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Biomedical subjects

A Toren

Publications and source records attributed to A Toren.

At least 37 records · Page 2Linked to original sources
PubMed1999

Successful human umbilical cord blood stem cell transplantation without conditioning in severe combined immune deficiency.

A 2-month-old girl with severe combined immunodeficiency (SCID), presented with mild staphylococcal skin infection, lymphopenia, low T cell number, absence of B cells, high number of NK cells, and a negligible response to mitogens. Since her older brother died as a result of SCID 2 years earlier, cord blood was harvested from a sister born 2 1/2 years earlier, who was normal and fully matched both by serology and molecular typing. In view of her clinical condition and in spite of a high number of NK cells with normal activity, HUCBT without preparative conditioning was performed. No G-CSF was administered. Engraftment with mixed chimerism was evident 3 weeks post transplantation. There were no peritransplantation complications. Eighteen months post transplantation, the girl is in excellent condition, blood counts are normal, T cell engraftment is complete, B cell engraftment is proceeding gradually, and the mitogen stimulation tests are normal. Due to the unique nature of HUCB hematopoietic cells, engraftment without conditioning may be possible in patients with SCID with fully matched donors. This is the first HUCBT performed without conditioning.

Female↗
PubMed1999

Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13.

Fechtner syndrome is an autosomal-dominant variant of Alport syndrome, manifested by nephritis, sensorineural hearing loss, cataract formation, macrothrombocytopenia, and polymorphonuclear inclusion bodies. As opposed to autosomal-recessive and X-linked Alport syndromes, which have been genetically well studied, the genetic basis of Fechtner syndrome remains elusive. We have mapped the disease-causing gene to the long arm of chromosome 22 in an extended Israeli family with Fechtner syndrome plus impaired liver functions and hypercholesterolemia in some individuals. Six markers from chromosome 22q yielded a LOD score >3.00. A maximum two-point LOD score of 7.02 was obtained with the marker D22S283 at a recombination fraction of 0. Recombination analysis placed the disease-causing gene in a 5.5-Mb interval between the markers D22S284 and D22S1167. No collagen genes or genes comprising the basement membrane have been mapped to this region.

Alleles↗
PubMed1998

Instability of dinucleotide repeats in Hodgkin's disease.

Tumorigenesis has been shown to proceed through a series of genetic alterations involving protooncogenes and tumor suppressor genes. However, the investigation of genomic instability of microsatellites has disclosed a new mechanism for human carcinogenesis, which is involved not only in hereditary nonpolyposis colon cancer (HNPCC) but in a number of other malignancies as well. To determine whether microsatellite instability is involved in Hodgkin's disease, we screened 16 such tumors using 7 microsatellite marker loci on 6 chromosome arms 4, 5, 9p, 9q, 11, 14, and 17. Using the polymerase chain reaction method, DNA samples from the tumors and from normal peripheral blood leukocytes from each patient were compared for the allelic pattern produced at each locus. Five cases of genomic instability were identified, suggesting that this mechanism is relevant to the pathogenesis of HD.

Chromosomes, Human↗
PubMed1998

Early fulminant leukaemia post autologous bone marrow transplantation in non-Hodgkin's lymphoma patients.

Although autologous bone marrow transplantation (ABMT) is a curative option for about 50% of the patients with progressive or relapsing lymphomas, considerable concern has been raised recently over the emerging rates of secondary malignancies following ABMT. A 15% cumulative incidence of myelodysplasia 5 years after BMT is of major concern. We hereby describe a unique form of leukaemia occurring 4-6 weeks post ABMT for non-Hodgkin's lymphoma patients. The possible etiology for this phenomenon as well as its relation to the classical MDS post ABMT is discussed.

Acute Disease↗
PubMed1998

Involved field radiation post autologous stem cell transplantation in lymphoma patients is associated with major haematological toxicities.

