly different from MELAS. The same mutation was also detected in blood-derived DNA samples of all family members examined, including healthy mothers but not fathers, although the degree of mutation did not correlate with the clinical severity. These results confirmed the maternal inheritance of this disease and suggested that the mitochondrial DNA mutation (tRNA(Leu(UUR))) may cause clinical symptoms other than MELAS. The clinical findings of mitochondrial encephalomyopathy should be reinvestigated in terms of the mitochondrial gene mutation; the polymerase chain reaction method will be useful for screening for this mutation of mitochondrial DNA in blood samples.

Acidosis, Lactic↗

A case of Hallervorden-Spatz disease: progressive and intractable dystonia controlled by bilateral thalamotomy.

We present a 10-year-old girl with Hallervorden-Spatz disease diagnosed clinically from the neurological manifestations and the characteristic MRI findings. Her main symptom, dystonia, was progressive and resistant to medication, but this dystonia was controlled by bilateral thalamotomy. No clinical progression of the symptoms was recognized at 21 months from the last operation.

Child↗

Large-scale culture system of human CD4+ helper/killer T cells for the application to adoptive tumour immunotherapy.

A simple method for the rapid expansion of human CD4+ T cells with both helper and killer functions was established. CD4+ T cells separated from peripheral blood mononuclear cells using immunomagnetic beads were stimulated with immobilised OKT-3 monoclonal antibody (mAb) plus recombinant interleukin 2 (rIL-2) in 96 well culture plates. After 6 day-culture, the CD4+ T cells were restimulated by immobilised OKT-3 mAb for an additional 24 h, then inoculated into concentrated rotary-tissue culture bag and cultured for further 9 days. This procedure yielded a 3000-fold increase in cell number (about 3-5 x 10(9) per bag). Most of the cells (over 96%) continued to express CD4+ antigen and retained their capacity to produce IL-2. The activated CD4+ T cells showed marked cytotoxicity against Fc receptor positive tumour cells in the presence of OKT-3 mAb. Moreover, we succeeded in a specific targeting of the expanded CD4+ helper/killer T cells to c-erb B-2 positive tumour cells by means of anti-CD3 x anti-c-erb B-2 bispecific antibody. These results suggested that our established simple system will be available for the expansion of large number of CD4+ helper/killer T cells which may provide an efficient strategy for adoptive tumour immunotherapy.

Antibodies, Monoclonal↗

Congenital caudal spinal atrophy: a case report.

An infant presented at birth with symmetrical flaccid paraparesis limited to lower legs and feet, and involving the proximal and distal muscle group. Limitation of the ankle joints was noticed. There were no sensory deficits to painful stimuli and no evidence of loss of sphincter control. Muscle CT revealed severe muscle atrophy in the pelvis and lower limbs, and electromyographic study of the bilateral hamstrings showed polyphasic giant potentials. Motor and sensory nerve conduction velocities were within normal limits, and the spinal MRI showed no structural abnormalities in the cord and the lower spine. These features suggest a congenital segmental abnormality at the anterior horn cell level in the lumbosacral spinal cord, which we propose to call "congenital caudal spinal atrophy".

Arthrogryposis↗

Serial magnetic resonance imaging studies in a case of late onset globoid cell leukodystrophy.

The late onset type of globoid cell leukodystrophy (GLD) is a rare disorder and only three magnetic resonance imaging (MR) studies have been reported for this disease. We report a sporadic case of late onset GLD. The illness started at the age of 3 years and 8 months with spastic gait. He became bedridden at the age of 4 years and 7 months. The diagnosis was made by deficient activity of galactosylceramidase in lymphocytes, and the biochemical and morphological examinations of the biopsied sural nerve were also conducted. Computed tomography (CT) and MR study revealed that the degenerative change of the white matter was initially recognized in the occipital and parietal lobes and then extended forward. Literature of the CT or MR findings of GLD is also reviewed.

Biopsy↗

Evaluation of marrow perfusion in the femoral head by dynamic magnetic resonance imaging. Effect of venous occlusion in a dog model.

