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Biomedical subjects

K Uozumi

Publications and source records attributed to K Uozumi.

At least 37 records · Page 2Linked to original sources

Serum dehydroepiandrosterone and DHEA-sulfate in patients with adult T-cell leukemia and human T-lymphotropic virus type I carriers.

The serum levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were determined by radioimmunoassay in 38 patients with adult T-cell leukemia (ATL). Levels of serum DHEA and DHEA-S were also measured in 60 human T-lymphotropic virus type I (HTLV-I) carriers, and did not differ from those in 60 healthy control subjects. Serum levels in patients with ATL were lower than those in the age- and sex-matched healthy controls and in HTLV-I carriers with statistical significance. Serum DHEA and DHEA-S in male patients with acute and lymphoma-type ATL were 1.06 +/- 0.77 ng/ml and 245.8 +/- 192.9 ng/ml, respectively. Levels in male patients with chronic and smoldering-type ATL were 1.69 +/- 0.68 ng/ml and 477.6 +/- 251.5 ng/ml, respectively. Serum levels of DHEA and DHEA-S in patients with acute and lymphoma-type ATL were significantly lower than those in patients with chronic and smoldering-type ATL (P < 0.05). These data suggest that a decrease in serum levels of DHEA and DHEA-S may be associated with patients who have some clinical subtypes of ATL. Moreover, androgens may have a therapeutic role in patients with ATL, as administered in patients with hairy-cell leukemia. Because there is at present no curative chemotherapy for ATL, a trial combination of androgens and standard chemotherapy may be a reasonable therapeutic option in such patients.

Adrenal Cortex↗

[Adult T-cell leukemia complicated with intestinal tuberculosis].

We report a patient with adult T-cell leukemia (ATL) complicated with intestinal tuberculosis. A 57-year old man was admitted to our hospital because of fever and dyspnea. He was diagnosed as ATL by leukocytosis [leukocyte count 18,200/microliters with 56% of abnormal lymphocytes which express CD4(+) and CD25(+)] and seropositive result of anti-HTLV-1 antibody. Combination chemotherapy for ATL improved his serum LDH level and peripheral lymph nodes, but fever was still persistent. He had an emergency operation because of perforation of the cecum during the chemotherapy. Histological examination of the resected cecum revealed caseous necrosis and numerous mycobacterium, which induced a diagnosis of intestinal tuberculosis. Although there have been several reports on pulmonary tuberculosis in patients with ATL, this is the first report of intestinal tuberculosis in ATL as far as we know. We conclude that if the patients with ATL have persistent fever of unknown origin, we should take account of intestinal tuberculosis as one of differential diagnosis.

Fever of Unknown Origin↗

Expression of the intestinal T-lymphocyte-associated-molecule recognized by the HML-1 antibody on mononuclear cells from HTLV-I-infected subjects.

We investigated the expression of a monoclonal antibody (HML-1) defined antigen that appears on human intestinal T-lymphocytes in HTLV-I-related disease. We studied 25 ATL, and 24 healthy HTLV-I carriers. Patients with acute ATL showed a variety of the expression of the HML-1 antigen (range 0.4-74.8%). HML-1 expression on mononuclear cells (MNCs) in blood from patients with chronic ATL ranged from 1.7-43.6% (mean 13.5%). This level of expression was less than that of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of patients with acute ATL, but not significantly. In patients with smoldering ATL, the degree of expression ranged from 1.6-13.3% (mean 8.0%). In contrast to patients with acute ATL, MNCs from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and B-cell type chronic lymphocytic leukemia (B-CLL) did not express the HML-1 antigen, except for the 2 patients with ALL. Healthy HTLV-I carriers and healthy controls also were negative for HML-1 reactivity. In acute ATL, patients with gastrointestinal tract infiltration tended to have high expression of the HML-1 epitope. After stimulation with phytohemagglutinin (PHA), healthy HTLV-I carriers showed significantly increased expression of the HML-1 epitope (P < 0.05). Recently, the beta 7 integrin family has been found to play a specific role in mucosal localization or adhesion, and HML-1 protein was found to match the deduced beta 7 N-terminal sequence. We propose that the cellular gene responsible for HML-1 epitope expression may, like IL-2, IL-2R, etc., be transactivated by infection with HTLV-I, and HML-1 antigen gene expression by HTLV-I infection may lead to infiltration of ATL cells with highly expressed HML-1 epitope into the gut mucosa.

