摘要:

Since 1976, we have performed more than 240 fetal tissue transplants (FLTs) to treat 63 patients with severe immunodeficiency disease (IDD), with inborn errors of metabolism (IEM), or with severe aplastic anemia. In both IDD and IEM, FLT into postnatal recipients has demonstrated beneficial effects (67% of the patients were either cured or improved significantly). In 1988, we developed in utero FLT into human fetuses, taking advantage of the immunological tolerance of young fetuses. The transplants have involved fetuses suffering from various diseases at 12-28 weeks postfertilization with 2 of the 6 cases eventually resulting in abortion. With the 4 other fetuses, a favorable outcome was observed: 3 children are now more than 4 years old, and are alive and well with evidence of engraftment, reconstitution of immunity, and partial correction of β° thalassemia. In the fourth case, the fetus is alive and well and birth is expected soon. In utero transplantation of stem cells is a therapy with remarkable advantages: (a) tolerance induction due to the immune immaturity of the host, (b) lack of graft-versus-host disease due to the immaturity of the donor, (c) ideal isolation of the fetus in the maternal uterus, and (d) an optimal environment for donor fetal cell development in the vicinity of host fetal cells and growth factor

ISSN:0001-5792    

DOI:10.1159/000203741

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The differences between reactive and malignant processes are sometimes blurred. Homogeneity is no longer a requisite for the diagnosis of lymphoma, as witnessed in mucosa-associated lymphatic tissue lymphoma and T-cell-rich B cell lymphoma, which are composed of an admixture of neoplastic clonal B cells and reactive T cells which occasionally are very prominent in the histological picture. Infectious mononucleosis, anaplastic large cell lymphoma, composite lymphoma and Hodgkin’s disease, all share many similarities and may actually represent a continuous spectrum of pathological conditions. Immunodeficiency states, whether primary or acquired, are commonly associated with clonal lymphatic malignancies preceded by a polyclonal lymphoproliferative stage, which is usually reversible by reducing immunosuppression. The distinction between these stages is sometimes difficult to assess. Immunologists have so far failed to find a lymphatic tumor-specific antigen, hence, monoclonality is usually based on a constellation of factors, namely homogeneity of the phenotypic expression of few antigens, aberrant expression of antigens and restricted expression of κ- or λ-chains in malignancies expressing surface immunoglobulins. Nonrandom chromosomal translocations as well as other aberrations, usually important in the diagnosis of malignancy, are sometimes of limited value. This is mainly due to the existence of translocations [like t(14;18) and t(2;5)] in nonmalignant states, and their non-specificity [the existence of t(8;14) in Burkitt’s lymphoma and large cell lymphoma, t(2;5) in Hodgkin’s disease and anaplastic large cell lymphoma, and t(14;18) in large cell lymphoma evolving from follicular lymphoma and Burkitt’s lymphoma]. The diagnostic tools available in 1995, although usually sufficient, are sometimes unable to distinguish between malignancy and reactivity. Some problematic cases will be more accurately defined as lying in the gray zone, or as belonging to a spectrum ranging between reactivity and m

ISSN:0001-5792    

DOI:10.1159/000203742

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Between August 1985 and January 1994, 73 evaluable adult patients with bulky localized or advanced-stage, intermediate- and high-grade de novo non-Hodgkin’s lymphoma (NHL) were treated with MECOP-B (methotrexate and leucovorin rescue, epimbicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Over a median follow-up of 32 months (range, 4-98 months), 55 patients (75%) achieved complete remission (CR) (95% confidence interval, 81-69%) and 3 attained partial remission (PR) (4%) for an overall response rate of 79%. Using a multiple regression analysis where the dependent variable was response to therapy (CR vs. PR + treatment failure), poor performance status, and the presence of a bulky disease were negatively associated with the likelihood of achieving CR. Survival analysis showed that 49 (67%) patients (95% confidence interval, 74 and 60%) were alive, of whom 47 (64%) were disease-free. While the median survival has not been reached, the actuarial survival probability at 5 years ± SE was 64 ± 6%. Time to treatment failure for those attaining CR was also estimated. While the median survival has not been reached, probability of freedom from treatment failure at 5 years ± SE was estimated as 74 ± 7%. However, the long-term CR (CR rate times disease-free survival rate) was only 48%, and the ‘measurement of efficacy’ was 53%. These results were inferior to those from our earlier reports. The proportional hazards model of Cox identified poor performance status, older age, and high lactate dehydrogenase as factors with an adverse effect on survival. Using the results of the model, patients were categorized into three predefined risk groups with significant differences in outcome. Toxicity of the regimen was high, but comparable to that reported in the literature with a toxic death rate of 8%. We conclude that MECOP-B is an effective therapy for patients with aggressive NHL; however, based on the current results as compared with our earlier analysis, besides the emergence of prognostic factors, therapy of NHL should be individualized. Less expensive, less toxic regimens should be used for lower-risk patients, while the use of more intense, more toxic, more expensive programs should only be offered to those with a predicted poo

