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Biomedical subjects

D Bron

Publications and source records attributed to D Bron.

At least 73 records · Page 4Linked to original sources
PubMed1990

Production of human monoclonal IgG antibodies reacting with cytomegalovirus (CMV).

A human monoclonal antibody (MoAb) reacting with cytomegalovirus (CMV) has been produced using somatic cell hybridization between Epstein-Barr virus (EBV) infected B lymphocytes and a human-mouse heteromyeloma cell line (SHM-D33). The hybrids were selected in HAT medium containing 5 x 10(-7) ouabain. The median level of Ig production was 5 (0.1-20) micrograms/10(6) cells/day. One selected hybridoma (IB-8E9H5) has been maintained in continuous culture for more than 30 months with a stable IgG2, lambda production. Molecular hybridization using EBV-specific probes demonstrate that our hybrids have lost the IR-1 EBV sequence during fusion. Unexpectedly, these blotting experiments revealed the presence of multiple EBNA-1 sequences dispersed among the genomic DNA of the SHM-D33 cell line. Screening for anti-CMV specificity was performed by ELISA and confirmed by immunofluorescence staining. Thus far, three CMV reference strains and 14 local strains are stained by the MoAb as early as 3 h after CMV infection of human fibroblasts, apparently through the recognition of a nuclear viral antigen of 67 kDa. In conclusion, this technique permits (a) the removal of the EBV genome contained in the lymphoblastoid parental cell line and (b) the production of human anti-CMV MoAb with potential applications in the prevention of life threatening CMV infections.

Antibodies, Monoclonal↗
PubMed1990

Inhibitory effects of potent inhibitors of human immunodeficiency virus and cytomegalovirus on the growth of human granulocyte-macrophage progenitor cells in vitro.

Phosphonoformate, ganciclovir, zidovudine and the novel acyclic nucleotide analogues (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were evaluated for their inhibitory effect on colony forming unit formation by human granulocyte-macrophage progenitor cells (obtained from 11 healthy volunteers) in vitro. The 50% inhibitory dose of zidovudine, (S)-HPMPA, (S)-HPMPC, ganciclovir and phosphonoformate were 10.61, 16.55, 80.88, 41.02 and 668.64 microM, respectively, when the median-effect principle was applied. The bone marrow toxicity of zidovudine used at a low concentration (3.74 microM) was significantly decreased if the drug was combined with (S)-HPMPA, (S)-HPMPC or ganciclovir. If used at higher concentrations (74.90 microM), zidovudine showed increased myelotoxicity in the presence of (S)-HPMPA and ganciclovir, but not (S)-HPMPC.

Adenine↗
PubMed1990

Ceftazidime plus teicoplanin versus ceftazidime plus amikacin as empiric therapy for fever in cancer patients with granulocytopenia.

In a prospective randomized study, 100 episodes of fever (greater than 38 degrees C) and granulocytopenia (less than 1000/microliters) in cancer patients were empirically treated with ceftazidime (2 g every 8 h) plus teicoplanin (400 mg every 8 h on day 1; 400 mg every day thereafter) or ceftazidime (2 g every 8 h) plus amikacin (500 mg every 8 h). Bacteraemia, clinically documented infection and possible infection were documented in seven, 11 and 19 patients treated with ceftazidime plus teicoplanin and in 11, four and 17 patients treated with ceftazidime plus amikacin. Overall, the response rate was similar in the two groups of patients as was the need for treatment modifications and the rate of death. For documented Gram-positive bacteraemia, the response rate was 2/5 patients treated with ceftazidime plus teicoplanin and 2/7 with ceftazidime plus amikacin; for documented Gram-negative bacteraemia, the response rate was 1/2 and 3/4 patients respectively. No breakthrough bacteraemia was observed. Tolerance was excellent, although renal toxicity (elevation of serum creatinine) was observed in three patients treated with ceftazidime plus teicoplanin and in none allocated to ceftazidime plus amikacin.

Adult↗
PubMed1990

Influence of recombinant alpha and gamma interferons on the in vitro proliferation of myeloid and leukemic progenitors.

We have compared the effect of alpha 2-C and gamma recombinant interferons (rIFNs) on normal myeloid progenitors (N-CFU-GM), chronic myeloid leukemia (CML) progenitors (CML-CFU-GM) and leukemic progenitors (L-CFU) of acute non-lymphoblastic leukemia (ANLL) patients. Within 14 days of continuous exposure in culture, a dose-dependent inhibition of CFU-GM was seen for most normal subjects. Resistance to rIFNs was frequent in leukemic patients and even more in acute leukemia than in CML. Stimulation of clonogenic cell growth was seen for a minority of leukemic patients. When only the sensitive cases were considered, no difference in sensitivity was noticed between normal, CML and ANLL patients. A good correlation was observed between the activity or the lack of activity of alpha and gamma rIFNs.

Bone Marrow↗
PubMed1989

[Adoptive immunotherapy with interleukin 2. Initial results of a pilot study in 6 cancer patients].

Adoptive immunotherapy of cancer consists of using interleukin-2 to induce the formation of lymphokine-activated killer (LAK) cells which are toxic to tumoral cells. Six patients, 3 with hypernephroma and 3 with melanoma, were treated with interleukin-2. Drug toxicity consisted of capillary leakage syndrome in one case and reversible renal impairment in another. One patient showed an objective response; transient subjective improvement was observed in all patients.

