Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL)

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.     

Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders]

Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.     

Immune responses and serum levels of cytokines in adult T-cell leukemia patients and human T-cell leukemia virus type-I carriers.

To find predictive parameters for development and progression of adult T-cell leukemia (ATL) in human T-cell leukemia virus type-I (HTLV-I) carriers, we investigated cellular immune responses such as mitogenic responses and natural killer activity of the peripheral blood mononuclear cells (PBMC). And serum or plasma levels of cytokines, including tumor-necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and immunosuppressive acidic protein (IAP), were also measured in patients with ATL, healthy HTLV-I carriers and healthy HTLV-I non-carriers as controls. Results are as follows: (1) increased spontaneous proliferation and decreased mitogenic responses of PBMC already existed in HTLV-I carriers; (2) IAP was significantly higher in patients with acute/lymphoma type ATL than in those with chronic/smoldering type, HTLV-I carriers and HTLV-I non-carriers. These results suggest that spontaneous proliferation or mitogenic responses and IAP may be useful parameters for the development and progression of ATL from the carriers. Since HTLV-I carriers already have various grades of immunosuppression, we should seriously try to prevent further HTLV-I transmission.     

A comparative study of immunosuppressive acidic protein (IAP), CA 125 and acute-phase proteins as parameters for ovarian cancer monitoring

The serum concentrations of immunosuppressive acidic protein (IAP), CA 125, alpha-1-antitrypsin (AL-1-AT), C-reactive protein (CRP) and ceruloplasmin (COP) were determined in 63 patients with ovarian carcinoma (mean age 56.9 +/- 11.1 years). The threshold value of IAP was 640 micrograms/ml (means + 2SD), of CA 125 35 U/ml, of AL-1-AT 4 mg/ml, of CRP 12 micrograms/ml, and of COP 600 ng/ml. Eighty-three analyses of the patients with ovarian cancer coincided with tumor progression and 124 samples with remission. In women with progressive ovarian carcinoma the median IAP serum concentrations (799.3 +/- 292 micrograms/ml) were significantly increased as compared to the values of the healthy control group (48 volunteers, mean age 37.8 +/- 13.8 years; IAP 452.0 +/- 146.0 micrograms/ml). The median serum concentrations of IAP (799.3 +/- 292.2 micrograms/ml), CA 125 (933.8 +/- 1442.1 U/ml). AL-1-AT (3.8 +/- 8.7 mg/ml), CRP (31 +/- 39 micrograms/ml) were significantly elevated with progression as compared to remission (IAP 511.8 +/- 111.9 micrograms/ml, CA 125 18.4 +/- 14.4 U/ml, AL-1-AT 2.8 +/- 4.1 mg/ml, CRP 13 +/- 11 micrograms/ml). This was not the case with COP (509 +/- 761 vs. 466 +/- 106 ng/ml). A correlation between increased serum values and confirmed tumor progression was encountered in 65.1% of the patients for IAP, in 80.7% for CA 125 and in 34.9% for CRP and AL-1-AT. 98.8% false negative serum values were found for COP. Seven out of 16 and 4 out of 16 CA 125 negative samples showed right positive IAP and right positive CRP and AL-1-AT values, respectively. 88.7% of the IAP values, 92.7% of the CA 125 values, 71% of the AL-1-AT values, 93.5% of the CRP and 100% of the COP values were right negative. Our results indicate that the simultaneous determination of CA 125 and IAP enhance the efficiency of tumor monitoring in patients with ovarian cancer.     

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

The serum levels of dehydroeplandrosterone (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. © 1996 Wiley-Liss, Inc.     

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 wtih 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 β7 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 β7 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 that 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.     