ISSN:0001-5792    

DOI:10.1159/000203743

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We have compared three techniques for the detection of plasma circulating antiplatelet antibodies, i.e., the platelet suspension immunofluorescence test (PSIFT), the platelet radioactive antiglobulin test (PRAT), and the monoclonal antibody immobilization of platelet antigens (MAIPA). Frozen plasma samples from patients with idiopathic thrombocytopenic purpura or HIV-associated thrombocytopenia were used in the study. The PSIFT and PRAT showed the appropriate ease of performance necessary for screening purposes. The PSIFT is free of radioactivity hazards, but seemed to be less sensitive than the PRAT. The MAIPA is a useful tool to detect antibodies against glycoproteins (GPs) Ib/IX and IIb/IIIa. However, in comparison to PSIFT and PRAT, MAIPA is more time consuming, requires considerable technical expertise, and the identification of antiplatelet activity is highly dependent on the selection of an appropriate primary anti-GP monoclonal antibody. This could explain the lower prevalence of antiplatelet activity detected by MAIPA, in comparison to the frequency provided by the PSIFT and PRAT.

ISSN:0001-5792    

DOI:10.1159/000203744

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We studied 14 adult patients presenting with fever and cytopenia of the peripheral blood and histiocytic hyperplasia with hemophagocytosis (HHH) in the bone marrow regarding an association of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) by using in situ hybridization (ISH) and also evaluated the clinical and laboratory findings according to the encountered organisms. ISH using a CMV RNA probe demonstrated infected cells in 6 out of 14 cases (43%), and ISH using an EBV EBER RNA probe demonstrated infected nuclei in 5 out of the same 14 cases (36%) of HHH. No cases showed a positive reaction with both probes. Three cases showed a negative reaction with both probes. The mean age of all patients was 29 years; and that of the CMV-positive patients was 27 years and that of the EBV-positive patients was 36 years. Organomegaly was found in 3 out of 6 CMV-positive patients (1 hepatomegaly, 1 splenomegaly, 1 hepatosplenomegaly), and 4 out of 5 EBV-positive patients (lymphadenopathy in all 4 cases, hepatosplenomegaly in 2 cases). One of the CMV-positive case had acute myeloblastic leukemia, and 2 EBV-positive cases had underlying malignancy (1 Hodgkin’s disease, 1 non-Hodgkin’s lymphoma). Seven out of the 14 HHH cases (50%) died within several months after diagnosis. Nucleic acid hybridization methods can be used for the routine examination of the association of CMV or

ISSN:0001-5792    

DOI:10.1159/000203746

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Erythrocyte production was measured in 21 iron deficiency anemia patients after therapy with parenteral iron. The red cell mass was measured twice with 51Cr and red blood cell survival by labeling with 51Cr. In all cases, erythrocyte production increased in the 12 h following parenteral iron administration (dextran or polysaccharide-iron oxide). Production increased sharply for 3 to 6 days, remained high for 2 or 3 days and fell sharply thereafter. It is suggested that this fall is not due to a lack of available iron.

