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Biomedical subjects

N Tsukada

Publications and source records attributed to N Tsukada.

At least 73 records · Page 4Linked to original sources

[Significance of cytokines and other immunological mediators in neuroimmunological diseases].

Investigation in neuroimmunological disorders has delineated multiple effector mechanisms that operate to produce inflammatory demyelination. There is much evidences to implicate cytokines in the pathogenesis of these disorders and the role and significance of measurement of various inflammatory mediators, including cytokines are reviewed. Cytokines, such as TNF, IL-1, and IFN-gamma are involved in the inflammatory demyelinating process by enhancing vascular permeability, modulating inflammatory cell-cell interactions and injuring the blood-brain barrier. Recent reports suggest that TNF, IL-2, IL-6, and other immunological mediators, such as sIL-2R, sTNF-R and sICAM-1, reflect the disease activity and can serve as a marker of acute inflammation in several neuroimmunological diseases. A better understanding of these mediators, operating on inflammatory demyelination, may help to clarify the pathogenesis of neuroimmunological diseases and to devise more efficacious therapy.

Biomarkers↗

Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage.

In contrast to patients with disseminated intravascular coagulation (DIC) due to other causes, patients with acute promyelocytic leukemia (APL) receiving standard cytotoxic chemotherapy can be treated safely with antifibrinolytic drugs for prophylaxis of hemorrhage, without the occurrence of thromboembolic complications. However, such drugs should be used cautiously in APL patients who are receiving all-trans retinoic acid (ATRA) differentiation therapy. We report here a patient with APL who had fatal thromboembolism after receiving ATRA and tranexamic acid therapy.

Acute Kidney Injury↗

[Activated T cells in the peripheral blood of patients with subacute myelo-optico-neuropathy (SMON)].

It has been reported that some kinds of immunological abnormalities are more frequently seen in patients with subacute myelo-optico-neuropathy (SMON), as compared with normal subjects. In order to examine whether ageing and clioquinol intoxication in the past may be implicated in the immunological disorders of the patients, we investigated soluble interleukin-2 receptors (sIL-2R) and an appearance of HLA-DR positive T cells using two color flow cytometry analysis in the peripheral blood of 29 patients with SMON, who lived in Nagano Prefecture. The mean level of HLA-DR positive T cells in the total of SMON patients was significantly high as compared with that of normal subjects (p < 0.001). The mean levels of HLA-DR positive T cells were also significantly high in SMON patients in their fifties and younger, sixties, and seventies and older, respectively, as compared with those of normal subjects (p < 0.05, respectively). The mean level of sIL-2R in the total of SMON patients was significantly high as compared with that of normal subjects (p < 0.01). The mean levels of sIL-2R were also high in SMON patients in their fifties and younger, sixties, and seventies and older. An especially significant increase was seen in SMON patients in their sixties (p < 0.01). SMON patients with higher levels of HLA-DR positive T cells tended to have higher levels of sIL-2R, and statistical analysis showed a significant correlation between them (r = 0.696, p < 0.001). An increase in HLA-DR positive T cells and sIL-2R indicates an increase in activated T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Increased levels of circulating intercellular adhesion molecule-1 in multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy.

We evaluated the presence of soluble intercellular adhesion molecule-1 (sICAM-1) antigen in the sera of patients with multiple sclerosis and human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay. Patients with multiple sclerosis in the active phase had higher sICAM serum levels than did control subjects (p < 0.01). In addition, a significantly increased serum level of sICAM-1 was found in patients with HAM (p < 0.001). Furthermore, we found a positive correlation with HAM sICAM-1 and tumor necrosis factor-alpha levels in the sera of patients with multiple sclerosis in the active phase (r = 0.88, p < 0.01) and in those with HAM (r = 0.86, p < 0.01). These results suggest that serum sICAM-1 may be related to clinical activity in patients with multiple sclerosis and the detection of sICAM-1 could be useful as a marker of inflammatory disease.

Adult↗

A patient with early gallbladder cancer derived from a Rokitanski-Aschoff sinus.