Irradiation is known to cause temporary to permanent marrow aplasia in cancer patients when administered as a sole therapy or in combination with chemotherapy. Until now, no studies have been carried out evaluating the haematological toxicities of involved field radiation administered post autologous stem cell transplantation (ASCT). We assessed bone marrow (BM) toxicity in 93 patients who received involved field radiation post ASCT (non-Hodgkin's lymphoma 21, Hodgkin's disease 7, breast cancer 15, and other solid tumours 50. Severe BM toxicity, with grade IV neutropenia, and/or thrombocytopenia, and/or anaemia necessitating interruption of radiotherapy for more than a week, was observed in 11 patients (malignant lymphoma-8 of which 7 were NHL, and 1 HD, breast cancer-1, Wilm's tumour-1, Ewing's sarcoma-1). Patients with malignant lymphoma were at higher risk of developing post ASCT radiation-induced cytopenias than patients with breast cancer or solid tumours, 28% vs 4.5%, respectively (P < 0.05). Of the 11 patients, 7 developed bacterial sepsis and 10 were hospitalised. The radiation-induced cytopenia patients necessitated platelets and red blood cell transfusions, interrupting the course of irradiation. Of the patients suffering from non-Hodgkin's lymphoma, 8/14 (57%) of those who received conventional courses of radiotherapy relapsed compared to 6/7 (86%) of those who received interrupted radiotherapy (P < 0.05). The most appropriate timing for radiation in malignant lymphoma patients who are scheduled for ASCT, as well as the protective role of haematopoietic growth factors like erythropoietin and Granulocyte (G) or Granulocyte-Monocyte (GM), colony stimulating factors (CSF) and others, are discussed.

Adult↗
PubMed1998

Effect of Temperature on Adhesion of Vibrio Strain AK-1 to Oculina patagonica and on Coral Bleaching.

Laboratory aquarium experiments demonstrated that Vibrio strain AK-1 caused rapid and extensive bleaching of the coral Oculina patagonica at 29 degrees C, slower and less-complete bleaching at 23 degrees C, and no bleaching at 16 degrees C. At 29 degrees C, the application of approximately 100 Vibrio strain AK-1 cells directly onto the coral caused 50 and 83% bleaching after 10 and 20 days, respectively. At 16 degrees C, there was no bleaching, even with an initial inoculum of 1.2 x 10 bacteria. To begin to understand the effect of seawater temperature on bleaching of O. patagonica by Vibrio strain AK-1, adhesion of the bacteria to the coral as a function of temperature was studied. Inoculation of 10Vibrio strain AK-1 organisms into flasks containing 20 ml of seawater at 25 degrees C and a fragment of O. patagonica resulted in net levels of bacterial adhesion to the coral of 45, 78, and 84% after 2, 6, and 8 h, respectively. The adhesion was inhibited 65% by 0.001% d-galactose and 94% by 0.001% methyl-beta-d-galactopyranoside (beta-M-Gal). After the incubation of Vibrio strain AK-1 with the coral for 6 h, 42% of the input bacteria were released from the coral with 0.01% beta-M-Gal, compared to less than 0.2% when beta-M-Gal was present during the adhesion step. Adhesion did not occur when Vibrio strain AK-1 was grown at 16 degrees C, regardless of whether the corals were maintained at 16 or 25 degrees C, whereas bacteria grown at 25 degrees C adhered to corals maintained at 16 or 25 degrees C. Bacteria grown at 25 degrees C adhered avidly to Sepharose beads containing covalently bound beta-d-galactopyranoside but failed to bind if grown at 16 degrees C. These data suggest that elevated seawater temperatures may cause coral bleaching by allowing for the expression of adhesin genes of Vibrio strain AK-1.

Journal Article↗
PubMed1998

The implications of granulocyte-monocyte colony-stimulating factor (GM-CSF) in cytotoxicity of bone marrow transplantation.

One of the major obstacles to the successful outcome of autologous bone marrow transplantation (ABMT) is the high relapse rate, which is most likely due to the lack of a graft-versus-tumor effect. The amplification of cell-mediated effector mechanisms against residual tumor cells is one of the ways to reduce relapse rates post ABMT at the stage of minimal residual disease. Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a key cytokine that plays a major role in cytotoxicity and in the activation pathways of monocytes, macrophages, dendritic cells and tumor-infiltrating lymphocytes. Therefore it may be used for manipulating the immune system to fight against cancer. The activities of GM-CSF on monocytes-macrophages, dendritic cells and recruited components of the immune system are described in the context of the development of improved strategies for conferring enhanced resistance to a tumor-bearing host following autologous or allogeneic bone marrow transplants.

