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Biomedical subjects

M Tsujihata

Publications and source records attributed to M Tsujihata.

At least 55 records · Page 3Linked to original sources

Characterization of adherent T cells to human endothelial cells in patients with HTLV-I-associated myelopathy.

To clarify the phenomenon of increased adherence of T cells to endothelial cells (EC) in patients with HTLV-I-associated myelopathy (HAM), we determined the surface markers and expression of lymphocyte function antigen-1 (LFA-1) in T cells adherent or nonadherent to EC. The percentage of activated or HLA-DR+ T cells and the expression of LFA-1 in the adherent cell population were significantly higher than those in the nonadherent cell population. Moreover, the CD4 to CD8 ratio of the HLA-DR+ cells in the EC-adherent T cells was significantly higher than that in the nonadherent cells. Collectively, these results indicate that increased adherence of T cells to EC in HAM patients is based on the increase of activated T cells with high density LFA-1 expression in the peripheral blood. Moreover, CD4+ HLA-DR+ cells exhibited more adhesive activity to EC than CD8+ HLA-DR+ cells, suggesting that activated CD4+ cells, rather than activated CD8+ cells, may be important as the first trigger for T cell-infiltration to the central nervous system in the immunopathogenesis of HAM.

Adult↗

Antiproliferative factor against the human glioblastoma cell line T98G identified in culture supernatants of CD4+ cells from patients with HTLV-I-associated myelopathy.

We investigated culture supernatants of peripheral blood mononuclear cells (MNC) derived from patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) for antiproliferative activity against the human glioblastoma cell line T98G. When T98G cells were cultured with condition medium containing culture supernatants of MNC from patients with HAM, the proliferation of T98G cells was significantly suppressed, compared with that of supernatants from HTLV-I seropositive carriers or seronegative controls. To clarify which population of MNC produced the antiproliferative humoral factor for T98G cells, we separated MNC into macrophage-depleted or B cell depleted populations, and further to both CD4+ and CD8+ T cells by using the panning method or plastic adherence. These studies demonstrated that the antiproliferative activity was mediated by a humoral factor produced by T cells, specifically CD4+ cells. This activity was blocked by a neutralizing monoclonal antibody against interferon-gamma (IFN-gamma). Moreover, IFN-gamma levels were elevated in the culture supernatants of CD4+ cells from HAM patients. Thus, the antiproliferative activity against T98G cells is mainly due to IFN-gamma derived from CD4+ cells of patients with HAM.

Adult↗

Production of granulocyte-macrophage colony stimulating factor by human T-lymphotropic virus type I-infected human glioma cells.

We investigated the production of granulocyte-macrophage colony stimulating factor (GM-CSF) by human T-lymphotropic virus type I (HTLV-I)-infected human glioma cells (KG-1-C and T98G). When glioma cells were co-cultured with HTLV-I-producing T cell lines (HCT-1 and MT-2), GM-CSF was detected in the culture supernatant. GM-CSF was produced in all the co-cultures even after several passages. In co-cultures of KG-1-C and HCT-1 cells with Millicell, the amount of GM-CSF produced in the supernatant was almost as low as in the culture of HCT-1 alone. Moreover, for co-cultures of KG-1-C and HCT-1 or MT-2 cells, the production of GM-CSF was significantly suppressed in the presence of IgG from patients with HAM. Double-label immunostaining showed that GM-CSF-producing glioma cells always were stained by a monoclonal antibody against HTLV-I p19, indicating that HTLV-I infection of glioma cells caused GM-CSF production. These data suggest that human glial cells infected with HTLV-I gain the ability to produce cytokines.

Antibodies, Monoclonal↗

Locked-in syndrome and abnormal orientation of the right vertebral artery in a young man.

A 35-year-old man developed a cerebral infarction and experienced transient ischemic attacks originating from the vertebrobasilar artery, as well as locked-in syndrome. He recovered with minimal neurological deficit. On cerebral angiography, the orientation of the right vertebral artery was markedly abnormal as it entered the foramina of the transverse process at the level of the third cervical vertebra. We concluded that the abnormal orientation of the vertebral artery caused the thrombosis and that the transient ischemic attacks, locked-in syndrome and cerebral infarction were brought about by thromboemboli originating in this artery.