We present herein a case of a 40-year-old male with early gallbladder cancer derived from a Rokitanski-Aschoff sinus (RAS). The patient originally presented at our hospital with epigastric discomfort, following which a diagnosis of adenomyomatosis (ADM) of the gallbladder was made, and a cholecystectomy performed. Histopathological examination of the resected specimen revealed a 7-mm well-differentiated papillo-tubular adenocarcinoma in the RAS epithelium in the body of the gallbladder. The RAS extended to the "pm" layer but the adenocarcinoma was an in situ lesion localized within the RAS epithelium. Considering the difficulties in making an early diagnosis of gallbladder cancer, active surgery should be performed for patients in whom ADM is seen in the gallbladder.

Adenocarcinoma, Papillary↗

A case of appendiceal mucocele showing massive mucous production with concomitant colonic cancer.

A 58-year-old male patient presented with abnormal discharge of 200 ml transparent fecal mucus. Irregular protuberance of the ascending colon into the adjacent ileocecal region was observed by colonofiberscopy, and a cystic lesion in the ileocecal region was suggested by computerized axial tomography. Pale yellowish semitransparent jellied substances were observed exudating from the site of ileocecal resection. The diagnosis established was moderately differentiated colonic adenocarcinoma and a mucocele of the appendix. The mucus discharge disappeared after resection. Biochemical analysis of the mucus suggested the mucocele as a source of the discharged mucus. We report an extremely rare case of mucocele of the appendix that may be related to the cause of mucous stool.

Adenocarcinoma↗

Cytotoxicity of T cells for cerebral endothelium in multiple sclerosis.

We investigated the cytotoxic effect of peripheral blood T cells on cerebral endothelium in patients with MS. We examined in vitro the damage to 51Cr-labelled dissociated human brain endothelial cells produced by mitogen-stimulated T cell lines from patients with MS and controls. Endothelial targets were lysed by T-lymphocytes from patients with acute relapsing MS during an exacerbation at every target-effector cell ratio tested compared with controls (P < 0.001). The percentage of endothelial targets lysed was not significantly increased by incubation with T cells from patients with acute relapsing MS in remission and chronic progressive MS, compared with that of normal subjects. Relapsing MS patients during an exacerbation had significantly higher interleukin-1 (IL-1)-alpha concentrations in cultures of targets with effector cells than normal subjects (P < 0.02). Experiments of major histocompatibility complex (MHC)-restricted cytotoxicity in MS demonstrated incomplete blocking of specific lysis by either anti-MHC class I or class II monoclonal antibody (mAb). These results indicate that cytotoxicity of T cells for cerebral endothelial cells may play a role in the initiation of immune response in acute relapsing MS during an exacerbation which appears to cause an increase in blood-brain barrier (BBB) permeability.

Adolescent↗

Anti-lymphocyte antibodies and circulating immune complexes in the sera of patients with myelopathy associated with human T lymphotropic virus type-I.

We measured levels of circulating immune complexes in the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) by Raji cell assay and C1q binding assay using an enzyme-linked immunosorbent assay (ELISA). The levels of anti-lymphocyte antibody were also measured using normal donor peripheral blood T-lymphocytes. The levels of anti-lymphocyte antibodies were significantly higher in the sera of patients with HAM compared to controls (P < 0.01). The concentrations of immune complexes measured by Raji cell assay were also significantly higher in the HAM patients' sera than in controls. However, when levels of immune complexes were measured by C1q binding assay, there was no significant difference between HAM patients and controls. There was no significant difference in the levels of anti-lymphocyte antibodies and immune complexes between HTLV-I carriers and controls. Circulating immune complexes detected by the Raji cell assay did not include HTLV-I p-19 as detected by the indirect immunofluorescent method. Levels of anti-lymphocyte antibody were correlated with levels of circulating immune complexes as detected by the Raji cell assay in the sera of patients with HAM. These findings indicate that anti-lymphocyte antibodies and circulating immune complexes are present in the sera of HAM patients, and that the levels of complexes detected by Raji cell assay may reflect anti-lymphocyte antibody levels.

Adult↗

Bile canalicular contraction is coincident with reorganization of pericanalicular filaments and co-localization of actin and myosin-II.

