Tumor-directed cytotoxicity in multiple myeloma--the basis for an experimental treatment approach with interleukin 2.

There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be putative targets for immunotherapeutic approaches. Peripheral blood T lymphocytes are capable of suppressing monoclonal immunoglobulin production of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or interleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocytes as demonstrated in a cytotoxicity assay using purified MM plasma cells as targets.

Sickle cell anemia and beta-gene cluster haplotypes in Cuba.

We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.

Functional and biochemical characteristics of a soluble B lymphocyte proliferation-inhibiting activity produced by bone marrow cells from multiple myeloma patients.

Several mechanisms are discussed as inducers for polyclonal hypogammaglobulinemia in multiple myeloma. A soluble noncytotoxic activity which inhibits in vitro the proliferation of normal polyclonal spleen B lymphocytes was measured in the supernatant of cultured bone marrow mononuclear cells from multiple myeloma patients. In addition, human B lymphoblastic cell lines (CESS, Daudi) and human T lymphocytes were sensitive to the antiproliferative effect of the suppressor activity, while other cell lines (RPMI 8226, IM9, CTL6, L1210, HL-60, and K562) were not.

Clomipramine treatment of paraphilias in elderly demented patients.

Sexually inappropriate conduct often accompanies the disinhibition associated with dementia and neuropsychologic deficits. Management of these behaviors is problematic and time consuming. We report two cases in which paraphilias responded to treatment with clomipramine.

Low-dose recombinant interleukin-2 therapy in advanced multiple myeloma.

In vitro data have demonstrated autologous T-lymphocytes with anti-tumour activity in multiple myeloma (MM). Therefore a phase I/II trial was conducted to study the feasibility, the effect on several immunological parameters, and the tumour response induction of low-dose recombinant interleukin-2 (rIL-2) in MM patients. 18 MM patients of advanced stages in progress, who had failed on standard chemotherapy received 9 x 10(6) IU/m2 rIL-2 twice daily on days 1 and 2 and 0.

A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group.

406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.

Analysis of beta-thalassemia mutations in the United Arab Emirates provides evidence for recurrent origin of the IVSI nt 5 (G-C) mutation.

Beta-thalassemia mutations were characterized in a sample of 70 patients from United Arab Emirates (U.A.E.

An accurate 3-D model for magnetic stimulation of the brain cortex.

We present a 3-D model for the simulation of a realistic clinical situation during magnetic stimulation. The electromagnetic problem is solved by reconstructing the inhomogeneous head tissues from magnetic resonance images and associating relative values of conductivity to each tissue. Application of Maxwell's equations in the integral form leads to an equivalent 3-D electrical network, whose solution gives the current density distribution in the brain.

Characterization of cloned class I MHC-restricted, CD8+ anti-Meth A cytotoxic T-lymphocytes: recognition of an epitope derived from the Meth A gp110 tumor rejection antigen.

Meth A gp110 has been tentatively identified as a tumor rejection antigen. Following isolation of a class I major histocompatibility complex (MHC)-restricted, CD8+ anti-Meth A cytotoxic T-lymphocyte (CTL), we sought to determine whether the determinant recognized by this CTL was: (a) functional in tumor rejection of Meth A sarcoma; and (b) derived from Meth A gp110. Initially, we isolated an anti-Meth A CTL-resistant variant of Meth A sarcoma, Meth A4R, by immunoselection.

Bleeding time in patients with cirrhosis: relation with degree of liver failure and clotting abnormalities. C.A.L.C. Group. Coagulation Abnormalities in Cirrhosis Study Group.

Patients with cirrhosis suffer from a complex haemostatic disturbance, due to abnormalities in clotting and fibrinolytic system activation and in primary haemostasis. The latter is indicated by a prolongation of bleeding time, which is a reliable indicator of platelet function in vivo. To further assess the relationship between bleeding time, degree of liver failure and clotting abnormalities in patients with cirrhosis, bleeding time was investigated in a prospective study of 70 consecutive patients with cirrhosis diagnosed by liver-needle biopsy, of whom 19 belonged to Child-Pugh class A, 29 to B and 22 to C.

A report on 528 intragenic deletions detected in DMD and BMD patients by an Italian collaborative study.

