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Biomedical subjects

N Tsukada

Publications and source records attributed to N Tsukada.

At least 19 recordsLinked to original sources
PubMed1992

Primary hepatocellular carcinoma with severe hypoglycemia: involvement of insulin-like growth factors.

We report a case of severe hypoglycemia and hepatic masses suspected to be an insulin-like growth factor-II (IGF-II)-producing hepatocellular carcinoma. A 62-year-old man presented with mental disorder in the night and early morning associated with extremely low blood sugar levels (less than 21 mg/dl). Computerized axial tomography and ultrasonography revealed a massive tumor in the right lobe of the liver with multiple secondary nodules, and a tumor thrombus in the portal vein. At autopsy 107 days after admission, the liver weighed 3070 g, histologically showing an Edmondson type II tumor with liver cirrhosis. IGF-II in plasma (899 ng/ml) and tumor tissue (2.4 micrograms/g) was higher than that in normal plasma (374-804 ng/ml) and non-tumor liver tissue (0.2 micrograms/ml), while IGF-I (14 ng/ml) was significantly reduced. IGF-II, probably produced by the liver tumor, appeared to be involved in the mechanism of hypoglycemia.

Carcinoma, Hepatocellular↗
PubMed1992

Spinal cord sarcoidosis: MRI findings in response to treatment.

The unusual case of a 64-year-old female with sarcoidosis involving the spinal cord is reported. Diffuse swelling of the cord with nodular lesions was observed on MRI. The lesions showed a low intensity area on the T1-weighted image. Following the administration of gadolinium-diethylenetriamine pentaacetic acid, the spinal cord, especially the nodular lesions, was diffusely enhanced. Serum levels of anti-endothelial cell antibodies and antinuclear antibodies were elevated. The diagnosis was confirmed by transbronchial lung biopsy which revealed noncaseating granulomas with giant epithelioid cells. The administration of prednisolone, 40 mg/day for 4 weeks, induced a remission.

Autoantibodies↗
PubMed1992

Allergic granulomatous angiitis and peripheral nerve lesion.

We examined 8 cases of allergic granulomatous angiitis (AGA). All cases showed peripheral nerve lesion, comprising damage of all myelinated fibers, which was more severe in larger ones. Immunofluorescent deposits of IgE were detected in the peripheral myelin. There was lymphocyte infiltration both around the endoneural capillaries and in the endoneurium, and an increase of endothelial cells. Nerve ischemia due to obstruction of the vasa nervorum, circulation insufficiency of the small vessels, or immunological abnormality through IgE may play a pathogenetic role in the peripheral neuropathy of AGA.

Child↗
PubMed1991

Increased interleukin-1 production by peripheral blood mononuclear cells in patients with multiple sclerosis.

The production of interleukin-1 (IL-1) by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and inactive phase, in chronic progressive MS patients, in other neurological diseases, and in healthy subjects. Production was determined by measuring the IL-1 concentration in cultures with MNC supernatants using enzyme-linked immunosorbent assay (ELISA). IL-1 in sera of MS patients and healthy subjects also was investigated. MNC IL-1 alpha production was significantly higher in MS patients (180.2 +/- 177.5 pg/ml) than in healthy subjects (66.2 +/- 66.0 pg/ml) (P less than 0.05). Relapsing MS patients in the active phase had significantly higher MNC IL-1 alpha concentrations (360.1 +/- 130.0 pg/ml) than normal subjects (P less than 0.001), but MNC IL-1 alpha production in patients with relapsing MS in the inactive phase (65.3 +/- 52.8 pg/ml) or chronic progressive MS (80.9 +/- 71.9 pg/ml) was not increased significantly. MNC IL-1 beta production in MS patients was not elevated significantly. IL-1 alpha and -1 beta were not detected in sera of MS patients. The correlation between increased IL-1 alpha production and the clinical course of MS suggests that activated MNC may play a role in the pathogenesis of MS.

Adult↗
PubMed1991

Tumor necrosis factor and interleukin-1 in the CSF and sera of patients with multiple sclerosis.

Serum and cerebrospinal fluid (CSF) from 31 patients with multiple sclerosis (MS) were examined to determine the levels of tumor necrosis factor (TNF) and interleukin (IL)-1 alpha (or IL-1 beta) by an enzyme-linked immunosorbent assay. TNF was detected in 29 (93.5%) of CSF from 31 cases of MS. TNF was also detectable in 100% of CSF from patients with acute relapsing MS in exacerbation. Patients with acute relapsing MS in exacerbation showed significantly higher CSF levels of TNF as compared with either those in remission or the controls (P less than 0.001 and P less than 0.0001, respectively). Increased levels of TNF were also detected in 35.5% of the MS sera, and especially in those with acute relapsing MS in exacerbation. Increased TNF levels were also frequent in the CSF and sera of patients with Guillain-Barré syndrome (GBS), which is also a demyelinating disease. No IL-1 alpha (or IL-1 beta) was detected in either CSF or sera of 31 MS patients. It is considered likely that TNF CSF levels may reflect disease activity in MS.