Adult↗

[Primary malignant lymphoma of the urinary bladder].

We report 2 cases of primary malignant lymphoma arising in the urinary bladder. The first case was a 64-year-old woman complaining of gross hematuia during the follow-up period of transitional cell carcinoma (grade 2, stage pTa) of the bladder that was treated with TUR in 1989. Her bladder tumor of this time was broad based, not papillary, and situated on the right side wall with bleeding. The pathological diagnosis of transurethral biopsy specimens was non-Hodgkin lymphoma, diffuse large, B cell type. Four courses of CAP chemotherapy was so effective that she has been free of the disease up to now. The second was a 51-year-old woman presenting with painless gross hematuia. A solid, round and intramural tumor, which was recognized on the left side wall by cystoscopy, was resected endoscopically as much as possible. Three courses of VEPA chemotherapy was done because pathologically it was non-Hodgkin lymphoma, diffuse medium, B cell type, although no evidence of other tumors in any organs was fortunately detected with further examinations. She has been doing well without recurrence for 9 months after discharge from the hospital. Primary malignant lymphoma of the bladder is unusual. About 70 cases have been reported in foreign countries, but only 23 cases in Japan. When malignant lymphoma is confined to the bladder, radiation and chemotherapy can be curative, and yet preserve the function of the bladder.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical evaluations of tumor enucleation for incidental renal cell carcinoma].

We performed tumor enucleation in 21 patients of renal tumors from Jan. 1980 to Feb. 1993. Of them 19 had renal cell carcinoma. We reviewed the results of clinical experiences. Preoperatively, all patient underwent ultrasound, computerized tomography (CT) and angiography, and evaluated tumor characteristics in terms of its localization, size and pre or absence of pseudocapsule. All cases were shown to be well encapsulated. Of them 17 were asymptomatic and detected incidentally, whereas remaining one case was bilateral renal cell carcinoma clinically characterized by gross hematuria. This case was treated by radical nephrectomy on the right side and enucleation of the tumor on the left side. All cases had localized renal cell carcinoma (stage 1) of low grade (15 cases of grade 1 and 3 of grade 2), and the diameter of the tumor averaged 3.4 cm. Of 18 cases 2 died, one died of causes unrelated to RCC and the other of the metastasis of bilateral RCC after nephrectomy. The 16 cases are presently free of disease for maximal follow up period of 92 months. We consider that tumor enucleation will be indicated for tumors found incidentally, surrounded by pseudocapsule, of small size (less than 3.0 cm in diameter), and of low grade and low stage, and that tumor enucleation for renal cell carcinoma could be curative yet preserve renal function in selected patients.

Adult↗

[Anti-voltage-gated calcium channel antibodies in the Lambert-Eaton myasthenic syndrome].

We have tested 29 patients with the Lambert-Eaton myasthenic syndrome (LEMS) for serum antibodies to voltage-gated calcium channels (VGCC) using an immunoprecipitation assay in which [125]-omega-conotoxin GVIA is used to label calcium channels extracted from IMR-32, a human neuroblastoma cell line. Fifty-five percent of these patients had significant levels of antibody [31.6 (26.5, 48.2) (med., Q1, Q3) pmol/L, n = 29], compared with healthy controls [21.5 +/- 3.4 (mean +/- SD) pmol/L, n = 30] and other neurological disorders [25.2 +/- 4.2 (mean +/- SD) pmol/L, n = 10]. These antibodies were found in 43% of the patients with small cell lung carcinoma (SCLC) without signs and symptoms of LEMS [32.2 +/- 7.2 (mean +/- SD) pmol/L n = 30] and 7% of the myasthenic patients [21.4 +/- 6.8 (mean +/- SD) pmol/L n = 14]. Anti-VGCC antibody titers did not correlate with presence of SCLC, disease duration, or an electromyographic index of disease severity. Our results suggest that the antibodies detected in this assay are specific to some patients with LEMS, but not all. This assay is a useful aid in diagnosing LEMS but has much room for improvement.