Antigens, Neoplasm↗

An adult diagnosed as hyper-IgM immunodeficiency syndrome.

A 27-year-old male who visited our hospital because of pneumonia was diagnosed as hyper-IgM immunodeficiency syndrome. His serum IgM level was markedly elevated, while the serum level of IgD was normal with a markedly decreased level of serum IgG and IgA. The proportion of T and B cells of peripheral blood lymphocytes was normal. However, B cells bearing surface IgG or IgA were not detectable by immunofluorescence technique. There was a consanguineous marriage in his family, suggesting that his disorder was caused by a genetic abnormality such as X-linked recessive and also autosomal recessive inheritance, although further study is necessary. CD40 ligand cDNA did not appear to contain any abnormal changes within the coding region.

Adult↗

Combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) for the acute or lymphoma type adult T-cell leukemia.

43 patients with the acute or lymphoma type ATL were treated with the new combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) between January 1989 and December 1991. Complete response (CR) and partial response (PR) were achieved in 20.9% and 65.1% of all treated patients respectively. The median duration of survival was 6.0 months. The survival duration of patients with a high serum lactate dehydrogenase (LDH) value (> or = 1,000 unit) and/or a poor performance status (PS) (PS 3 or 4) were also improved but not in patients with a severe leukocytosis (> or = 35,000/microliters). Toxicity was mild (grade 1 or 2) except hematologic toxicity in 4 patients (9.3%) and alopecia in one patient (2.3%). In spite of many patients with a poor PS (PS 3 or 4), our chemotherapeutic results are equal or superior to other previous reports. It seems that response-oriented chemotherapy is suitable for the ATL patients with poor prognostic factors. These results indicate that the RCM protocol is very useful as the first choice chemotherapy for the acute or lymphoma type ATL.

Adult↗

Significance of elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukemia.

Although it has been recognized previously that several markers are present in the cerebrospinal fluid (CSF), their clinical usefulness of these markers in the diagnosis of malignant lymphoma infiltrating to the CNS has not yet been established. In order to determine their diagnostic usefulness as markers of meningeal infiltration by lymphoma cells in patients with adult T-cell leukemia (ATL), we measured some soluble factors in the CSF of patients with ATL and non-ATL patients. Soluble CD4 (sCD4) was highly elevated in all patients with ATL and meningeal infiltration. The CSF level of the soluble interleukin-2 receptor (sIL-2R; sCD25) was markedly elevated in 13 (72.2%) of 18 patients with ATL and meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of patients with ATL and meningeal infiltration were significantly higher than in non-ATL patients (p < .01 and p < .001, respectively). These findings indicate that levels of sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration by leukemia cells expressing CD4 and CD25 on surface membranes. CSF levels of sCD4 in 14 (60.9%) of 23 ATL patients and sCD25 in 13 (72.2%) of 18 ATL patients without meningeal infiltration were moderately elevated. These findings suggest that a small number of leukemic cells which were not detected by conventional CSF examination may have infiltrated the meninges in these patients. Sequential measurements of sCD4 and sCD25 in CSF obtained from patients with meningeal infiltration by leukemic cells showed that sCD4 and sCD25 levels reflected the activity of leukemic meningitis and correlated with the number of cells in CSF. However, the levels of sCD4 in CSF did not fall below the limit of detection even when the number of cells in CSF became normal. It is thought that the level of sCD4 in CSF is a more sensitive marker for detecting the infiltration of leukemic cells in CSF than the number of cells present in the CSF considering the clinical course of two patients with acute type ATL. Therefore, ATL patients with meningeal infiltration should receive treatments until sCD4 levels become normal and not just until the number of cells become normal. Our results also suggest that measurement of CSF levels of sCD4 and sCD25 is useful for the differential diagnosis of aseptic meningitis and meningeal infiltration by leukemic cells in patients with smoldering ATL. We conclude that measurement of soluble factors in CSF plays an important role in diagnosis, prophylaxis and treatment of meningitis in patients with ATL.

Biomarkers, Tumor↗

[Double cancer in patients with adult T cell leukemia].

