Molecular genetic and immunohistochemical analyses of a case of multicentric Castleman's disease

Whether Castleman's disease is primarily hyperplastic or neoplastic in nature is a matter of controversy; however, the classical localized form has been thought clinically benign in itself, because it can be cured by local therapy. Recently, a multicentric form of the disease has been reported and has received attention because of its aggressive clinical course and high incidence of developing malignant lymphoma. Here, we describe a case of multicentric Castleman's disease which occurred in a 24-year-old Japanese man. To ascertain whether a monoclonal population was present or not, we performed a molecular genetic analysis of the genes encoding the T-cell receptor and the immunoglobulin, as well as a conventional immunohistochemical analysis. Using these sensitive methods, no monoclonal population could be found. The findings suggest that our case represents a reactive rather than a neoplastic disorder.     

Concurrent Adult T-Cell Leukemia and Acute Myeloblastic Leukemia

A 49-year-old man developed adult T-cell leukemia (ATL) andacute myeloblastic leukemia (AML) at the same time. Using Southernblotting analysis, the leukemic cells of the ATL were foundto contain the human T-cdl leukemia virus type I (HTLV-I) proviralgenome, whereas those of the AML did not, indicating the HTLV-Inot to be associated with the AML oncogenesis. At the initialpresentation, the serum anti-HTLV-I antibody was judged on screeningby a routine particle-agglutination (PA) test and an indirectimmunofluorescence assay (IF) to be negative. By Western blottinganalysis, however, the serum was proved to be positive for anti-HTLV-Iantibody. These results indicate that a routine PA-test andan IF way show false negative reactions on very rare occasionsof low antibody titer. This is the first report of a coincidenceof ATL with another type of leukemia.     

Double-door laminoplasty using autologous spinous process for the management of cervical myelopathy

We describe a technique of double-door laminoplasty for the management of cervical myelopathy using the autologous spinous process instead of an artificial spacer. The aims in the present study were to determine the fusion rate and the incidence rate of breakage in the autologous spinous process, and to assess its efficacy for cervical laminoplasty. Twenty-three patients of cervical myelopathy were treated with double-door laminoplasty followed by implantation of the autologous spinous process. The spinous process from C3 to C7 was resected, at 8 mm from the basal part of the spinous process. The autologous spinous process was made from the removed spinous process, and was implanted between each expanded laminae. Post-operative CT scanning determined the fusion rate between the expanded laminae and the autologous spinous process as 70.4% at 3 months, and 93.5% at 6 months, after the operation. There was no dissociation and no breakage in the autologous spinous process during the follow-up observation period. There were certain advantages to our technique including the high fusion rate and good stability in the autologous spinous process. In addition, this technique was less expensive than other techniques using an artificial spacer. These findings indicated that this technique was a reliable procedure for effectively treating of cervical myelopathy which are caused by multisegmental cervical canal stenosis.     

Antitumor activity of human interferons: their direct cytotoxic activity and clinical effects

It was found that both interferon-beta and interferon-alpha had a direct cytotoxic action against a few sensitive cultured cell lines. The action was not concentration dependent, but time dependent. Interferons expressed their maximum effect when they were given daily for long time to nude mice bearing transplantable ascitic human cancer cell lines, indicating that interferons had schedule dependency. In preliminary phase II study of interferons (3-9 X 10(6) U daily im, iv or local use) to 40 patients with various malignancies, only one patient with B-cell lymphoma responded to systemic use of both interferons and two out of five patients with pleural malignant effusion of breast cancer also responded to intrapleural use of interferons. Side effects were usually mild, but included fever, weakness, gastrointestinal, hematopoietic, liver and kidney function disturbances.     

Factors affecting ST depression during cardiopulmonary exercise testing in patients with mitral stenosis without significant coronary lesions

Symptom-limited cardiopulmonary exercise testing was performed in 37 patients with mitral stenosis (MS) without significant coronary artery stenosis to evaluate factors affecting ST depression in exercise electrocardiograms. The degree of ST depression was not associated with gender or exercise tolerance. The incidence of significant ST depression was higher in the patients receiving than in those not receiving digitalis (P < 0.05). In addition, the patients with atrial fibrillation and a higher heart rate response were more likely to have a high prevalence of significant ST depression than those with sinus rhythm and a lower response (P < 0.05). We concluded that atrial fibrillation, a higher maximum heart rate, and oral digitalis administration were involved in ST depression during exercise testing in patients with mitral stenosis without coronary heart disease.     

Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project

Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)-cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.     

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.     

Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis

The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus for treating rheumatoid arthritis (RA) patients in clinical practice. Fifty-five active RA patients who had been resistant or intolerant to other disease-modifying antirheumatic drugs were enrolled in this open-label trial. Patients were administered tacrolimus at a dosage of 1, 2 or 3 mg once daily, and followed up for 24 weeks. They were divided into three groups according to their dosage. Efficacy and safety were evaluated utilizing clinical and laboratory findings. Eighty percent of the patients had moderate or high disease activity; 55% were elderly and 53% had complications; 65% of the patients were started on tacrolimus as a monotherapy. Moderate or good response rates were achieved as follows: 38.2% (4 weeks); 41.8% (12 weeks); and 45.6% (24 weeks). Adverse events were observed in seven cases (12.7%). Only one case required hospitalization due to severe hyperglycemia caused by a high tacrolimus concentration (24.2 ng/ml); we suspected a drug interaction in this subject. Mean concentrations were dose-dependent in the 1, 2, and 3 mg/day groups (2.96, 4.29, and 8.32 ng/ml, respectively). Four cases of high concentration (over 10 ng/ml), without any signs or symptoms, were observed in the 3 mg/day group; in these cases, doses were decreased and no severe adverse events occurred. Tacrolimus was found to be both effective and safe in treating active RA patients with complicated backgrounds in clinical practice. Blood concentration measurements and dose adjustments should be performed to prevent severe adverse events in a 3 mg/day group. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

TCRzeta mRNA splice variant forms observed in the peripheral blood T cells from systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology. Tyrosine phosphorylation and protein expression of the T-cell receptor ζ chain (ζ) have been reported to be significantly decreased in SLE T cells. In addition, ζ mRNA with alternatively spliced 3′ untranslated region (ζmRNA/as-3′UTR) is detected predominantly in SLE T cells, and aberrant ζ mRNA accompanied by the mutations in the open reading frame including ζ mRNA lacking exon7 (ζmRNA/exon7-) is observed in SLE T cells. These ζ mRNA splice variant forms exhibit a reduction in the expression of TCR/CD3 complex and ζ protein on their cell surface due to the instability of ζ mRNA splice variant forms as well as the reduction in interleukin (IL)-2 production after stimulating with anti-CD3 antibody. Data from cDNA microarray showed that 36 genes encoding cytokines and chemokines, including IL-2, IL-15, IL-18, and TGF-β2, were down-regulated in the MA5.8 cells transfected with the ζ mRNA splice variant forms. Another 16 genes were up-regulated and included genes associated with membranous proteins and cell damage granules, including the genes encoding poliovirus-receptor-related 2, syndecan-1, and granzyme A.