Adult↗

[Asymptomatic pheochromocytoma: a report of three cases].

We present three cases of asymptomatic pheochromocytoma treated at Sumitomo Hospital. They had no hypertensive episode. The tumors of Case 1 and Case 3 were incidentally detected by abdominal ultrasonography at the Health Screening Center of Sumitomo Hospital. The tumor of Case 2 was incidentally detected by abdominal ultrasonography in the health examination of his company. Case 1. A 49-year-old male was hospitalized in Apr. 1992 because of further examination of a right adrenal mass. He underwent right adrenalectomy and its histological examination revealed pheochromocytoma. Case 2. A 45-year-old male was referred to our department for further examination of a left adrenal mass in Aug. 1993. On admission, endocrinological examination was almost normal. He underwent surgical removal of the tumor and its histological examination revealed pheochromocytoma. During the operation, blood pressure and pulse rate were almost unchanged. Case 3. A 51-year-old female was hospitalized in Oct. 1993 because of further examination of a left retroperitoneal mass. She underwent surgical removal of the tumor and its histological examination showed paraganglioma.

Adrenal Gland Neoplasms↗

[Bilateral adrenal myelolipoma: a case report].

A case of bilateral adrenal myelolipoma is presented. The patient was a 40-year-old man in whom a retroperitoneal tumor was unexpectedly found by ultrasonography. Computed tomography revealed bilateral adrenal masses, 14.0 cm in diameter on the right side, and 5.0 cm on the left side, with heterogeneous low density components. Magnetic resonance imaging also revealed a high intensity mass with heterogeneity. Laboratory examination of adrenal function revealed normal results. We confirmed myelolipoma of bilateral adrenal gland, and performed right adrenalectomy, and left tumor enucleation. The right tumor was 14.0 x 12.5 x 10.0 cm in size and 920 g in weight, and the left tumor 5.0 x 4.5 x 4.0 cm in size and 50 g in weight. Pathology disclosed an admixture of mature adipose tissue and hematopoietic elements resembling bone marrow. Histopathological diagnosis was adrenal myelolipoma. This case was the 6th to be reported in the Japanese literature as bilateral adrenal myelolipoma.

Adrenal Gland Neoplasms↗

[A case of cerebral venous sinus thrombosis occurring in ulcerative colitis].

A 33-year-old man with a 13-year history of ulcerative colitis developed generalized clonic convulsions after transient right hemiparesis. A computed tomographic scan revealed a hemorrhagic lesion in the left frontal lobe and contrast tomography demonstrated delta-sign in the occipital area. A sagittal gadolinium-contrast magnetic resonance imaging scan demonstrated a low signal intensity area in the superior sagittal sinus. The venous phase of his carotid angiogram showed a lack of filling of the superior sagittal sinus. Coagulation studies revealed abnormal findings, elevated fibrinogen and increased aggregation of platelets. Cerebral venous or sagittal thrombosis occurring in ulcerative colitis is very rare in Japan. But thromboembolism is known as one of the extraintestinal complications of ulcerative colitis, and a hypercoagulable state may occur even in the inactive state. Ulcerative colitis should be considered as one of the etiologies of thromboembolism in addition to the results of coagulation studies for the prevention of cerebrovascular diseases.

Adult↗

[A 46-year-old woman with myasthenia gravis associated with macromastia, erythroderma and hypogeusia].