Animals↗
PubMed1997

Human umbilical cord blood myeloid progenitor cells are relatively chemoresistant: a potential model for autologous transplantations in HIV-infected newborns.

Vertical transmission from mother to child occurs in 15-39% of women infected with the human immunodeficiency virus (HIV). Stem cell transplantation has recently been suggested as a potential therapy for patients with HIV infection. We have examined the possible advantages of human cord blood (HUCB) stem cells over bone marrow (BM) stem cells in the treatment of HIV-infected newborns. HUCB myeloid progenitors were found to be statistically more resistant to interferon-alpha (IFN-alpha), cytarabine (ARA-C), and eilatin than BM myeloid progenitor cells grown with IL-3 (P < 0.05). HUCB treated with IFN-alpha, ARA-C, and eilatin demonstrated a significantly higher capacity for self-renewal manifested by delta assay following 7 days in liquid culture. We, therefore, suggest that HUCB purged by anti-HIV drugs may be a source for autologous transplantation in HIV-infected newborns.

Antiviral Agents↗
PubMed1997

Central nervous system involvement at diagnosis in a case of pediatric CD30+ anaplastic large cell lymphoma.

Central nervous system (CNS) involvement in Ki-1/CD30 lymphoma is extremely rare, in contrast to the frequent involvement in other types of pediatric non-Hodgkin's lymphoma. No mechanism has yet been proposed to explain the sparing of the blood brain barrier in Ki-1/lymphoma. We present a 2-year-old boy who was admitted to the Department of Pediatric Hemato-Oncology due to lethargy, progressive breathing difficulties, massive diffuse lymphadenopathy, hepatosplenomegaly, and ichthyosis-like skin involvement with epidermolysis. A lymph node biopsy was compatible with Ki-1/CD30 anaplastic large cell lymphoma (ALCL). Bone marrow aspirate and biopsy demonstrated reactive hyperplasia. Cytogenetic analysis displayed hyperdiploid cells with 1p(-) in most cells. Cerebrospinal fluid examination showed pleocytosis with CD30+ cells. Possible mechanisms which could enable CNS involvement in this unusual case are discussed.

Central Nervous System Neoplasms↗
PubMed1997

The putative role of arylsulfatase in interleukin-2-mediated cytotoxicity and interleukin-7-mediated bactericidal activity of natural killer cells.

We have examined the cytolytic and bactericidal activity of resting and cytokine-stimulated natural-killer (NK) cells against K562 and Daudi cell lines and Escherichia coli, respectively. Unstimulated NK cells showed considerable cytolytic activity against K562 (64 +/- 4%) and relatively low activity against the Daudi cell lines (22 +/- 9%). Pretreatment of NK cells with the arylsulfatase (AS) type-II-specific inhibitor NaH2PO4 reduced cytotoxicity towards K562 and Daudi 1.3- and 2.9-fold (p < 0.05; n = 12), respectively, indicating that AS participates in NK-mediated cytotoxicity. Interleukin-2 (IL-2) (200 units/ml) caused a 1.3- and 3.5-fold (p < 0.5; n = 12) enhancement of NK cytotoxic activity against K562 and Daudi, respectively. Pretreatment of these cells with the AS type-II-specific inhibitor NaH2PO4 reduced cytotoxicity 1.1-fold towards K562 (p < 0.05; n = 12) and 1.2-fold towards Daudi (p > 0.05; n = 12) indicating that AS does not participate in IL-2-mediated NK cytolytic activity against these cell lines. IL-7 (3 units/ml) did not cause any enhancement of NK cytolytic activity. Unstimulated NK cells showed considerable bactericidal activity against E. coli (23 +/- 4%). Incubation of resting NK cells with NaH2PO4 reduced the bactericidal effect only by 1.09-fold (p > 0.05; n = 12), indicating that AS does not mediate this effect. IL-2 (200 units/ml) and IL-7 (3 units/ml) enhanced the bactericidal activity 1.5- and 2.2-fold, respectively (p < 0.05; n = 12). This effect was not influenced by incubation of IL-2-stimulated cells with NaH2PO4, indicating that AS does not participate in the IL-2-mediated NK bactericidal effect. IL-2 seems to exert its stimulatory effect upon NK-mediated bactericidal activity by a different, non-AS-dependent mechanism. However, incubation of IL-7-stimulated NK cells with NaH2PO4 reduced the NK bactericidal effect by 1.2-fold (p < 0.05; n = 12), indicating that AS may have a role in this reaction. These data can be further confirmed by detection of AS through degranulation of NK cells, showing that IL-2 induced only mild degranulation of resting and f-MLP-stimulated NK cells (26 +/- 1% vs 22 +/- 2% and 31 +/- 2% vs 29 +/- 2, respectively) (p > 0.05; n = 8). In contrast, IL-7 showed significant enhancement of AS release in resting or f-MLP-induced NK cells (36 +/- 3% vs 22 +/- 2% and 49 +/- 3% vs 29 +/- 2%, respectively) (p < 0.05; n = 8).