Elevation of the Plasma Levels of TNF Receptor 2 in Association with Those of CD25, OX40, and IL-10 and HTLV-1 Proviral Load in Acute Adult T-Cell Leukemia

Adult T-cell leukemia/lymphoma (ATL) cells express TNF receptor type-2 (TNFR2) on their surface and shed its soluble form (sTNFR2). We previously reported that sTNFR2 levels were highly elevated in the plasma of patients with acute ATL. To investigate whether its quantitation would be helpful for the diagnosis or prediction of the onset of acute ATL, we examined the plasma levels of sTNFR2 in a large number of specimens obtained from a cohort of ATL patients and asymptomatic human T-cell leukemia virus type 1 (HTLV-1) carriers (ACs) and compared them to those of other candidate ATL biomarkers (sCD25, sOX40, and IL-10) by enzyme-linked immunosorbent assays (ELISA) and HTLV-1 proviral loads. We observed that sTNFR2 levels were significantly elevated in acute ATL patients compared to ACs and patients with other types of ATL (chronic, smoldering, and lymphoma). Importantly, sTNFR2 levels were significantly correlated with those of sCD25, sOX40, and IL-10, as well as proviral loads. Thus, the present study confirmed that an increase in plasma sTNFR2 levels is a biomarker for the diagnosis of acute ATL. Examination of plasma sTNFR2 alone or in combination with other ATL biomarkers may be helpful for the diagnosis of acute ATL.     

Serum transferrin receptor measurements in hematologic malignancies

An enzyme-linked immunosorbent assay using specific monoclonal antibodies was used to measure circulating transferrin receptor (TR) in 87 patients with various hematologic malignancies. The mean serum TR was significantly elevated in patients with myeloproliferative disorders (15.47 +/- 12.54 micrograms/ml), whereas there were no differences in chronic granulocytic leukemia (7.89 +/- 3.56 micrograms/ml), myelodysplastic disorders (9.25 +/- 4.73 micrograms/ml), and acute nonlymphocytic leukemia (3.85 +/- 3.50 micrograms/ml) as compared to normal (5.63 +/- 1.42 micrograms/ml). Among patients with lymphoproliferative disorders, the mean level was normal in lymphoma (5.73 +/- 2.59 micrograms/ml), multiple myeloma (5.47 +/- 1.31 micrograms/ml), and hairy cell leukemia (7.04 +/- 3.69 micrograms/ml). The serum TR was significantly elevated in chronic lymphocytic leukemia (CLL; 14.17 +/- 12.29 micrograms/ml), and the serum levels reflected the clinical stage of the disease. These findings suggest that serum TR measurement may provide a useful laboratory index of disease activity in certain disorders such as CLL, whereas it most likely reflects the intensity of erythropoiesis in the remaining hematological disorders that were evaluated in this study.     

Diagnosis and management of adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell leukemia virus type I (HTLV-1). Between 3% and 5% of HTLV-1-infected individuals develop ATL after a long latency. Confirmation of seropositivity of anti-HTLV-1 antibody, and clonal proliferation of CD4 and CD25 positive lymphocytes with nuclear pleomorphism in patients suspicious of malignant lymphoma or chronic lymphocytic leukemia is crucial for the diagnosis of ATL. The clinical course of ATL is very heterogeneous, and divided into acute, lymphoma, chronic, and smoldering types. The chronic type is further subclassified into the favorable and unfavorable subtypes. Acute, lymphoma, and unfavorable chronic type ATL, and favorable chronic and smoldering type ATL are defined as aggressive and indolent ATL, respectively. Recently identified prognostic indices based on clinical parameters and/or genetic predictors of outcomes need to be confirmed and incorporated for more stratified therapeutic interventions. The standard of care for aggressive ATL is multiagent chemotherapy followed by allogeneic hematopoietic stem cell transplantation if possible, while that for indolent ATL is watchful waiting until progression to aggressive ATL. The combination of interferon-α and zidovudine is also standard for leukemic type ATL. In addition, mogamulizumab, lenalidomide, and brentuximab vedotin have been incorporated into clinical practices in Japan. Furthermore, several novel drugs are currently undergoing clinical trials.     

Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma

Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.     

How I treat adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of mature activated T cells caused by human T-cell lymphotropic virus type I. ATL carries a bad prognosis because of intrinsic chemoresistance and severe immunosuppression. In acute ATL, Japanese trials demonstrated that although combinations of chemotherapy improved response rate, they failed to achieve a significant impact on survival. Patients with chronic and smoldering ATL have a better prognosis, but long-term survival is poor when these patients are managed with a watchful-waiting policy or with chemotherapy. Recently, a worldwide meta-analysis revealed that the combination of zidovudine and IFN-α is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. ATL lymphoma patients still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine/IFN. To prevent relapse, clinical trials assessing consolidative targeted therapies such as arsenic/IFN combination or novel monoclonal antibodies are needed. Finally, allogeneic BM transplantation should be considered in suitable patients.     