We have studied the incidence and characteristics of associated neoplasms in 210 ATL patients. Twelve patients had other primary neoplasms and the incidence of double cancer was 5.7%. The additional malignancies in ATL patients consisted of 4 cases of stomach, 3 cases of colon and one of each lung, ovary, uterus, liver and bladder cancer. In metachronous double cancer patients, the neoplasm was found before the time of diagnosis of ATL in 5 out of 6 patients. Immunodeficiency due to HTLV-I infection as well as chemotherapy for the preceding neoplasm are suggested to be related to the leukemogenesis of ATL.

Aged↗

Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T-cell leukemia.

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T-cell leukemia (ATL) and other malignant and non-malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 +/- 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 +/- 9.2 U/ml). Non-ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 +/- 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 +/- 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL.

CD4 Antigens↗

Expression of fos proto-oncogene product by monoclonal antibody FO-120 in smouldering adult T-cell leukaemia (ATL).

We investigated the expression of c-fos gene product in peripheral blood mononuclear cells of patients with smouldering adult T-cell leukaemia (ATL) and healthy human T-lymphotropic virus type-I (HTLV-I) carriers by an immunofluorescence assay, using a mouse monoclonal antibody (FO-120) specific for fos gene product. Peripheral blood mononuclear cells derived from healthy HTLV-I carriers were rarely positive for FO-120, less than 2% of the cells weakly reacted with FO-120, whereas positive cells were detected in more than about 10% of cells from patients with smouldering ATL. FO-120 appears to be a useful tool for detecting smouldering ATL in asymptomatic HTLV-I infected people without using molecular techniques.

Adult↗

Elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T-cell leukaemia complicated with meningeal infiltration.

We measured some soluble factors in the cerebrospinal fluid (CSF) of patients with adult T-cell leukaemia (ATL) complicated with meningeal infiltration. Interleukin-4 (IL-4) was not detectable in the CSF of all cases with meningeal infiltration. Interleukin-6 (IL-6) was detected in a few patients with ATL. Measurement of IL-4 and IL-6 in CSF had no diagnostic value for meningeal infiltration of ATL cells. Soluble CD4 (sCD4) was highly elevated in all ATL patients with meningeal infiltration. Soluble interleukin-2 receptor (sIL-2R; sCD25) in CSF was markedly elevated in 13/18 ATL patients (72.2%) with meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of ATL patients with central nervous system (CNS) symptoms were significantly higher than those of non-ATL patients with CNS symptoms. These observations indicate that sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration of leukaemia cells that expressed CD4 and CD25 on the surface membrane and new markers for the meningeal infiltration of ATL cells.

CD4 Antigens↗

[Oral administration of low-dose etoposide for maintenance chemotherapy in adult T cell leukemia patients].

We studied the effectiveness of low-dose, oral administration of etoposide for maintenance chemotherapy of patients with adult T cell leukemia (ATL). Sixteen patients (9 males and 7 females) in remission (9 in complete remission and 7 partial remission) were orally administered 25 or 50 mg/day of etoposide. Median response duration of all the patients to the therapy was 18.6 months, ranging from 5.0 to 34.0 months. Thirteen out of the 16 patients relapsed, and 9 of them died of tumor progression. Appetite loss occurred in one case, without any other severe side effects. It has been suggested, therefore, that oral administration of the etoposide is useful for maintenance chemotherapy in ATL patients.

Administration, Oral↗

[Adult T-cell leukemia with Ki-1 expression].

A 64-year-old man was admitted to our hospital complaining of fever and edema in February, 1990. Lymph node biopsy revealed diffuse lymphoma pleomorphic type according to the LSG classification. On hematological examination, leukocyte count was 23,500/microliters, of which 36% abnormal lymphocytes expressing CD2, CD3, CD4 and CD25 as same as the lymph node cells. Anti-HTLV-I antibody in serum was positive. From these data, the diagnosis of adult T-cell leukemia (ATL) was made. ATL cells in the blood and lymph node expressed CD30 (Ki-1). CD30 positive ATL cells derived from the blood was increased after short-term culture. The induction of Ki-1 antigen in cell lines and short-term cultured cells from ATL patients was accompanied by the appearance of the HTLV-I related antigen. Then, we suggest that there was some relation between expression of the Ki-1 antigen and activation by HTLV-I in ATL cells.

