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Biomedical subjects

B Finkel

Publications and source records attributed to B Finkel.

11 recordsLinked to original sources
PubMed1994

[Immunogenicity and stability of an aluminum-free liposomal hepatitis A vaccine (Epaxal Berna)].

The high immunogenicity of the liposomal hepatitis A vaccine (Epaxal Berna) after a single dose and after a booster dose one year later has been confirmed in several studies with healthy adult volunteers: 95-100% and 96-100% seroconversion (> or = 20 mIE/ml) after 1 and 12 months respectively, as well as a booster effect in 100% of the cases after revaccination. The tolerability of this new, alum-free vaccine has been excellent with 6-25% local and 0-13% mild systemic reactions after a dose of 0.5 ml. Stability testing with and without detergent indicated partial internalization of the hepatitis A virions in the phospholipid bilayer of the liposome vesicles with storage. Immunization of 10 healthy adult volunteers with vaccine stored for 32 months at 4 degrees C showed, however, that the duration of storage has no influence on immunogenicity and tolerability of the vaccine.

Adult↗
PubMed1994

Immunogenicity of new virosome influenza vaccine in elderly people.

The safety and immunogenicity of a new virosome influenza vaccine was compared to commercial whole-virus vaccine and subunit vaccine in elderly people. The virosome vaccine was made by extracting the haemagglutinin from influenza virus and incorporating it into the membrane of liposomes composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). 126 residents of a nursing home, aged 63-102, were randomised to receive one of the vaccines. All three were well tolerated and caused a significant rise in the geometric mean anti-haemagglutinin inhibiting (HAI) antibody titre to the 3 vaccine components (H1N1 Singapore, H3N2 Beijing, and B/Yamagata). The virosome formulation caused the highest geometric mean titres in addition to significantly (p = 0.039-0.0016) higher rates of more than four-fold or more titre rises to all 3 vaccine components. The percentage of those immunised who achieved protective levels of antibody (HAI > or = 40) was significantly (p = 0.035-0.0017) higher for the H1N1 and B/Yamagata strains following immunisation with virosome formulation. Participants with non-protective baseline titres to the H1N1 or B/Yamagata strains were more likely (p = 0.0049-0.006) to achieve protective levels of antibodies after immunisation with the virosome vaccine. Immunisation with the virosome formulation did not result in a significant rise in anti-PC or anti-PE antibodies.

Aged↗
PubMed1993

Effects of acute, low-dose UVB radiation on the induction of contact hypersensitivity to diphenylcyclopropenone in man.

Healthy volunteers (n = 14, age range 20-31 years, mean 23) were irradiated on the inside of the left forearm on four consecutive days with their individual minimal erythemal dose of ultraviolet B (UVB) prior to sensitization in the same skin area with a 2% solution of diphenylcyclopropenone (DPCP). The reaction patterns were compared with 14 alopecia areata patients (age range 16-69 years, mean 40) starting topical immunotherapy with DPCP, sensitized without prior UVB treatment. Primary allergic reactions occurred in ten volunteers and in four alopecia areata patients. Patch testing on the upper back with serial dilutions of DPCP (1% to 10(-8)%) showed minimal dermatitis-eliciting concentrations ranging from 1 to 10(-4)% (mean 0.19%) in the volunteers as compared with 10(-1) to 10(-8)% (mean 0.025%) in the alopecia areata patients. Two patterns were discernible within the volunteers with respect to the intensity of the primary allergic and elicitation reactions. Ten volunteers reacted in a similar way to the alopecia areata patients, whereas four probands demonstrated very high minimal dermatitis-eliciting concentrations and overall less severe reactions. The DPCP-specific T-cell response using blood macrophages and B lymphocytes as antigen-presenting cells was measured in an in vitro assay in two alopecia areata patients and two volunteers having similar skin reactions as well as in two volunteers with overall less severe skin reactions. B lymphocytes from the alopecia areata patients and the volunteers with similar skin reactions induced a significant DPCP-specific T-cell proliferation exceeding the responses obtained using macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

CA-15.3, TPA and MCA as markers for breast cancer.