Adult↗
PubMed1991

Soluble CD4 and CD8 in the peripheral blood of patients with multiple sclerosis and HTLV-1-associated myelopathy.

We evaluated the presence of soluble (s) CD4 and sCD8, released from activated T cells, in the sera of patients with multiple sclerosis (MS) and human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay (ELISA). In addition, peripheral blood T cell subsets in patients with MS and HAM were analyzed by single and two color flow cytometry. The serum level of sCD8 was significantly elevated in MS patients as compared with controls (p less than 0.001). Sera from patients with an exacerbation of acute relapsing MS showed a higher sCD8 level than the patients in remission or controls (p less than 0.01 and p less than 0.001, respectively). The serum levels of both sCD4 and sCD8 were also significantly elevated in patients with HAM (p less than 0.001 and p less than 0.001, respectively). In addition, a significantly increased serum level of soluble interleukin-2 receptor (sIL-2R) was found in patients with HAM as compared with that of controls (p less than 0.001). These observations suggest that CD8 cells may be activated in the peripheral blood of patients with MS and sCD8 may be related to clinical activity, but that both CD4 and CD8 cells may be activated in the peripheral blood of patients with HAM.

Adult↗
PubMed1991

Motility of bile canaliculi in the living animal: implications for bile flow.

Modern fluorescence microscopic techniques were used to image the bile canalicular system in the intact rat liver, in vivo. By combining the use of sodium fluorescein secretion into bile, with digitally enhanced fluorescence microscopy and time-lapse video, it was possible to capture and record the canalicular motility events that accompany the secretion of bile in life. Active bile canalicular contractions were found predominantly in zone 1 (periportal) hepatocytes of the liver. The contractile movements were repetitive, forceful, and appeared unidirectional moving bile in a direction towards the portal bile ducts. Contractions were not seen in the network of canaliculi on the surface of the liver. Cytochalasin B administration resulted in reduced canalicular motility, progressive dilation of zone 1 canaliculi, and impairment of bile flow. Canalicular dilations invariably involved the branch points of the canalicular network. The findings add substantively to previous in vitro studies using couplets, and suggest that canalicular contractions contribute physiologically to bile flow in the liver.

Animals↗
PubMed1991

[Subsets of peripheral blood lymphocytes and ageing in patients with SMON].

Recent clinical problems in patients with subacute myelo-optico-neuropathy (SMON) arise mainly from complications associated with the disease. Some of them show the association of autoimmune diseases. Furthermore, it has been reported that some kinds of autoantibody and hyperglobulinemia are frequently seen in patients with SMON. In order to examine whether ageing and clioquinol intoxication in the past may be implicated in the immunological system of the patients, we investigated subsets of peripheral blood lymphocytes including OKT3, OKT4, OKT8, OKIa1 and Leu7, in 31 patients with SMON, who lived in Nagano Prefecture. The levels of OKT8 (% positive cells), which are known to decrease with age actually increased with age in the peripheral blood of patients with SMON. The levels of OKT4 decreased with ageing, as did the OKT4/OKT8 ratios. The percentage of OKIa1 also significantly increased with age in the peripheral blood of patients with SMON compared to that of the controls (p less than 0.01 or p less than 0.001). It is considered unlikely that the effect of ageing on subsets of lymphocytes can be implicated in these immunological abnormalities of SMON patients, but it seems likely that the immune systems (B cell or T cell) of SMON patients are activated by factors other than ageing in subsets of lymphocytes.

Aged↗
PubMed1991

Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated.

The motility of bile canaliculi was examined in hepatocyte couplets permeabilized with palmitoyl lysophosphatidyl choline in a dosage regimen that drastically affected secretory function, yet maintained relative integrity of the cellular cytoskeleton. The permeabilized cells showed no exclusion of trypan blue, notable cytoplasmic organelle and membrane damage, and no uptake or secretion of either fluorescein diacetate or sodium fluorescein. However, bile canalicular structure remained relatively intact and actin and myosin were localized immunocytochemically in the pericanalicular region. Coincident with the administration of 1 mM ATP, 2 mM Mg2+, and 1 microM Ca2+, the canaliculi contracted with partial or complete luminal closure. ADP, AMP, or AMP-PCP could not be substituted for ATP. A dose-dependent relationship was shown between ATP concentration and canalicular contraction rate. The permeabilization procedure also provided enhanced visualization of pericanalicular microfilaments, believed to be actin filaments, and their organization into two layers: an inner membrane-associated network, and an outer filament bundle that inserted into belt junctions (zonulae adherentes). The organization of the microfilament belt of contiguous hepatocytes was such that it formed a circumferential band of microfilaments around the canaliculus. It is analogous to contractile filament belts found in the apical terminal web region of other epithelia. It was also observed that with canalicular luminal closure, there was a change in the organization of the pericanalicular microfilaments. It is concluded that in hepatocyte couplets, differential sensitivity of cell components to permeabilization can be achieved with palmitoyl lysophosphatidyl choline. In addition, the results provide evidence that the bile canaliculus has the capacity to be a contractile structure even in the absence of secretion, that canalicular contraction is ATP-dependent, and hence is a dynamic process.