Urinary and serum zinc levels in chronic pancreatitis

Urinary and serum zinc levels were determined in 51 patients with chronic pancreatitis. Urinary zinc excretion in patients with chronic calcified pancreatitis (832 +/- 111 micrograms/day) (mean +/- SE) but not in noncalcified pancreatitis (684 +/- 65 micrograms/day) was significantly higher than in normal controls (418 +/- 46 micrograms/day). The urinary zinc excretion increased with deterioration of exocrine pancreatic function. Serum zinc levels in advanced pancreatitis (105.9 +/- 4.5 micrograms/100 ml) were significantly higher when compared to the pancreatitis with normal exocrine pancreatic function (91.6 +/- 3.0 micrograms/100 ml), but the difference was less pronounced than for urinary zinc excretion. This may be due to complicating diabetes, which usually lowers serum zinc. Serum zinc and urinary zinc excretion were low in a patient with chronic calcified pancreatitis complicated with a pulmonary abscess and hypoalbuminemia. In conclusion, urinary and serum zinc levels in chronic pancreatitis were increased as a result of exocrine pancreatic dysfunction. Association of diabetes may lower serum zinc, and associated malnutrition depresses both urinary and serum zinc levels.     

Measurement of serum bile alcohol levels in liver dysfunction, using isotope dilution-mass spectrometry

We determined the concentration of two major serum bile alcohols, 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol, in healthy controls and patients with acute hepatitis, chronic hepatitis, and cirrhosis, using isotope dilution-mass spectrometry. In healthy controls the mean total amount of the two major bile alcohols was 9.6 +/- 3.4 ng/ml (mean +/- SD). In patients with liver diseases the mean values were as follows: acute hepatitis, 44.8 +/- 18.2 ng/ml; chronic hepatitis, 18.2 +/- 5.6 ng/ml; Child grade A cirrhosis, 37.9 +/- 26.0 ng/ml; Child grade B, 42.7 +/- 22.0 ng/ml; and Child grade C, 71.2 +/- 24.2 ng/ml. The mean ratio of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol to 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol in patients with Child grade C cirrhosis was significantly higher than that in healthy controls (1.42 +/- 0.92 versus 0.61 +/- 0.11; p less than 0.05).     

OX40 Signaling Renders Adult T-Cell Leukemia Cells Resistant to Fas-Induced Apoptosis

We reported previously that OX40, a member of the tumor necrosis factor receptor family, is expressed constitutively on fresh leukemia/lymphoma cells isolated from patients with adult T-cell leukemia (ATL). In this study, we tested whether OX40 signaling affects the Fas-mediated apoptosis of fresh ATL cells isolated from 7 patients (3 acute type, 3 chronic type, and 1 smoldering type). In all these patients, the coculture of ATL cells with MMCE/OX40 ligand gp34, a stable human gp34 transfectant of a mouse epithelial cell line, resulted in a decrease in the percentage of apoptotic cells after treatment with anti-Fas monoclonal antibody, compared to coculture with MMCE/mock controls. Similar findings were obtained in OX40(+)- human T-cell leukemia virus type I-transformed T-cell lines. To elucidate the molecular mechanism of this phenomenon, we used Kit225/OX40, a stable OX40 transfectant of an IL-2-dependent T-cell line, and its deletion mutant, Kit225/del-OX40, in which the intracytoplasmic domain of OX40 had been deleted. Coculture with MMCE/gp34 inhibited the apoptosis of Kit225/OX40, but Kit225/del-OX40 apoptosis was hardly affected. These results suggest that ATL cells may escape Fas-mediated destruction of the immune system through OX40 signaling.     