A 46-year-old woman developed blepharoptosis, diplopia and hypogeusia in 1984, and was diagnosed as having myasthenia gravis and malignant thymoma. Her symptoms improved by thymectomy and oral prednisolone administration. In 1988 she complained of breast pain and swelling during menstruation. In 1990 her breast was enlarged to the size of an adult head, and she developed erythroderma and hypogeusia. She was admitted to Nagasaki University Hospital in August, 1990. On admission, erythema was seen in the whole body especially in the face, anterior chest, abdomen and the thigh. Her breast was the size of an adult head. Muscle strength was weak, and ocular movement was limited. She had blepharoptosis. Papillae of the tongue were atrophic. Endoclinological investigations revealed an elevation of PRL to 14.6 ng/ml (normal < 10), antibodies to the acetylcholine receptor to 118.0 nM (normal < 0.5). In TRH stimulation test the response of PRL was amplified. Four intrathoracic masses suspected of recurrence of malignant thymoma were seen in CT. Her macromastia depended upon the amount of PRL, and was reduced by bromocriptine. Erythroderma and hypogeusia were relieved by plasmaphersis. Therefore autoimmune mechanism may be related to these symptoms.

Breast↗

[Report of a case of small cell lung cancer associated with Lambert-Eaton myasthenic syndrome and subacute cerebellar degeneration--with a review of the Japanese literature].

We report a patient with small cell lung cancer associated with Lambert-Eaton myasthenic syndrome (LEMS) and subacute cerebellar degeneration (SCD). The patient was a 71-year-old man suffering from weakness of the limbs and a gait disturbance who developed limb ataxia and dysarthria one month after admission. Electrophysiologic studies confirmed the diagnosis of Lambert-Eaton myasthenic syndrome. Chest X-rays 2 months after admission revealed an abnormal shadow, and small cell lung cancer was diagnosed on the basis of biopsy specimens. Anti-voltage-gated calcium channel antibody was positive. Anti-Yo and -Hu antibodies were negative. The patient was treated by plasmapheresis and chemotherapy, which resulted in a transient improvement in the LEMS symptoms but not in the SCD. Fifteen cases of LEMS associated with SCD have been reported in the Japanese literature, and all were accompanied by small cell lung cancer. We discuss the frequency of association with LEMS and SCD and the effects of plasmapheresis and chemotherapy in both diseases.

Aged↗

[A case of superficial hemosiderosis of the central nervous system with normal CSF findings and unknown source of bleeding].

A 65-year-old woman had suffered from slowly progressive hearing loss for one year. She had neither repeated episodes of headache or vomiting nor a past history of neurosurgical operation. Neurologic examination revealed moderate diminution in hearing, pyramidal tract sign and cerebellar ataxia without dementia. CSF was under normal pressure, clear and colorless, with total protein 35 mg/dl, glucose 59 mg/dl and a cell count of 2 WBC/mm3. T2-weighted images (TR200/TE80) of high-field MRI demonstrated marginal hypointensity of the brainstem, the Sylvian fissures and the entire spinal cord. Angiography of the cerebral vessels failed to identify the source of bleeding. To our knowledge, this is the first report of superficial hemosiderosis of the central nervous system with normal CSF findings and an unknown source of bleeding confirmed by MRI.

Aged↗

Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with defective heparin binding associated with thrombosis.

A novel variant of antithrombin III (AT III) that lacks affinity for heparin was found in a 33-year-old man who suffered from recurrent cerebral infarction. The propositus had a history of recurrent ischemic attacks from the age of 28. He was obese and had a smoking habit (30 to 40 cigarettes/day), low high-density lipoprotein cholesterol, and a mild glucose intolerance as the possible risk factors for thrombosis. No family history of thromboembolic episodes was observed. Coagulation studies found low heparin cofactor activity (55%) of AT III, with a normal immunoreactive level (109.7%) and progressive antithrombin activity (117%). Other factors capable of predisposing him to hereditary thrombophilia were within normal ranges. Analysis by crossed immunoelectrophoresis in the presence of heparin and affinity chromatography on heparin-Sepharose demonstrated that the propositus' AT III was composed of two populations, one having no affinity for heparin and the other binding heparin normally. Nucleotide sequencing of 7 exons of the propositus' AT III gene using polymerase chain reaction and subcloning disclosed a transition of thymine to cytosine in exon 3a (codon 116) of the AT III gene leading to a Ser116-Pro conversion. Allele-specific oligonucleotide hybridization procedures confirmed the presence of the mutation in the propositus' genomic DNA. Using the same technique, the mutation was also found in his father's genomic DNA, but not in that of his mother. These findings indicate that Ser116 is an important amino acid residue in heparin binding and that the propositus is heterozygous for the abnormality. Furthermore, the fact that the propositus suffered from recurrent cerebral infarction suggested that being heterozygous for a heparin-binding defect would lead to a predisposition to thrombosis when associated with various risk factors. The name AT III Nagasaki is proposed for this variant AT III containing a novel Ser116-Pro mutation.