Actin Cytoskeleton↗
PubMed1990

[Study on prototype cylindrical HAP].

Hydroxyapatite (HAP) is currently utilized as biomaterials for implantation or reconstruction of bone defect in dentistry. In order to obtain better physical properties and biocompatibility, we have developed cylindrical sintered porous HAP which has longitudinal internal tubules. We measured compressive strength and specific surface area of cylindrical HAP. In the results, compressive strength was more 300MPa on average and specific surface area was 1.7-2.4 folds as HAP ceramics commercially available. This result indicates new bone formation. Cylindrical HAP used was subsequently applied to lower premolars and molars of male beagle dogs (1.5 years). We have implanted cylindrical HAP to bone defect of postextraction of tooth followed to sacrifice six months after. Specimens of bone block were stained with Villanueva bone stain and observed with fluorescence microscope and scanning electron microscope. New tissue formation was observed invading into tubules of 27 microns diameter of cylindrical HAP particles. This new tissue was confirmed to be bone tissue because the proportion of Ca to P was 1.616 obtained by energy dispersive X-ray analyzer.

Alveolar Bone Loss↗
PubMed1989

Autoantibodies to brain endothelial cells in the sera of patients with human T-lymphotropic virus type I associated myelopathy and other demyelinating disorders.

We examined the sera of 21 cases of human T-lymphotropic virus type I (HTLV-1)-associated myelopathy (HAM), 30 cases of neuro-Behçet (N-B) syndrome, and 36 cases of multiple sclerosis (MS) for the presence of autoantibodies to brain endothelial cells by enzyme-linked immunosorbent assay (ELISA) using cultured brain endothelial cells. The concentrations of immunoglobulin G (IgG) which bound to brain endothelial cells were significantly increased in the sera of patients with HAM before (P less than 0.001) and after (P less than 0.01) blocking Fc receptors compared to those of controls. The levels of IgG binding to brain endothelial cells were also significantly increased in the sera of patients with N-B syndrome (P less than 0.01), and MS (P less than 0.001) especially those in an exacerbation compared to those of controls regardless of blocking Fc receptors. These results suggest that IgG binding to brain endothelial cells may be mediated via an immunologically specific antigen-antibody interaction as a result of the blood-brain barrier (BBB) damage in cases of HAM, N-B syndrome and MS.

Adult↗
PubMed1989

Autoantibodies to each protein fraction extracted from cerebral endothelial cell membrane in the sera of patients with multiple sclerosis.

Damage to the blood-brain barrier (BBB) occurs in multiple sclerosis (MS), probably due to an immunological mechanism. Anti-endothelial cell antibodies may play a pathogenetic role in the BBB damage. Our previous studies led us to search for which protein fraction extracted from cerebral endothelial cell membrane was reactive to antibodies in the sera of patients with MS. The antibodies to each protein fraction extracted from the rat cerebral endothelial cell membrane were studied in patients with MS, other neurological diseases and controls using an enzyme-linked immunosorbent assay (ELISA) method. The patients with active relapsing MS (P less than 0.01) displayed significantly higher levels of immunoglobulin G (IgG) binding to the endothelial cell membrane fraction than did the controls. The sera of the same patients (P less than 0.001) also showed significantly higher levels of antibodies to fraction I (8.0 kDa) than did the normal controls. The high levels of IgG binding to fraction II (11.0 kDa) and III (12.3 kDa) were significantly increased in the sera of patients with active relapsing MS compared to normal controls (P less than 0.01). The immune response to the protein fraction extracted from the cerebral endothelial cell membrane fraction may indicate a result of the BBB damage in the case of MS.

Adolescent↗
PubMed1989

[Detection of immune complexes in the sera and around the muscle fibers in a case of myasthenia gravis and polymyositis].