Serum concentrations of CA-15.3, tissue polypeptide antigen (TPA) and mucinous-like carcinoma-associated antigen (MCA) were measured in 327 women: 81 controls, 93 patients with benign breast disease, 46 patients recently diagnosed with breast cancer and 107 patients during breast cancer follow-up. CA-15.3 was elevated in 16% of the controls, in 29% of the patients with benign breast disease, in 65% of the breast cancer patients and in 74% of the follow-up patients. TPA was elevated in 4%, 11%, 36% and 75%, respectively. The corresponding figures for MCA were 10%, 8%, 30% and 64%. The highest sensitivity for cancer detection (74%) was obtained with a combination of CA-15.3 and TPA, while the specificity of this panel was 75%. The negative predictive value of these combined tests was 93%. MCA scored lower values, being only 30% sensitive. The CA-15.3/TPA panel may increase sensitivity compared with single marker tests and provide additional information for clinical evaluation.

Antigens, Neoplasm↗
PubMed1986

Lymphoblastic transformation of myelodysplastic syndrome.

Acute myeloblastic leukemia occurs as a complication of myelodysplastic syndromes, but the appearance of an acute lymphoblastic leukemia (ALL) has only been reported once. We describe a case in which lymphoblastic transformation occurred in the setting of a dysmyelopoietic syndrome. This leukemia was characterized by lymphoid morphology, terminal deoxynucleotidyl transferase (TdT) positivity, cytogenetic abnormalities, and immunoglobulin gene rearrangements. The patient responded to conventional therapy for this leukemia (vincristine and prednisone). Our case supports the hypothesis of a common lymphohemopoietic progenitor and suggests that in vitro tests may help identify a subset of these patients and be important in selecting appropriate therapy.

Aged↗
PubMed1983

Increased adsorption of cytoplasmic proteins to the erythrocyte membrane in ATP-depleted normal and pyruvate kinase-deficient mature cells and reticulocytes.

How the metabolic defect of pyruvate kinase deficiency (PK(-)) accelerates red blood cell (RBC) destruction is not established, but may be related to RBC membrane abnormalities associated with altered cellular metabolism. Furthermore, it has been shown that PK(-) reticulocytes are especially sensitive to metabolic depletion. Therefore, we compared the membranes of reticulocyte-rich PK(-) RBC, both fresh and ATP depleted, with membranes of fresh and ATP depleted normal mature RBC and reticulocytes. There was no difference between the specific gravity (SG) of the membranes of normal mature RBC (SG 1.152 +/- 0.004) and membranes of reticulocyte-rich RBC from several anemias (SG 1.150 +/- 0.002). However, membranes from fresh, reticulocyte-rich PK(-) RBC were dense with SG of 1.165 +/- 0.004 which correlated with a corresponding increase of protein to lipid phosphorus ratio of 66 +/- 8 micrograms protein/micrograms lipid phosphorus (normal 52 +/- 6 micrograms/micrograms). The membrane density of PK(-) RBC was further increased when the PK(-) RBC ATP was depleted by anaerobic incubation (SG 1.188 +/- 0.004) or cyanide inhibition (SG 1.182 +/- 0.001). When ATP was depleted in normal RBC and in non-PK(-) reticulocytes, corresponding increases in membrane SG occurred. A distinctive 50,000 MW peptide is adsorbed from the cytoplasm to the membranes of reticulocytes (both normal and PK(-) when these cells were depleted of ATP. The increased membrane adsorption of cytoplasmic proteins by PK(-) RBC was not associated with increased RBC calcium uptake, sulfhydryl oxidation, or altered membrane protein phosphorylation. All the observed abnormalities of PK(-) RBC membranes could by reproduced by ATP depletion of reticulocyte-enriched non-PK(-) RBC.

Absorption↗
PubMed1980

Decreased survival in vivo of diamide-incubated dog erythrocytes. A model of oxidant-induced hemolysis.