Arylsulfatases↗
PubMed1997

Invasive fungal infections in lymphoma patients receiving immunotherapy following autologous bone marrow transplantation (ABMT).

Invasive fungal infections are quite rare (1-5%) following conventional ABMT for malignant lymphoma. Two high-risk lymphoma patients (one non-Hodgkin's lymphoma (NHL) and one Hodgkin's disease) underwent ABMT followed by immunotherapy as part of an experimental therapy given to 12 lymphoma patients aiming to prevent relapse following transplantation. The post-immunotherapy course in both patients was complicated by invasive fungal infections (pulmonary mucormycosis and generalized aspergillosis). The association between invasive fungal infection and immunotherapy following ABMT for malignant lymphoma patients is discussed.

Adult↗
PubMed1997

Massive pericardial effusion complicating the course of chronic graft-versus-host disease (cGVHD) in a child with acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

The pathogenesis and clinical features of chronic graft-versus-host disease (cGVHD) resemble those of several autoimmune diseases, as evidenced by frequent dermal, hepatic, occular, oral, pulmonary, gastrointestinal and neuromuscular involvement. Serosal involvement, however, has only rarely been reported and most of the existing accounts are historical. We describe a boy transplanted in third CR of CALLA-positive ALL from his HLA-identical sister who developed cGVHD, which was complicated by a huge pericardial effusion as a part of severe polyserositis including pleural effusion, ascites, and polyarthritis. The patient shared the HLA antigens HLA-A2, B51, and DQW6 which are associated with autoimmune diseases.

Bone Marrow Transplantation↗
PubMed1997

Bilateral femoral stress fractures in a child due to in-line (roller) skating.

We report a child who presented with a limp following 6 weeks of strenuous roller skating. Directed X-rays on admission were normal but a 99mTc-methylene diphosphanate bone scan demonstrated increased uptake in the mid-thirds of the femurs compatible with grade IV stress fracture. Immediate abstention from roller skating for 5 weeks resulted in a complete cure. The "new" side effect of this increasingly popular sport is discussed with regard to paediatric stress fractures and to other roller skating-associated injuries.

Child, Preschool↗
PubMed1997

Soluble interferon-gamma receptor and interferon-gamma in patients undergoing allogeneic bone marrow transplantation for hematological malignancies.

