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Biomedical subjects

M Tara

Publications and source records attributed to M Tara.

At least 19 recordsLinked to original sources

Urinary excretion of parathyroid hormone-related protein as a predictor of hypercalcemia in patients with adult T-cell leukemia.

Hypercalcemia with adult T-cell leukemia (ATL) is chiefly caused by an excessive production by tumor cells of parathyroid hormone-related protein (PTHrP). We have previously reported hypercalcemic patients with solid tumors to excrete a large amount of the C-terminal fragments of PTHrP (C-PTHrP) into their urine. To elucidate whether PTHrP production correlates with or predicts the development of hypercalcemia, we studied the urinary excretion of C-PTHrP in 36 ATL patients. The urinary excretion of C-PTHrP was in the normal range (< 0.40 nmol equivalent to PTHrP (109-141)/g creatinine) in HTLV-1-positive carriers (n 3), ATL patients in complete remission (n 2) and chronic type ATL patients (n 2). It was marginally increased in seven patients in partial remission, and gradually increased as the disease progressed. In 20 patients who died without or with hypercalcemia, it was increased to 1.98 +/- 0.69 (n 9) and 7.6 +/- 2.1 nmol/g creatinine (mean +/- SD, n 11, P < 0.01), respectively. Urinary C-PTHrP excretion was significantly correlated with serum calcium and LDH levels as well as with CD25-positive cells in the peripheral blood. In four patients whose urinary excretion had been serially determined, it increased prior to the development of hypercalcemia. The findings suggest the urinary excretion of C-PTHrP to be of use as a predictor of the development of hypercalcemia in ATL patients. In ATL patients whose urinary excretion of C-PTHrP is progressively increasing, the serum calcium concentration should be carefully monitored to prevent hypercalcemic crisis.

Adult

[A study on the frequency of von Willebrand factor deficiency state].

In order to elucidate the prevalence of von Willebrand factor (vWF) deficiency state, we investigated plasma vWF levels among 343 patients with bleeding tendency, 465 patients without bleeding tendency and 704 random unrelated normals living in Kagoshima prefecture. The prevalence of symptomatic vWF deficiency state was at least 2.3 per 100,000 of the population, and that of asymptomatic one in healthy individuals was 1.3%. These results indicate that the overall incidence of vWF deficient state in general population would be considerably higher than that previously reported.

Adolescent

[Plasma concentrations of plasminogen activator inhibitor 2 in patients with hematological malignancies and their clinical significance].

We investigated plasma levels of plasminogen activator inhibitor 2 (PAI-2) in 40 patients with hematological malignancies including acute leukemia, chronic leukemia, hemophagocytic histiocytosis (HH) and histiocytic sarcoma (HS). The plasma PAI-2 levels in the patients with mononuclear phagocyte system (MPS) proliferative disorders (M4, M5, and CMMoL on FAB classification, HH and HS) were all above the cut-off value in healthy subjects. In a patient of reactive HH, there was a close correlation between Plasma PAI-2 and serum ferritin levels during the clinical course. These results indicate that the increase of plasma PAI-2 would be a diagnostic indicator of MPS proliferative disorders.

Adult

[Clinical characteristics of anti-phospholipid antibodies].

Twenty-one patients with anti-phospholipid antibodies (APLA), who were selected from 104 patients with antinuclear antibody or anti-DNA antibody, were studied to define clinical characteristics of APLA. Of the 21 patients, the incidences of IgG anti-cardiolipin antibody (ACA), IgM ACA, lupus anticoagulant (LAC) and BFP-STS were 20, 7, 11 and 12, respectively, and they were highly related with each other. The number of items of the 1982 ARA revised criteria for the classification of SLE was significantly low (mean value = 3.3), and also the level of serum C 4 was significantly high (mean value = 88% of normal) compared with those in patients without APLA. The incidence of thrombocytopenia and hemolysis was significantly high when compared with those in patients without APLA, and they were closely related to the presence of LAC. The incidence of thrombosis was markedly high (48%), 10 of 21 patients, especially those of cerebral infarction and deep vein thrombosis. Cerebral infarction was significantly associated with LAC. The obstetric complication was 4 of 13 patients (31%) in the incidence, which was significantly high compared with that in patients without APLA. Of them, natural abortion was closely associated with LAC. Based on these observations, it seems that autoimmunological disease activity in patients with APLA may be slight to mild, and strongly suggested that APLA may play an important role particularly in the pathogenesis of acquired thrombotic tendency.

Adolescent

[Pure red cell aplasia with monoclonal gammopathy and von Willebrand disease].

We report a case of pure red cell aplasia (PRCA) with benign monoclonal gammopathy (BMG) of IgA.lambda type and type I von Willebrand disease (vWD). A 61-year-old female patient was treated initially with prednisolone, azathioprine and cyclophosphamide with transient and unsatisfactory reticulocyte response. Oral administration of 200 mg of cyclosporine A (CyA)/day was started from July, 1987. A rapid and marked reticulocytosis was seen from a week later and there was a rapid increase in hemoglobin levels, and remission has been maintained for over 22 months. Patient's serum and IgA taken on admission did not show inhibitory activity to both CFU-E growth from her own bone marrow cells obtained in remission and von Willebrand factor. T cell-mediated suppression to CFU-E growth was detected. On family study, the patient's second son was found to be a type I vWD. These results indicate that there is no direct causal relationships between BMG and PRCA or vWD, and that CyA may have a place in the management of PRCA.