Adult↗

Effect of myasthenic IgG on degradation of junctional acetylcholine receptor.

We investigated the effect of the IgG from patients with myasthenia gravis (MG) on the degradation of normal rat junctional acetylcholine receptor (AChR) labeled with 125I-alpha-bungarotoxin (BuTx) and calculated the degradation rate (DR). The DR for the IgG from these patients was significantly higher than that from healthy volunteers and patients with other autoimmune diseases. For MG, DR was significantly correlated with the severity of the disease but not with anti-AChR antibody titer. DR was accelerated by IgG from patients with generalized MG whose antibody titers were in the normal range and by IgG from patients with ocular MG. These results indicate that measurement of the DR of junctional AChR in normal rats is more closely correlated with the severity of the disease than is measurement of anti-AChR antibody and that the former is a sensitive and confirmatory method for evaluating MG.

Adolescent↗

Heparin treatment in patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy: a preliminary study.

Ten patients with HTLV-I-associated myelopathy (HAM) were treated in an uncontrolled preliminary trial of heparin. In 7 patients, motor dysfunction improved substantially and the effect continued for more than a month after the discontinuation of therapy. Sensory and urinary disturbances also improved in 3 of 4 and in 2 of 10 patients, respectively. Heparin did not alter the subsets of peripheral blood lymphocytes nor the titers of anti-HTLV-I antibodies in serum and cerebrospinal fluid. Spontaneous proliferation of peripheral blood lymphocytes, however, was depressed significantly (P < 0.05) in all cases. Heparin therapy has some advantages in cost, ease of administration and fewer side effects compared to other therapies such as plasmapheresis and interferon-alpha. We conclude that heparin can be administered safely to HAM, and that a double-blind placebo-controlled trial is warranted to determine its efficacy in HAM.

Adult↗

Circadian rhythms of blood pressure and heart rate in patients with human T-lymphotropic virus type-I-associated myelopathy.

Noninvasive ambulatory blood pressure and heart rate monitoring were used to investigate cardiovascular dysfunction in patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The subjects were 23 patients with HAM, and 23 sex- and age-matched normotensive healthy volunteers (controls). Circadian rhythms of blood pressure and heart rate were present in both the HAM patients and controls. Amplitudes and the 24-hr mean systolic and diastolic blood pressures were significantly lower in the patients than in the controls. The 24 hr mean heart rate was significantly higher in the patients, the difference being particularly marked during the night. Differences in the acrophases of the systolic and diastolic blood pressures and heart rate between patients and controls were small but still significant. These results suggest that subclinical cardiovascular autonomic dysfunction is present in HAM patients.

Adult↗

Treatment of myasthenia gravis: a comparison of the natural course and current therapies.

Ninety-five patients with generalized myasthenia gravis were followed for 10 years to evaluate the long term effects of prednisolone, thymectomy, or both, and they were compared with a group only with anticholinesterase treatment. Only 15.0% of the patients with anticholinesterase alone had showed improvement 10 years after the onset, but more than 60% of those treated with prednisolone, thymectomy, or both showed improvement. Especially thymectomy induced complete remissions at 10 years after surgery in more than 20% of the patients. There was no difference between the histology of the thymi and clinical severity, or anti-acetylcholine receptor (AChR) antibody titer. In patients who showed improvement classified "good" of higher 10 years after thymectomy with or without prednisolone, anti-AChR antibody titers swiftly decreased to 37.8% of the value before surgery, and remained low thereafter. This result suggests that the marked decrease in anti-AChR antibody titers within 1 month after thymectomy is a favorable prognostic sign in myasthenia gravis patients who have undergone thymectomy.

Adolescent↗