Interferon-gamma (IFN-gamma) is known to be involved in graft rejection of solid organs and acute graft-versus-host disease (GVHD). Its role, and especially that of soluble IFN-gamma receptor (sIFN-gamma R), in bone marrow transplantation (BMT) has not been established. We evaluated the sera of 27 patients following BMT. Fourteen of them underwent uneventful BMT, whereas 13 developed transplant-related complications, including acute GVHD (n = 5), early rejection (n = 4), or relapse of basic disease (n = 4). Soluble IFN-gamma R and IFN levels were evaluated at day -10 (preconditioning), day 0 (day of BMT), day of engraftment, and during BMT-related complications using sIFN-gamma R-specific monoclonal antibodies (McAB) followed by double-sandwich ELISA, and a sensitive radioimmunoassay respectively. In normal controls (n = 80) sIFN-gamma R and IFN-gamma levels in the sera were 0.5 +/- 0.05 and 0.3 +/- 0.04 ng/ml respectively. Soluble IFN-gamma R levels increased in direct correlation with engraftment (0.63 +/- 0.11 ng/ml at the day of BMT to 1.43 +/- 0.16 ng/ml at the day of engraftment; n = 14; P < 0.001). IFN-gamma levels increased in direct correlation with engraftment (0.37 +/- 0.03 ng/ml at the day of BMT to 5.69 +/- 1.64 ng/ml at the day of engraftment; n = 14; P < 0.001). In five patients with GVHD sIFN-gamma R levels increased from 0.43 +/- 0.19 ng/ml at the day of BMT to 1.73 +/- 0.17 ng/ml (P < 0.004) at the time of GVHD. Similarly, IFN-gamma levels increased from 0.43 +/- 0.08 ng/ml at the day of BMT to 3.03 +/- 0.5 ng/ml at the time of GVHD (P < 0.05). Both graft rejection and early relapse were associated with an elevation of IFN-gamma levels. In short, both s-IFN-gamma R and IFN-gamma were found to be significantly elevated during engraftment and GVHD. Hence these cytokines may be used as a tool for assessing engraftment and AGVHD.

Adolescent↗
PubMed1996

Soluble interleukin-6 receptors in hematology patients undergoing bone marrow transplantation.

Soluble interleukin-6 receptor (sIL-6R) has previously been shown to potentiate the activity of interleukin (IL)-6, which may display antitumor activity. We evaluated sIL-6R and IL-6 levels in the sera of 24 patients following transplantation (allogeneic, n=17; autologous, n=7). Five patients developed acute graft-versus-host disease (AGVHD), three had early graft rejection, and three had an early relapse following bone marrow transplantation (BMT). Soluble IL-6R levels were evaluated at day - 10, day 0, day of engraftment, and during BMT-related complications, using IL-6R-specific monoclonal antibodies (mAb) and double-sandwich ELISA. In normal controls, sIL-6R and IL-6 levels were 20+/-3 ng/ml and 0.01+/-0.005 ng/ml, respectively. Soluble IL-6R levels increased in direct correlation with engraftment in the uneventful allogeneic transplants (17.7+/-2.1 ng/ml at day 0 to 49.7+/-2.6 ng/ml at day of engraftment, n=6, P<0.05) as well as in the autologous transplants (26.8+/-2.82 at day 0 to 66.4+/-12.9 at day of engraftment, n=5, P=0.01). In contrast, IL-6 levels declined with time during the conditioning period and showed only a modest elevation following BMT. Increased levels of sIL-6R and IL-6 were found in the patients who developed AGVHD (23.8+/-4.2 and 0+/-0 ng/ml at day 0 to 79+/-6.9 and 0.26+/-0.04 ng/ml, respectively, at time of AGVHD, n=5, P=0.01). No correlation was found between the severity of AGVHD and sIL-6R levels. In the three patients with early relapse, sIL-6R levels increased from 30+/-0 ng/ml at day 0 to 90 ng/ml (P=0.05) and IL-6 levels increased from 0 to 0.16+/-0 ng/ml, respectively. The mean elevation of sIL-6R in the patients with early relapse and AGVHD was significantly higher than the mean elevation in the patients with the relatively smooth engraftment (P<0.05). Contrary to these findings, in the three patients with graft rejection, sIL-6R levels decreased while IL-6 was found to be elevated. Basic disease, conditioning regimen, type of transplant, GVHD propylaxis, and T cell depletion had no effect on sIL-6R or IL-6 levels. In summary, sIL-6R levels positively correlated with engraftment. Both sIL-6R and IL-6 levels were found to be significantly elevated in patients who developed AGVHD or early relapse following BMT. Therefore, the sIL-6R level may be used as a tool for assessing engraftment and transplant-related complications following BMT.

Acute Disease↗