Cyclosporins

[Effects of danazol on plasma levels of protein S C4b-binding protein].

In order to elucidate the response of protein S (PS) and C4b-binding protein (C4bp) to danazol, we investigated the serial changes in plasma levels of PS and C4bp during danazol administration in 4 patients with endometriosis. Both total and free PS levels were significantly increased at the time of 2 to 3 weeks after danazol administration as compared to the pretreatment values, while C4bp levels were not changed at all. These results imply that danazol administration to PS deficiency would produce a significant increase in the basal level of free PS, suggesting a potential adjunct to anticoagulant treatment in PS deficiency.

Adult

[Fetal survival after the corticosteroid and low-dose aspirin regimen in a case of anti-phospholipid antibody syndrome].

A 27-year-old woman with anti-phospholipid antibody syndrome, whose first pregnancy had ended in intrauterine fetal death, was treated with prednisolone 0.6 mg/kg/day before second pregnancy. Suppression of anti-cardiolipin antibody activity was rapidly achieved and maintained during the pregnancy. After conception, low-dose aspirin 81 mg/day was started and continued until delivery. She gave birth to a normal live infant with natural full-term delivery. It is strongly suggested that the corticosteroid and low-dose aspirin regimen can lead to successful pregnancy in cases with anti-phospholipid antibody syndrome like the present case.

Adult

[Increase of serum acidic isoferritins in patients with hemophagocytic histiocytosis].

We investigated serum isoferritin patterns in 2 patients with reactive hemophagocytic histiocytosis (HH) and 1 patient with neoplastic HH (malignant histiocytosis) whose serum ferritin levels were extraordinarily high. Serum ferritins in 2 patients with reactive HH were composed of mildly (pI 5.55 to 5.10) to intermediately (pI 4.81 to 4.82) acidic isoferritins, while those in patient with neoplastic HH were composed of more acidic (pI 4.70 to 4.45) isoferritins. These results indicate that the main constituents of the increased serum ferritins in HH would be acidic isoferritins, and that more acidic isoferritins would be increased in neoplastic HH than reactive HH.

Adult

[Peculiar increase of plasma plasminogen activator inhibitor 1 levels in patients with hemophagocytic histiocytosis].

There was a markedly significant increase of plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor 1 (PAI-1) and PAI activity in 3 patients with hemophagocytic histiocytosis (HPH) as compared with DIC patients with multi-organ failure (MOF). Of particular interest was the peculiar increase of PAI-1 levels, that is, the average PAI-1 level was 2,673 ng/ml, while that in DIC patients with MOF was 66 ng/ml. We conclude that the striking increase of plasma PAI-1 levels may be a pathognomonic feature of HPH and may contribute to the pathogenesis of DIC and/or MOF associated with HPH.

Adolescent

[Coincidental occurrence of idiopathic thrombocytopenic purpura in a patient with familial von Willebrand disease].

A very rare case with coincidental idiopathic thrombocytopenic purpura (ITP) and familial von Willebrand disease (vWD) was reported. A 23-year-old female was admitted because of unusual bleeding tendency lasting still after the remission of thrombocytopenic state associated with ITP. Coagulation studies indicated the presence of a mild vWD, which was thought to be responsible for the bleeding tendency. The qualitative analysis of von Willebrand factor by crossed immunoelectrophoresis and SDS-1.2% agarose gel electrophoresis showed normal multimeric composition compatible with type I vWD. vWF-inhibitor was negative, and family study revealed that her mother was also affected with type I vWD. These results suggested that there was no immediate causal relation between the two disease states. The prevalence of concomitant disease states with ITP and vWD was discussed.

Adult

[Occurrence of subdural hematoma closely associated with danazol administration in a patient with refractory ITP].

We reported a 34-year-old female patient with refractory idiopathic thrombocytopenic purpura (ITP) in whom a subacute subdural hematoma occurred without any preceding trauma during danazol administration which resulted in a marked decrease of plasma fibrinogen level. It is strongly suggested that danazol should be very carefully administered in ITP patients with serious bleeding tendency.

Adult

[Adult T-cell leukemia associated with cancer].

We observed adult T-cell leukemia (ATL) associated with cancer in four of 46 patients with ATL, including gastric cancer in two, lung cancer in one, and esophageal and gingival cancer in one. The associated cancer was recognized in three of these patients prior to the diagnosis of ATL and, in one, at autopsy. One patient suffered from a skin type of ATL, two a smoldering type and one a chronic type. No information was obtained from our patients presented here as to whether HTLV-1 influenced the appearance of other cancers, or whether the treatment for cancers influenced the appearance of ATL. Further investigations are necessary to clarify the relationship between ATL and associated cancers.

Adenocarcinoma, Mucinous

HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma.