A case of myasthenia gravis accompanied with polymyositis and malignant thymoma, detected immune complexes in the sera and around the muscle fibers, was described. A 37-year-old woman was admitted to Shinshu University Hospital in September, 1987 because of dyspnea, dysphagia and muscle weakness. She first noticed her right blepharoptosis 3 weeks before admission. Weakness of all four limbs and myalgia of lower extremities were noticed one week later. These symptoms got worse and nocturnal dyspnea, dysphagia and easy fatigability at mastication appeared. On admission, she looked ill and neurological examination revealed left blepharoptosis, bilateral facial weakness, weakness of all four limbs, more prominent in proximal muscles and tenderness of lower extremities. Edrophonium test was positive, improving her muscle weakness. Laboratory examination revealed the elevated serum levels of CK, the increased titre of circulating immune complexes and high titres of acetylcholine receptor antibodies and anti-skeletal muscle antibodies. Electromyographic study showed myogenic pattern and Harvey-Masland test revealed waning at low frequency stimulation. Muscle biopsy showed marked perivascular infiltration of lymphocytes, accompanied by phagocytosis and interstitial fibrosis. IgG deposits were shown around the muscle fibers exclusively around the infiltrates of mononuclear cells. Granular deposits of C3 were also shown specifically around the muscle fibers exclusively around the infiltrates of mononuclear cells. Thymectomy was performed on September 21, 1987. Invasion of thymoma, predominantly lymphocytic type, to right lung and pericardium was observed histologically. After thymectomy, she got better. Immunological data and immunohistochemical examination of the present case suggest that in the case of myasthenia gravis accompanied with polymyositis and malignant thymoma, immune complexes may play a primary role on the pathogenesis of myositis.

Adult↗
PubMed1989

[A case of Sjögren's syndrome with mononeuritis associated with high levels of circulating immune complexes].

A 32-year-old woman with Sjögren's syndrome accompanied by mononeuritis of right lower extremity was described. She admitted Shinshu University Hospital with the chief complaints of Raynaud's phenomenon and generalized lymphadenopathy. One year before admission Raynaud's phenomenon of right hand was first noticed. One month later she complained of a gritty sensation in the eyes and severe dryness of the mouth. On admission, she had systemic lymphadenopathy. Neurological examination revealed decreased light touch and pinprick sensations and decreased deep tendon reflexes in right lower extremity. Lip biopsy revealed marked mononuclear cell infiltrates around the salivary glands. Laboratory data included IgG 3,007 mg/dl, circulating immune complexes 1,200 micrograms AHGeq/ml (Raji-cell ELISA), anti-nuclear antibody 2,560X (speckled pattern) and anti-SSA antibody 256X. The levels of total protein, IgG and immune complexes were increased in the CSF of this patient. Sural nerve biopsy revealed a decreased number of large myelinated fibers and perivascular lymphocyte infiltration of vasa nervorum. Direct immunofluorescent staining showed deposition of IgG and C3 in the endoneural vessel walls. The increased level of immune complexes were decreased in the sera of the patient, accompanied by remission. These results suggest that immune complexes may be involved in the pathogenesis of a mononeuritis associated with Sjögren's syndrome.

Adult↗
PubMed1988

Autoimmune encephalomyelitis in rhesus monkeys induced by immunization with cerebral endothelial cell membrane.

It is postulated that multiple sclerosis might be an autoimmune demyelinating disease of the central nervous system (CNS). The mechanisms involved are unknown but, since the blood-brain barrier (BBB) is damaged, injury to endothelial cells is likely to have occurred. Our previous studies have led us to investigate the autoimmune effect of injuring the blood-brain barrier by immunizing rhesus monkeys with an endothelial cell membrane from the same kind of animals. The immunized animals developed a chronic or a relapsing neurological illness. Histological and ultrastructural examinations of the brain in the acute stage showed infiltrates of mononuclear cells around the blood vessels of the white matter of cerebrum, cerebellum, pons and midbrain, while in the chronic phase, large areas of demyelination and remyelination, especially in the white matter regions, were present. The animals immunized with extraneural antigen, an endothelial cell membrane obtained from human umbilical cord, developed no neurological illness. This results indicate that the brain endothelial cell membrane has an inflammatory encephalitogenic activity which could produce widespread demyelination in animals. The animal model described here may prove to be useful in the pathogenetic investigation of human autoimmune demyelinating diseases.

Animals↗
PubMed1988

Autoradiographic demonstration of gastrin-releasing peptide-binding sites in the rat gastric mucosa.

The location of [125I]iodotyrosyl gastrin-releasing peptide-binding sites in the rat fundic mucosa was studied. Peptide specificity was demonstrated by competitive binding studies using the addition of a large amount of cold gastrin-releasing peptide or substance P. Autoradiography of the stomach tissue was carried out by freeze-drying, embedding in Epon, wet-sectioning with ethylene glycol, and dry-mounting the emulsion film by the wire-loop method to prevent loss of the labeled substance. Specific binding sites of gastrin-releasing peptide were found on D cells, surface mucus cells, and parietal cells, whereas few binding sites were seen on the chief or mucus neck cells.

Animals↗