We examined the relationships between actin-myosin interaction and bile canalicular contraction using a new experimental model: cytoskeleton-enriched canalicular membranes (CCM). In CCM, the bile canaliculus compartment is isolated complete with membrane-attached pericanalicular actin filaments and the surrounding intermediate filament sheath. Immunofluorescence and immunoelectron microscopy showed that actin and myosin-II were distributed over pericanalicular microfilaments that insert into adherens (belt) junctions; intermediate filaments predominantly inserted into desmosomes. The addition of "contraction solution" (1 microM Ca2+, 1 mM ATP) resulted in closure of CCM lumens, which was interpreted as canalicular contraction. Contraction was also associated with shortening and/or twisting of canaliculi. Rearrangement of actin filaments and myosin-II with co-localization of actin and myosin was observed. Evidence is also provided for attachment of actin-myosin-II aggregates to intermediate filaments coincident with contraction, suggesting a key scaffold function for intermediate filaments of the canaliculus. Attention is drawn to the overall similarity of structure-function dynamics in hepatic apical membranes to those described in intestinal brush border membrane preparations. The results are consistent with dynamic actin-myosin interaction with co-localization of actin and myosin-II in filament clumps coincident with canalicular contraction.

Actin Cytoskeleton↗

Increased levels of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor in the cerebrospinal fluid of patients with multiple sclerosis.

We investigated the presence of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble tumor necrosis factor receptor (sTNF-R) antigens in the CSF of patients with multiple sclerosis (MS) using a double-determinant ELISA. Patients with acute relapsing MS during an exacerbation (p < 0.001) and those with chronic progressive MS (p < 0.001) had significantly increased CSF levels of sICAM-1 compared with subjects with other neurologic diseases. CSF levels of sTNF-R were also significantly increased in patients with acute relapsing MS during an exacerbation (p < 0.001) and chronic progressive MS (p < 0.001) compared with subjects with other neurologic diseases. CSF levels of sICAM-1 and sTNF-R were positively correlated in patients with acute relapsing MS during an exacerbation (r = 0.81, p < 0.01) and chronic progressive MS (r = 0.86, p < 0.001). These results suggest that active immune reactions involving ICAM-1 and TNF-R production are present within the CNS and that both sICAM-1 and sTNF-R are important immunologic markers of the clinical activity of MS.

Adolescent↗

Adhesion of cerebral endothelial cells to lymphocytes from patients with multiple sclerosis.

To investigate the factors regulating the entry of lymphocytes into the brain, we assessed the adhesion in vitro of 51Cr labelled lymphocytes from peripheral blood of patients with multiple sclerosis (MS) to human cerebral endothelial cells, and evaluated the effect on the adhesion of endothelium activated by interferon-gamma (IFN-gamma), lipopolysaccharides (LPS), interleukin-1 (IL-1) and tumor necrosis factor (TNF). Patients with acute relapsing MS during an exacerbation showed significant increase in MNC adherence to cerebral endothelial cells as compared with controls (p < 0.001). MNC adherence to cerebral endothelial cells activated by IFN-gamma or LPS, was significantly increased as compared to the controls (p < 0.01). MNC adherence to endothelial cells was not blocked by antibodies against the intercellular adhesion molecule-1 (ICAM-1), but was blocked by lymphocyte function-associated antigen-1 (LFA-1). The increased adherence observed in patients with acute relapsing MS during an exacerbation would modulate the migration of lymphocytes across the blood-brain barrier (BBB).

Adolescent↗

[Effect of intracerebral injections of tumor necrosis factor and interleukin-1].

In order to examine the effect of cytokines on the central nervous system, we injected tumor necrosis factor (TNF) alpha or interleukin-1 (IL-1) alpha into the brains of mice. Although mice injected with saline alone exhibited no inflammatory responses, histopathological studies of mice injected with TNF alpha or IL-1 alpha revealed mild mononuclear cell infiltration around the blood vessels, edema and mild hemorrhage several millimeters distant from the needle track. These findings are similar in pattern to those observed in the early stage of experimental allergic encephalomyelitis (EAE). Increased vascular permeability induced by injections of TNF or IL-1 may play a role in the pathogenesis of these inflammatory responses. The direct cytokine injection model offers a new way of examining the mechanisms of early inflammation in the central nervous system.

Animals↗

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↗

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↗

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↗