HLA haplotypes of 27 patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) and 12 patients with adult T-cell leukemia/lymphoma (ATLL) were examined by analyzing HLA types of the patients and their family members. Either A11Bw54Cw1DR4DQw3, A24Bw54Cw1DR4DQ-, A24B7Cw7DR1DQw1, or A24Bw52Cw-DR2DQw1 and the related haplotypes were found in 70% of cases with HAM. None of these "HAM-associated" haplotypes was found in patients with ATLL. HLA haplotypes made up of HLA components of A26Bw62Cw3DR5DQw3 and one particular haplotype of Aw33B44Cw-DRw6DQw1 were associated with the ATLL haplotypes. These "ATLL-associated" haplotypes were also found in the patients with HAM who had no previous history of blood transfusion. The in vitro cultures of peripheral blood lymphocytes with HTLV-I virion antigens revealed that the response with HAM peripheral blood lymphocytes was remarkably higher than that with ATLL peripheral blood lymphocytes. Based on this HTLV-I-specific immune responsiveness, we can segregate the high responders in HAM (14 of 16 cases) and the low responders in ATLL (6 of 7 cases). The existence of high and low responders was also confirmed by the normal healthy individuals, whose responses were segregated with HAM-associated and ATLL-associated haplotypes. These results suggested that two ethnic groups in southern Kyushu may get the two different diseases, HAM and ATLL, because of their different immunogenetic backgrounds. The high immune response to HTLV-I seems to be an important genetic factor in the development of HAM.

Adult

Altered HLA antigens expressed on T and B lymphocytes of adult T-cell leukemia/lymphoma patients and their relatives.

The HLA types of peripheral blood lymphocytes (PBL) of 36 adult T-cell leukemia/lymphoma (ATLL) patients were examined and compared with those of 45 healthy relatives of these patients, and with those of 10 non-ATLL families including 80 healthy members. Thirty-one percent of ATLL patients showed either a gain or a loss of HLA antigens determined by the presence of alien HLA antigens or the absence of inherent HLA antigens deduced from familial haplotype analysis. The antigen specificity of HLA gained or lost was variable and differed from case to case among ATLL patients. Although the gain of HLA was detected only in ATLL patients, the loss of HLA was found both in ATLL patients and in asymptomatic healthy relatives. The rate of HLA loss in ATLL patients (8.4%) and their relatives (17.8%) was much higher than in relatives of non-ATLL patients (1.1%). The HLA gain and loss revealed in the PBL of ATLL patients were confirmed by altered HLA phenotypes in the cloned T and B cells established from ATLL patients. Our results suggest that latently infecting HTLV-I may induce altered HLA phenotypes in T and B cells, primarily with loss of HLA antigens in a population of asymptomatic virus carriers, and secondarily with a gain of HLA antigens after the development of ATLL.

Adolescent

Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells.

Six adult patients had a chronic progressive myelopathy that possessed the following features: high antibody titers to human T-lymphotropic virus type I (HTLV-I) in serum and cerebrospinal fluid (CSF); predominantly upper motor neuron disorder, symmetrical, with mild sensory and bladder disturbances; and presence of adult T-cell leukemia-like cells in both peripheral blood and CSF. We refer to this entity as HTLV-I-associated myelopathy (HAM). Electrophoretic studies of immunoglobulin G in CSF using Western blot analysis characteristically demonstrated p24 and p32 bands. Rates of intra-blood-brain barrier synthesis were determined and found increased in the patients with HAM. Corticosteroid treatment produced clinical improvement in all of 4 patients. A retrospective survey of CSF samples was carried out in 287 patients with neurological disorders, and 6 additional patients with HAM were identified.

Adrenal Cortex Hormones

[HTLV-I-associated myelopathy].

Following our proposal of a new clinical entity, HTLV-I-associated myelopathy (HAM), at least 270 cases have now been diagnosed in Japan. The geographical distribution resembles that of adult T-cell leukemia-lymphoma. Our laboratory has now identified 85 cases (27 males and 58 females aged 18-75 [mean 52] yrs. with age at onset 6-75 [mean 37] yrs.). The illness duration ranged from 4 mos. to 55 yrs. (mean 15.6 yrs.). Of the 85 cases, 81 lived in Kagoshima, where about 16% of the population have HTLV-I antibodies. Previously, we recognized a subgroup of cases who had frequent histories of blood transfusion, and from our recent data, 18 (21%) had the same history. The group with no history of transfusion was younger at onset of HAM (33 [SD 18] yrs. vs 49 [12] yrs.; p less than 0.05). From the latter, we have also recognized another subgroup consisting of 6 young cases (under 15 yrs.) whose mothers were positive for HTLV-I antibody titer. This group has been labeled mother-to-child or vertical transmission. Notably, the progression of symptoms was slower in the vertically transmitted group when compared to the group with a history of transfusion. We also reported the effectiveness of corticosteroids in 4 HAM cases and from the present data, 65 cases have been followed up for treatment response. Based on a 14-grade disability scoring, excellent response was noted in 20%, good in 37%, fair in 34% and no response in 9% of the total 65 cases. Compared with the vertically transmitted group, the group a history of blood transfusion appeared to have a better response to corticosteroids.

Adolescent