Lactoferrin secretion in alcoholic pancreatic disease

Lactoferrin, a nonenzyme protein normally secreted in small amounts in pancreatic juice, has been reported by several investigators to be secreted in large amounts in chronic pancreatitis. Whether this increased secretion first occurs at an early or late stage of alcoholic pancreatic disease is unknown. In this study we measured lactoferrin and enzyme outputs in duodenal juice from 10 healthy subjects and three groups of alcoholic subjects: asymptomatic chronic alcoholics without evidence, clinically or biochemically, of pancreatitis (10), those recovered from acute pancreatitis (8), and those with established chronic pancreatitis (8). A multilumen, marker-perfused duodenal catheter was used to aspirate basal pancreatic secretions at the ligament of Treitz. The mean ( +/-SE) lactoferrin concentration in duodenal juice for the four groups of subjects was: healthy, 0.7 +/- 0.1 micrograms/ml; asymptomatic alcoholics, 5.5 +/- 1.5 micrograms/ml; alcoholics who had recovered from acute pancreatitis, 7.4 +/- 0.8 micrograms/ml; and alcoholics with chronic pancreatitis 7.1 +/- 1.9 micrograms/ml. The three groups of alcoholics each had a greater lactoferrin concentration than the normals (P less than 0.005). The output of lactoferrin in the four groups paralleled the concentration in that the three groups of alcoholics had a significantly greater output: healthy subjects, 3.4 +/- 0.5 micrograms/kg/hr; asymptomatic alcoholics, 25.7 +/- 7.4 micrograms/kg/hr; alcoholics recovered from acute pancreatitis, 80.1 +/- 27 micrograms/kg/hr; and alcoholics with chronic pancreatitis, 90.9 +/- 32 micrograms/kg/hr. The output of chymotrypsin and trypsin in the four groups of subjects revealed increased secretory rates in the asymptomatic alcoholics and the alcoholics recovered from acute pancreatitis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adult T-cell leukemia-lymphoma: current treatment strategies and novel immunological approaches

Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy, closely associated with human T-cell lymphotropic virus type I infection. Clinically, ATL is classified into four subtypes: acute, lymphoma, chronic and smoldering type. Although the prognosis of chronic and smoldering-type ATL is relatively good, that of patients with acute- or lymphoma-type ATL still remains extremely poor. Zidovudine/IFN-α therapy seems to be promising, although its efficacy has not yet been confirmed in well-designed prospective studies. High-dose chemotherapy with the support of autologous transplantation does not improve outcome. Allogeneic stem cell transplantation is promising and approximately 40% of aggressive ATL patients are expected to survive long-term, although transplantation-related mortality is as high as 40-50%. Stem cell transplantation using reduced-intensity conditioning is also effective and safer, with graft-versus-ATL and graft-versus-human T-cell lymphotropic virus type I effects observed after transplantation. Novel approaches including new agents such as purine nucleoside phosphorylase inhibitors and histone deacetylase inhibitors, or targeted immunotherapy using antichemokine receptor-4 antibody or dendritic cell/peptide vaccine are also warranted.     

Chromosomal aberrations in adult T cell leukemia: relationship to the clinical severity

A chromosome study was performed in 18 patients with adult T cell leukemia (ATL), who were divided into three groups according to their clinical manifestations: nine had acute ATL, six had chronic ATL, and three had smoldering ATL. Mitotic cells were obtained from peripheral blood, lymph node, or bone marrow and were analyzed by the G-banding technique. In acute ATL, the chromosome number ranged from diploid or pseudodiploid to hyperdiploid; in the chronic type, from hypodiploid to hyperdiploid; but in the smoldering type, it was diploid. Eight of nine patients with acute ATL had trisomy 3 and/or trisomy 7, whereas none of those with chronic ATL exhibited these aberrations. Patients with smoldering ATL had a normal karyotype. The present findings indicate that the more aggressive the clinical course of ATL, the more complex the numerical and structural chromosome abnormality.     