RATIONALE AND OBJECTIVES: There is a continuing need for a greater sensitivity of magnetic resonance imaging (MRI) in the diagnosis of avascular necrosis (AVN). Previously, it was demonstrated that a dynamic MRI method, with gadolinium-DTPA (Gd-DTPA) enhancement, can detect acute changes not seen on spin-echo images after arterial occlusion in a dog model. Because venous congestion appears to be a more directly relevant hemodynamic abnormality in a majority of clinical AVN cases, the authors extended the dynamic MRI technique to study changes in venous occlusion. METHODS: Dynamic MRI of the proximal femur was performed in five adult dogs before and after unilateral ligation of common iliac and lateral circumflex veins. Sixteen sequential gradient-recalled pulse sequence (GRASS) images (time resolution = 45 mseconds, echo time = 9 mseconds, flip angle = 65 degrees) were obtained immediately after a bolus intravenous injection of 0.2 mmol/kg of Gd-DTPA. Simultaneous measurements of regional blood flow were made using the radioactive microsphere method. RESULTS: After venous ligation, there was a 25% to 45% decrease in the degree of enhancement compared with preligation values on the ligated side. The decrease in cumulative enhancement (integrated over the entire time course) was statistically significant. The occlusion technique was verified by confirming a statistically significant decrease in blood flow determined by the microsphere method. CONCLUSIONS: Dynamic Gd-DTPA-enhanced fast MRI technique can detect acute changes in bone marrow perfusion due to venous occlusion. This technique may have applications in the early detection of nontraumatic AVN.

Animals↗

Alpha-smooth muscle actin expression in tumor and stromal cells of benign and malignant human pigment cell tumors.

We examined the altered expression of alpha-smooth muscle actin (alpha-Sm) in human benign, pre-malignant, and malignant pigment cell tumors by immunohistochemical as well as biochemical (Western blot) analysis using anti-alpha-Sm monoclonal antibody (anti-alpha-Sm MoAb). The expression of alpha-Sm has been revealed immunohistochemically to be associated with mesodermal cells rather than with pigment cells. Western blot analysis using anti-alpha-Sm MoAb detected alpha-Sm expression as a 43-kD band in the extracts from normal papillary dermis, nevus cell nevus, and metastatic melanoma with stromal tissues, but not from primary melanoma with stromal tissues examined. The above findings of alpha-Sm expression by Western blot analysis were further characterized immunohistochemically in terms of the localization at the cellular level as follows. 1) In normal papillary dermis, pericytes encircling capillary vessels showed only positive staining with anti-alpha-Sm MoAb. 2) In nevus tissues, nevus cells were not shown to be positively stained, despite similar positivity of pericytes in normal papillary dermis. 3) In melanoma tissues, alpha-Sm expression of metastatic melanoma detected by Western blot analysis was found to be derived from fibroblasts with smooth-muscle differentiation (myofibroblasts), but not from melanoma cells. Such myofibroblastic stromal changes could not be found on primary melanoma tissue sections, which showed no reactivity in Western blot analysis. We conclude that the major sources of alpha-Sm in benign and pre-malignant pigment cell tumors are capillary pericytes, whereas alpha-Sm found in malignant melanoma tissue is primarily from melanoma-surrounding stromal fibroblasts that were changed to myofibroblasts by some cytokine factor(s), presumably secreted from melanoma cells.

Actins↗

Dysplastic nevus syndrome: melanoma-prone disease.

Regardless of subsequent clinical courses of patients with dysplastic nevi (DN), substantial evidence supporting DN as one of the melanoma-prone diseases is not yet available, especially in sporadic DN, due to the lack of genetic information other than retrospective studies in clinical observation. This study aimed at the immunohistological characterization of sporadic DN distinct from common nevi (CN) and at the evaluation of the potentially of sporadic DN for malignant transformation. We considered our results together with previous immunological and epidemiological reports. We noted the following three immunohistological characteristics. 1) Proliferating cell nuclear antigen (PCNA), one of the markers for active cell division, could be detected on DN cells in junctional nests of only one among ten DN examined but not on CN cells at all. 2) The altered expression of alpha-smooth muscle actin (alpha-Sma), often observed in melanoma cells, could not be detected in DN cells. However, anti-alpha-Sma monoclonal antibody (MoAb) clearly demonstrated distinctive hypervascularity in the stroma surrounding DN when compared with CN. 3) ME491 antigen, which is known to be expressed mainly in the radial growth phase of melanoma, was detected with similar intensity on both DN and CN. These data indicate that DN has a somewhat higher potentiality than CN for cell division and secretion of some cytokines which can induce hypervascularity in the surrounding stroma, but that DN has not yet undergone the significant phenotypic changes observed in melanoma cells. Further advancements in understanding molecular events in DN cells will be of great benefit in setting DN in the multiple oncogenic spectrum from pigment cells to melanoma.

Actins↗

Localization of arachidonate 12-lipoxygenase in canine brain tissues.