The results of a collaborative study involving about one third of the total DMD and BMD cases living in the Italian territory are reported. The analysis of the breakpoint frequency by intron revealed significant differences among regional groups of DMD patients (for introns 2, 11 and 50 in Sardinia and for introns 9 and 45 in northeastern Italy), whereas no regional differences were observed among regional groups of BMD patients. These differences involve the same Italian regions which previous studies, performed by different markers, identified as "genetically differentiated".

Association between prolonged bleeding time and gastrointestinal hemorrhage in 102 patients with liver cirrhosis: results of a retrospective study.

Background: Gastrointestinal bleeding is a frequent complication of liver cirrhosis (LC) and represents an important warning sign of imminent death. Platelet dysfunction is an abnormality occurring prevalently in severe liver failure, and could well predispose to bleeding.

Methods: One hundred and two patients with liver cirrhosis diagnosed by needle liver biopsy were studied.

Prognostic value of clinical, laboratory, and histological characteristics in multiple myeloma: improved definition of risk groups.

Follow-up data of 320 multiple myeloma (MM) patients entering the German Myeloma Treatment Group (GMTG) trial MM01 were analysed for factors predicting overall (OAS) and tumour related survival (TRS). Response to primary induction chemotherapy was relevant for prognosis if a limit of 25% tumour cell mass (TCM) reduction was used to separate responders from non-responders. Furthermore, TCM, histological grading of myeloma cells, degree of bone marrow infiltration, haemoglobin, platelet counts, calcium, creatinine, albumin, beta 2M, and Bence Jones proteinuria correlated to both OAS and TRS.

Computer modelling of brain cortex excitation by magnetic field pulses.

In spite of many clinical and experimental applications, the technique of transcranial magnetic stimulation still presents obscure aspects. This especially concerns safety parameters and the exact characterization of the current induced by a single magnetic pulse. The model proposed consists of an equivalent electric network derived by Maxwell's equations and applied to discretized magnetic resonance imaging of a normal subject.

Differences in activation of normal and glycosylphosphatidylinositol-negative lymphocytes derived from patients with paroxysmal nocturnal hemoglobinuria.

In these studies, the role of glycosylphosphatidylinositol (GPI)-anchored surface molecules during T cell activation was investigated in fresh T cells and T cell lines obtained from patients with paroxysmal nocturnal hemoglobinuria. For control, GPI-expressing T cells of the same patients were used. Unstimulated GPI- T cells exhibited significantly reduced surface expression of the activation Ag CD45R0, compared with GPI+ T cells.

CD16- CD56+ natural killer cells after bone marrow transplantation.

Natural killer (NK) cells are phenotypically defined as lymphocytes expressing the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3- CD16- CD56+ NK cell subset has been described in normal individuals representing less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for their reconstitution of the immune system during follow-up after autologous or allogeneic bone marrow transplantation.

Analysis of CD16+dim and CD16+bright lymphocytes--comparison of peripheral and clonal non-MHC-restricted T cells and NK cells.

The Fc gamma RIII receptor (CD16) has been described on natural killer cells and a small subset of T lymphocytes. CD16+bright lymphocytes represent the typical population of peripheral blood CD3- NK cells. In these studies in addition to CD16+bright NK cells Fc gamma RIII expressing cytotoxic T lymphocytes in peripheral blood from one healthy individual are characterized as CD16+dim non-MHC-restricted CTLs either expressing the alpha/beta (80%) or the gamma/delta T cell receptor (20%).

Multiparameter analyses of normal and malignant human plasma cells: CD38++, CD56+, CD54+, cIg+ is the common phenotype of myeloma cells.

Plasma cells obtained from bone marrow samples of 45 patients with MM, eight patients with MGUS, eight patients with Waldenström's macroglobulinaemia (WM), one patient with immunocytoma, and 12 controls were characterized by immunophenotyping, estimation of DNA content, and labeling index, as well as by morphological analysis. Plasma cells from 37/45 myeloma and 5/8 MGUS patients expressed CD38 and CD56 (N-CAM) on their surface but were negative for other NK cell-associated antigens such as CD16 (Fc gamma RIII) or CD2. All tumor cells of less-differentiated cell type (WM, immunocytoma) and normal polyclonal plasma cells were negative for CD56.