Soluble adhesion molecules and anti-endothelial cell antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy

OBJECTIVE: To examine whether levels of soluble adhesion molecules and anti-endothelial cell antibodies (AECA) were elevated in rheumatoid arthritis (RA) complicated by peripheral neuropathy compared to controls with no neurological complications. METHODS: Levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, and AECA were determined by ELISA in 33 patients with RA neuropathy, 23 patients with vasculitis who had no neurological complications, 29 patients with RA without neuropathy, and 25 healthy volunteer controls. RESULTS: The patients with neuropathy had significantly higher levels of serum sVCAM-1 (mean 1119+/-368 ng/ml) than patients without neuropathy (mean 869+/-214 ng/ml) and healthy controls (mean 578+/-204 ng/ml). Serum levels of sE-selectin were higher among neuropathic patients with RA (mean 73+/-34 ng/ml) than RA controls (mean 45+/-27 ng/ml) and healthy controls(mean 32+/-10 ng/ml). There was no significant difference in serum levels of sVCAM-1, sE-selectin, and AECA between patients with RA with neuropathy and patients with vasculitis uncomplicated by neurological disease. Abnormal levels of sVCAM-1, sE-selectin, or AECA were found in sera from 28 (85%) patients with RA neuropathy, 15 (65%) patients with vasculitis, 9 (31%) RA controls, and 2(8%) healthy controls. CONCLUSION: Serum levels of sVCAM-1, sE-selectin, and AECA are higher in patients with RA neuropathy than in patients with RA uncomplicated by neurological disease. These data suggest that development of peripheral neuropathy in RA is associated with increased endothelial cell activation.     

Selenium levels and glutathione peroxidase activities in patients with acute myocardial infarction

OBJECTIVE: Selenium (Se) is part of the enzyme glutathione peroxidase (GSH-Px) that plays an important role in the antioxidant defence of the body, including the myocardium, against the deleterious actions of free radicals and lipid peroxides. In order to evaluate the Se status and the GSH-Px activity in ischaemic heart disease, plasma, erythrocyte and urinary Se concentrations together with plasma and erythrocyte GSH-Px activities were determined in 27 patients diagnosed as acute myocardial infarction (AMI). The control group consisted of 24 age-matched healthy individuals. METHODS AND RESULTS: Fasting blood and urine samples were collected within 24 hours after the onset of chest pain. Mean plasma, erythrocyte and urine Se concentrations were significantly lower in the patient groups (63.7 +/- 12 micrograms/l, 0.48 +/- 0.04 microgram/g Hb and 49.6 +/- 27.7 micrograms/g creatinine, respectively), compared to controls (82.2 +/- 14.6 micrograms/l, 0.51 +/- 0.03 microgram/g Hb and 93.4 +/- 62.6 micrograms/g creatinine, p < 0.001, p < 0.02 and p < 0.003, respectively). No statistically significant difference was found between mean plasma GSH-Px activity in patients (0.36 +/- 0.1 U/ml) and controls (0.35 +/- 0.09 U/ml), whereas erythrocyte GSH-Px activity was higher in patients (48.1 +/- 10.2 U/g Hb) than in the controls (35.3 +/- 9.1 U/g Hb, p < 0.001). CONCLUSION: Our findings confirm the previous studies and demonstrate that patients suffering from AMI exhibit lower plasma, erythrocyte and urinary Se than the controls. Since the erythrocyte Se level represents a measure of the Se status over a period of several weeks due to its long biological half-life, low Se levels observed in the patient group might have been present before the acute event, thereby suggesting an aetiologic relevance. The presence of increased erythrocyte GSH-Px activity in these patients may be interpreted as an antioxidant defence against the chronic oxidant stress present before the AMI, presumably due to the process of coronary atherosclerosis.     

Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma

The feasibility of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) in 11 patients with adult T-cell leukaemia/lymphoma (ATL) (6 acute, 4 lymphoma, 1 chronic type) was evaluated. The preparative regimens (9 conventional, 2 reduced-intensity) were tolerable. Five patients developed acute graft-versus-host disease (GVHD), and three, extensive chronic GVHD. All 10 patients who survived > 30 d achieved complete remission. Estimated 1-year overall and disease-free survival rates were 53 +/- 30% and 45 +/- 29% respectively. Four patients remain alive and disease-free at a median follow-up of 25 months. The others died of transplantation-related complications. This pilot study suggests that allo-HSCT in ATL should be evaluated further.