The cytosol fraction from a thoroughly irrigated canine cerebrum was subjected to immunoaffinity chromatography using a monoclonal antibody against porcine leukocyte 12-lipoxygenase. Arachidonate 12-lipoxygenase eluted from the column with some retardation. The enzyme, with a specific activity of 9 nmol/min/mg of protein, converted arachidonic acid to 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid. The enzyme was active not only with arachidonic acid, but also with linoleic and alpha-linolenic acids. In contrast, 12-lipoxygenase of canine platelets was almost inactive with linoleic and alpha-linolenic acids, and the platelet enzyme was also distinguished from the cerebral enzyme in terms of reactivity with the anti-12-lipoxygenase antibody. 12-Lipoxygenase activity was also detected in the cytosol fractions of other parts of canine brain: basal ganglia, hippocampus, cerebellum, olfactory bulb, and medulla oblongata.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Time dependency of IgA nephropathy induction in alcohol ingestion.

We investigated the influence of the alcohol ingestion period on the incidence of IgA nephropathy in an animal model. A group of 41 rats received a continuous infusion of liquid diet and alcohol: "alcoholics." A further group of 41 control rats received an isocaloric diet in which the alcohol was replaced by glucose. IgA nephropathy was diagnosed by the presence of intense IgA deposition in the mesangium. At 6 weeks, 60% of the alcoholic rats had IgA nephropathy. The incidence increased until 100% of the alcoholic rats presented the renal disease at 16 weeks. IgA nephropathy was not found in any of the control animals. We conclude that, in this animal model, the incidence of IgA nephropathy is dependent on the time frame of the alcohol ingestion.

Alcoholism↗

Meningioma developed 25 years after radiation therapy for Cushing's disease.

A 44-year-old woman who had been therapeutically irradiated with 45 Gy to the sellar lesion for Cushing's disease has been in remission for 25 years. A large but asymptomatic brain tumor was accidentally found in the right middle fossa by a routine follow-up computed tomography. Upon surgical removal of the tumor, the histology revealed a fibroblastic meningioma. Although the incidence of meningioma following irradiation to pituitary adenoma is rare, a follow-up computed tomography should be taken to any possible late onset, and curable complication.

Adenoma↗

Effects of cell differentiation on the synthesis of the third and fourth component of complement (C3, C4) by the human monocytic cell line U937.

Association of complement synthesis with cell differentiation in U937 cells was investigated using granulocyte-macrophage colony-stimulating factor (GM-CSF), vitamin D3 and interferon-gamma (IFN-gamma) as differentiation-inducing agents. GM-CSF or vitamin D3 enhanced the synthesis of the third component of complement (C3) by U937 cells, but had no stimulatory effect on the synthesis of the fourth component of complement (C4). IFN-gamma increased both C3 and C4 synthesis by U937 cells. Combination of two of these three agents resulted in synergistic enhancement and all three agents caused maximal enhancement of C3 synthesis. Vitamin D3 enhanced IFN-gamma-induced C4 synthesis by U937 cells. These results were confirmed by ELISA and SDS-PAGE after biosynthetic labelling. GM-CSF, vitamin D3 or IFN-gamma increased the expression of complement receptor type 3 (CR3), one of the markers of monocyte/macrophage differentiation. Two of these agents caused a further increase and all three agents maximal increase in CR3 expression. Since C3 was synthesized in parallel with the degree of CR3 expression, the synthesis of C3, but not C4, by U937 cells is thought to be closely related to cell differentiation. It was reconfirmed that the synthesis of C3 and C4 by U937 cells was independently regulated.

Cell Differentiation↗

Synthesis and regulation of the fourth component of complement (C4) in the human monocytic cell line U937: comparison with that of the third component of complement (C3).

Production of the fourth component of complement (C4) by the human monocytic cell line U937 and its regulation were investigated in comparison with the production of the third component of complement (C3) in a cell culture system. Although no detectable C4 was produced by U937 without stimulation, U937 was induced by recombinant interferon-gamma (IFN-gamma) to synthesize C4 in a dose- and time-dependent fashion. The production of C4 was reversibly inhibited by cycloheximide, indicating that it resulted from de novo synthesis. The C4 synthesized by U937 cells was functionally active as assessed by haemolytic assay. SDS-PAGE following biosynthetic labelling showed that subunit structure of C4 synthesized by U937 cells was identical with that of plasma C4 but that molecular weight of alpha-chain was greater than that of plasma C4. We compared the regulation of C4 synthesis with that of C3 synthesis. Although C3 synthesis by U937 cells was enhanced by IFN-gamma, lipopolysaccharide (LPS) and phorbol myristate acetate (PMA), C4 synthesis was induced only by IFN-gamma. LPS and IFN-gamma induced a synergistic increase in C3 synthesis by U937 cells. U937 cells incubated with LPS and IFN-gamma synthesized a greater amount of C4 than those incubated with IFN-gamma alone. Thus it was demonstrated that the synthesis of C3 and C4 was independently regulated. This study shows that the U937 cell line provides a useful model for studies on the synthesis of complement proteins and on the regulation of complement production.

Cell Line↗