ISSN:0001-5792    

DOI:10.1159/000203748

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes of 92 βs GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with coexistent α-thal trait did not have severe recurrent infections and none had gallstones. The high frequencies of the Saudi Arabia/India βs haplotype and α-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti Arabs comparable to that in eastern S

ISSN:0001-5792    

DOI:10.1159/000203753

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Interleukin 6 (IL6) secretion by blast cells derived from peripheral blood of patients with acute myelogenous leukemia (AML) was characterized. IL6 secretion showed a wide variation both when AML blasts were cultured in medium alone and in the presence of exogenous cytokines. The level of IL6 secretion was significantly correlated to secretion of other cytokines (IL1α, IL1β, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α). IL1β, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and stem cell factor increased IL6 secretion, whereas IL4 caused decreased IL6 secretion together with increased release of IL1 receptor antagon

ISSN:0001-5792    

DOI:10.1159/000203754

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the α2/α1-, α/β-, and γ/β-mRNA ratios in subjects with β -thalassemia (β-thal), hereditary persistence of fetal hemoglobin (HPFH), and normal adults. The α- and β -globin gene mutations were characterized with gene mapping, PCR, and DNA sequencing. The average α2/α1-mRNA ratio was the same in normal adults and β-thal heterozygotes with four α-globin genes (2.61-2.63) or with an α-thal-2 trait (1.48-1.55). The average α/β -mRNA ratios were 4.47 and 3.84 in normal adults with four α-globin genes and with α-thal-2 trait (-α/αα), respectively. There was an increase of ∼ 50% in ιs β -thal heterozygotes with transcriptional mutants [-88 (C→T) and -29 (A→G)] with lower alues (∼ 25%) in those with α-thal-2 trait (-α/αα). High α/β ratios were also observed for heterozygotes for nonsense or frameshift mutants located in exon 1 or exon 2. Increases of -150-165% were seen in subjects with RNA processing defects; an exception was the IVS-I-110 (G→ A) mutation with a normal value in the heterozygote. The increases were also less pronounced in heterozygotes for the codon (CD) 121 (G→T) mutation and the CDs 134-137 insertion/deletion. Normal α/(γ+β) values were seen in 3 heterozygotes each with a different deletion involving part of the β -globin gene. The presence of the silent β -thal allele, -101 (C→T), in trans to a CD 8 (-AA) allele has a minor effect on the α/β-mRNA ratio. The α/β -mRNA ratio in HPFH heterozygotes was ∼ 145% of normal, but with a γ-mRNA level of 35.4-44.7% the calculated α/(γ+β) ratio became as in normal adults. The RT-PCR methodology appears useful in expression studies in β -thal (and HPFH) and values of mRNA appear to correspond t

ISSN:0001-5792    

DOI:10.1159/000203768

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Patients with primary or secondary immunodeficiency are at high risk for B cell lymphoproliferative syndromes (LPS) that are generally Epstein-Barr virus (EBV)-associated. We established a cell line, termed JuWa, from an immunoblastic lymphoma that developed in a child with severe combined immunodeficiency. JuWa cells were representative of the original lymph node as shown by a similar IgH gene rearrangement pattern. The cell line exhibited the typical features of a lymphoblastoid cell line (LCL): (1) growth pattern in large clumps, (2) lack of structural chromosome abnormalities, (3) type III latency with expression of EBV-associated EBNA2 and LMP, as well as B cell activation markers CD23 and CD30, thereby showing characteristics of an EBV producer cell line, i.e. a latent infection with a small subpopulation of cells spontaneously entering the lytic cycle, (4) inducibility of the lytic cycle by IdU and TPA, leading to an increase of early antigen and viral capsid antigen-positive cells from 1 to 15-20%, and (5) elimination of the linear viral genomes by treatment with acyclovir (ACV), without affecting the circular episomal genomes. After withdrawal of ACV, viral replication resumed within 7 days. Thus, JuWa cells support the concept of the LCL-like features of LPS and lymphomas occurring in the setting of immunodeficiency. In our in vitro model, ACV treatment could effectively suppress the viral replication but not cure EBV infection of B cells.

ISSN:0001-5792    

DOI:10.1159/000203769

出版商:S. Karger AG    

年代:1996

数据来源: Karger