Antigens, CD↗

[Endoscopic analysis of gastric mucosal lesions in patients with adult T-cell leukemia during chemotherapy].

Gastric mucosal lesions in 13 patients with adult T-cell leukemia (ATL) were endoscopically studied at least at 2 occasions during chemotherapy for these patients. X-ray examinations by using barium meal showed deformities in 10 patients and abnormal mucosal pattern in 11 out of 13 patients with ATL. The endoscopic examinations revealed gastric ulcers in 5 patients, erosion in 8, diffuse bleeding in 2, tumorous mucosal folds in one, and submucosal tumor in one patient. In 9 out of 12 ATL patients, pathological study revealed that ATL cells had invaded the mucosal area of the stomach. The ulcers and erosions were improved by chemotherapy in 3 out of 5 and 5 out of 8 patients, respectively, whereas the erosion was not reduced in 2 and even aggravated in one patient. Interestingly, the gastric lesions formed by ATL cell invasion were improved by the administration of anticancer agents in 5 out of 9 patients. However, these lesions reappeared together with systemic lesions of ATL.

Adult↗

[Cyclic thrombocytopenia with chronic thyroiditis and ankylosing spondylitis].

A 58-year-old man with cyclic thrombocytopenia who was initially diagnosed as idiopathic thrombocytopenic purpura (ITP), concomitant with chronic thyroiditis and ankylosing spondylitis, was reported. Serum level of T 3 (0.48 ng/ml) and T 4 (2.1 micrograms/ml) were both subnormal and that of TSH (257.1 microU/ml) was markedly elevated. Thyroid test (6400X) and microsome test (6400X) was both positive, but anti-nuclear antibodies were negative. Radiographic findings of lumbar spine showed the typical "bamboo spine" and HLA B 27 was positive. Therapies for ITP, such as adrenocorticosteroids including steroid pulse therapy, high-dose intravenous gamma-globulin, danazol, slow infusion of vinca alkaloids and splenectomy, were only effective transiently. After these therapies platelet counts began to fluctuate from 0.4 X 10(10)/L to 34.4 X 10(10/L, therefore the diagnosis of cyclic thrombocytopenia was done. Interestingly low-dose methotrexate (MTX) was effective, and the cyclic fluctuation of platelet counts disappeared. These observations in this case were very suggestive of the pathogenesis of cyclic thrombocytopenia and mechanisms of cyclic change of platelet counts.

Humans↗

[Surface phenotypic diversity of CD4 or CD8 in ATL].

A 51-year-old woman was admitted to our hospital complaining of lymphadenopathy in June, 1987. Lymph node biopsy revealed diffuse lymphoma, mixed cell type according to the LSG classification. On hematological examinations, leukocyte has counted 12,400/microliters, of which 15% abnormal lymphocytes containing human T cell lymphotropic virus type-1 (HTLV-1) proviral DNA into the cellular DNA. She was diagnosed as adult T-cell leukemia (ATL). The abnormal lymphocytes in the peripheral blood expressed CD4 but lymph node cells expressed CD8. Thirty months after initial diagnosis, abnormal lymphocytes began to increased and reached 30,500/microliters. Surface phenotype of abnormal lymphocytes changed CD3+ CD4+ CD8- OKla1+ to CD3- CD4- CD8- OKla1-. This change is considered to show the surface phenotypic diversity in ATL cells.

Antigens, Differentiation, T-Lymphocyte↗

Expression of P-glycoprotein in adult T-cell leukemia cells.

We have examined the expression of P-glycoprotein (P-gp) in adult T-cell leukemia (ATL) samples from 25 patients. Based on immunoblotting with a monoclonal antibody against P-gp, C219, 8 of 20 ATL patients were P-gp positive at the initial presentation. All 6 patients at the relapsed stage were P-gp positive, and refractory to chemotherapy. The expression of MDR1 mRNA in P-gp-positive ATL cells was increased at the relapsed stage of one patient. P-gp of this patient was photolabeled with [3H]azidopine and the labeling was inhibited with nimodipine, vinblastine and progesterone. These results suggest that P-gp expressed in ATL cells from patients at relapsed stage has the same binding site(s) for the drugs as that in multidrug resistant cells, and is correlated with the refractory nature of the cells to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