Erythrocytes from patients with chronic hemolytic variants of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency have structural membrane protein abnormalities accompanied by decreased cell membrane deformability which we postulate represent the consequences of oxidant-induced membrane injury. To evaluate the pathophysiologic significance of oxidant-induced membrane injury, we studied the in vitro and in vivo effects of the thiol-oxidizing agent, diamide, on dog erythrocytes. In vitro incubation of dog erythrocytes with 0.4 mM diamide in Tris-buffered saline for 90 min at 37 degrees C resulted in depletion of GSH, formation of membrane polypeptide aggregates (440,000 and > 50,000,000 daltons) and decreased cell micropipette deformability, abnormalities similar to those observed in the erythrocytes of patients with chronic hemolytic variants of G-6-PD deficiency. In addition, diamide-incubated cells had increased viscosity and increased membrane specific gravity, but no change in ATP. Reinjection of 51Cr-labeled, diamide-incubated cells was followed by markedly shortened in vivo survival and splenic sequestration. Further incubation of diamide-incubated cells in 4 mM dithiothreitol reversed the membrane polypeptide aggregates, normalized micropipette deformability, decreased cell viscosity, prolonged in vivi survival, and decreased splenic sequestration. These studied demonstrate that diamide induces a partially reversible erythrocyte lesion which is a useful model of oxidant-induced membrane injury. They suggest that oxidant-induced erythrocyte membrane injury plays an important role in the pathophysiology of chronic hemolysis which accompanies some G-6-PD variants.

Adenosine Triphosphate↗
PubMed1977

Increased membrane binding of erythrocyte catalase in hereditary spherocytosis and in metabolically stressed normal cells.

Normal red blood cell (RBC) membranes were compared with (1) RBC membranes from six patients with hereditary spherocytosis (HS), (2) normal membranes after hemolysis of the RBC in the presence of calcium, or (3) normal membranes after incubation of RBC for 24 hr in phosphate-buffered saline containing calcium without added glucose. When compared with normal controls, polyacrylamide gel electrophoresis with sodium dodecyl sulfate (PAGE SDS) of all three preparations showed an increase in membrane binding of globin and protein band 4.5 (60,000 molecular weight). In an attempt to identify band 4.5, 14 enzymes were assayed in the RBC membranes. Of these, catalase and lactate dehydrogenase were increased in membranes from HS RBC and from normal cells exposed to calcium. Only catalase, however, was present in sufficient quantity and had the correct subunit molecular weight on PAGE SDS and calcium-dependent membrane binding to account for an appreciable portion of 4.5. Caralase was further identified with a component of band 4.5 by double immunodiffusion using a specific anti-catalase antibody.

Calcium↗
PubMed1976

Study of a kindred with hereditary spherocytosis and glyceraldehyde-3-phosphate dehydrogenase deficiency.

A patient with hereditary spherocytosis (HS) was found to have glyceraldehyde-3-phosphate dehydrogenase (G3PD) deficiency by electrophoresis of the isolated red cell membranes on polyacrylamide gels with sodium dodecyl sulfate (PAGE SDS) as demonstrated by a diminished band 6 (G3PD) and confirmed by specific enzyme assay. Thirteen members of his family were studied: four were normal, two had HS alone, three had G3PD deficiency alone, and four had both HS and G3PD deficiency. G3PD deficient kindred members were probably heterozygous, since their red cell enzyme, while qualitatively normal, was present in half normal amounts. The G3PD deficiency alone was asymptomatic, and there was no evidence that the combination of HS with G3PD deficiency increased the clinical severity of the disease. However, G3PD deficiency, when combined with HS, was associated with an increase in protein band 4.5 on PAGE SDS. This band was also increased by incubation of normal red cells without glucose, and appeared to be a protein absorbed to the membrane as a consequence of metabolic stress. Hence, red cells with the combined abnormalities of both HS and G3PD deficiency showed signs of the exceptional metabolic stress to which they were exposed.

Adult↗
PubMed1975

Bis-(N-maleimidomethyl) ether: an antisickling reagent.

The interaction of bis-(N-maleimidomethyl) ether with oxyhemoglobin results in covalent linkages of both maleimide groups, converting them to succinyl derivatives of beta93 Cys and beta97 His at their sulfhydryl and imidazolyl side chains, respectively. The resultant hemoglobin is stable, and reveals a left-shifted oxyhemoglobin equilibrium curve in which cooperativity is abolished. This reagent readily traverses the red cell membrane and prevents the sickling reaction upon deoxygenation. It appears to affect none of the activities of the red cell enzymes adversely, nor does it appear to affect the red cell membrane. Since there are several defined effects on the stereochemical status of the molecule conferred by interaction with bis-(N-maleimidomethyl) ether, the precise mechanism of the anitsickling effect remains to be elucidated. A more subtle perturberant will be required to specify a precise antisickling effect. By use of bis-(N-maleimidomethyl) ether a precise locus on the beta chain of human hemoglobin S can be perturbed to produce the desired effect.

Anemia, Sickle Cell↗