Acute Kidney Injury↗
PubMed1989

Successful treatment with liposomal amphotericin B in two patients with persisting fungemia.

Two granulocytopenic patients in whom fungemia persisted despite therapy with deoxycholate amphotericin B were subsequently successfully treated by daily intravenous administration of amphotericin B entrapped in sonicated liposomes made of egg yolk lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. High serum concentrations of amphotericin B could be maintained in both patients during therapy with liposomal amphotericin B and were associated with high in vitro antifungal activity. Liposomal amphotericin B was tolerated much better than the deoxycholate preparation. These findings suggest that the liposomal amphotericin B preparation is superior in the treatment of fungemia in granulocytopenic patients, and that randomized trials are warranted.

Agranulocytosis↗
PubMed1989

Immunoprophylaxis of cytomegalovirus infections in transplanted patients.

Cytomegalovirus causes severe infections in immunosuppressed patients and anti-viral treatments remain unsatisfactory. In an attempt to prevent life-threatening CMV infections, immunoprophylaxis using hyperimmune immunoglobulins has been studied but led to conflicting results in the literature. The role of passive immunization in allogeneic marrow and renal transplant patients is discussed.

Bone Marrow Transplantation↗
PubMed1989

Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL-2 [ala-125]) and lymphokine-activated killer cells in patients with metastatic solid tumors.

The tolerance of a recombinant human interleukin-2 (rIL-2, r-met Hu IL-2 [ala-125], Ortho Pharmaceutical) and its antitumor effectiveness in combination with lymphokineactivated killer (LAK) cells was examined in 26 patients with metastatic solid tumors, including 14 renal cell carcinomas, seven melanomas, three extragonadal germ cell tumors refractory to chemotherapy and two colon carcinomas. rIL-2 was administered as a bolus at 30,000 U/kg every 8 h on days 1-5 and days 12-19. Leukapheresis was done on days 8-12, lymphocytes were incubated with rIL-2 for 3 or 4 days in vitro and reinfused on days 12, 13 and 15. The mean number of reinfused cells was 5.1 x 10(10) per patient. IL-2 dose and schedule were adjusted according to toxicity. Patients received a median of 100% (range 87-100%) of planned rIL-2 on days 1-5 and a median of 71% (range 13-100%) on days 12-19. Capillary leak syndrome with hypotension and impaired renal function and CNS toxicity were the major reasons for dose modification. Patients with renal cell carcinoma, most of whom underwent a prior nephrectomy, had a reduced tolerance to rIL-2. Partial responses were documented in three renal cell carcinomas and one melanoma. The median response duration was 5.5 (range 1-6) months.

Adult↗
PubMed1989

Controversies in the management of gastrointestinal non-Hodgkin's lymphomas.

Although more than a thousand GI non-Hodgkin's lymphomas have been reported, the literature does not indicate a clear optimal therapeutic approach. This is primarily due to histological confusion and to the absence of uniform staging procedures and therapeutic modalities. This overview attempts to summarize controversies in the multidisciplinary approach to GI non-Hodgkin's lymphomas and to introduce a European multicentric prospective randomized study for the treatment of this rare disease.

Combined Modality Therapy↗
PubMed1988

Multiple organ failure during interleukin-2 administration and LAK cells infusion.

Adoptive immunotherapy is a new promising treatment for cancer but is associated with severe toxicity mainly related to a capillary leak syndrome. We report the case of a patient with metastatic hypernephroma, who had many complications such as coma, renal failure, pulmonary edema, life-threatening acidosis, cardiac arrhythmias and venous thrombosis. Critical care specialists should be aware of this type of cancer therapy because of multiple side effects requiring ICU supportive care.

Bone Neoplasms↗
PubMed1988

Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia.

One hundred nineteen sera from patients with various lymphoproliferative diseases and normal sera were tested by a solid-phase radioimmunoassay (RIA) for their content in IgE-binding factor (IgE-BF), a soluble glycoprotein binding to IgE and derived from low-affinity IgE receptors (Fc epsilon R). Fc epsilon R, recently identified as CD23, are known to be expressed on the surface of B cells at the intermediate stage of differentiation. The results indicate that in all cases of chronic lymphocytic leukemia (CLL) tested (n = 40), IgE-BF levels (45 to 8,656 U/mL) were 3-fold to 500-fold higher than in 24 controls (15.5 +/- 2 U/mL). With a few exceptions, serum IgE-BF levels could differentiate patients with CLL from those with other leukemias or lymphomas. In vitro studies indicated that B lymphocytes isolated from CLL patients produced 8 to 50 times more IgE-BF than did normal B cells (P less than 0.001). IgE-BF level was correlated with the Rai stage of the disease (P = 0.002) and the lymphocyte count (P = 0.041). IgE-BF was purified to homogeneity from one CLL serum sample by a combination of affinity chromatography and reverse-phase high-performance liquid chromatography (HPLC). this IgE-BF proved identical to IgE-BF isolated from the culture supernatant of RPMI 8866 cells, a B lymphoblastoid cell line bearing Fc epsilon R and secreting IgE-BF. Indeed, the two molecules had the same mol wt (25 to 27 kd), the same isoelectric point, and the same tryptic map. We suggest that determination of serum IgE-BF might prove useful for clinical monitoring of CLL.

B-Lymphocytes↗