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J K Weltman

Publications and source records attributed to J K Weltman.

At least 19 recordsLinked to original sources
PubMed2000

IL-5: biology and potential therapeutic applications.

IL-5 is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of Th-2 cells leads to the production of IL-5. The pro-eosinophilic effects of IL-5 include: (1) enhanced replication and differentiation of eosinophilic myelocytes; (2) enhanced degranulation of eosinophils; (3) prolonged survival time of eosinophils: and (4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (IL-5R) that are expressed on the eosinophil cell membrane. Intracellular signalling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45 kDa glycoprotein consisting of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. Anti-IL-5 reagents have the potential to suppress IL-5 activity without the side effects of glucocorticoids. Studies using monoclonal antibodies (mAbs) against IL-5 have established the feasibility of suppressing eosinophilic inflammation by specifically blocking IL-5 activity. Studies with antisense IL-5 are beginning to provide the basis for non-glucocorticoid, sequence-specific oligonucleotide inhibitors of IL-5. Research has begun on the development of mAbs and antisense oligonucleotide inhibitors of IL-5 that can be inhaled and applied topically.

Chromosome Mapping↗
PubMed1995

Maleimide-mediated protein conjugates of a nucleoside triphosphate gamma-S and an internucleotide phosphorothioate diester.

The purpose of this study was to determine whether the gamma-S of nucleoside thiotriphosphates and the non-bridging sulfur of internucleotide phosphorothioate diesters possess sufficient thiol character to form adducts with maleimides. Adenosine triphosphate gamma-S (ATPS) and thymidyl-PS-thymidine (TPST) were each reacted with the reporter molecule N-1 pyrene maleimide (PM) and the fluorescence intensity was recorded. The observed reactivity of the phosphorothioate nucleotides towards maleimide was used as a basis for preparing covalent protein-nucleotide conjugates of ATPS and of the internucleotide phosphorothioate diester, deoxyadenylyl-PS-deoxy-adenylyl-PS-deoxyadenosine (dA3(PS)2). The absorbance spectra of bovine serum albumin (BSA) conjugates of ATPS and of dA3(PS)2 showed the formation of protein-nucleotide conjugates, with absorbance maxima near 260 nm. The degree of conjugation was 1.69 nucleotides (nt)/BSA molecule for ATPS and 0.44 nt/BSA molecule for dA3(PS)2. The extent of conjugation of the gamma-S of the nucleoside thiotriphosphate and of the non-bridging sulfur of the internucleotide phosphorothioate diester with maleimide-derivatized protein agreed with their relative reactivity towards PM. Both the gamma-S of the nucleoside thiotriphosphate and the internucleotide phosphorothioate diester were found to possess sufficient thiol character to permit formation of maleimide-mediated protein conjugates.

Adenosine Triphosphate↗
PubMed1992

Internalization of monoclonal antibodies selected for immunotoxin activity against small-cell lung cancer.

Two hybridomas producing MOABs with anti-SCLC activity were selected for immunotoxin activity by an indirect screen and were twice cloned. Binding activity of the MOABs to SCLC cells was demonstrated by immunoperoxidase activity, which could be blocked by streptavidin. The MOABs mediated the internalization of a biotinylated Fab' anti-mouse Ig marker at 37 degrees C. Internalization of the biotinylated marker by the SCLC target cells resulted in protection of the marker from streptavidin-blocking. These results show that MOABs selected for immunotoxin activity against SCLC can mediate internalization of an antibody fragment with a mass about 50% greater than that of the toxin. MOABs selected for immunotoxin activity may be useful for delivering agents other than toxins to the inside of SCLC cells.

Antibodies, Monoclonal↗
PubMed1987

Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer.

For the first time, a screening procedure for antitumor monoclonal antibodies (MOABs) has been developed in which the ability of MOABs to mediate the indirect action of another immunotoxin is the primary criterion for selection of hybridomas for expansion and cloning. Use of the indirect immunotoxin makes it possible to screen MOABs for cytotoxic potential without the necessity of covalently coupling toxin to each individual MOAB. Hybridomas derived from spleens of immunized mice were screened for the synthesis of monoclonal antibodies able to participate in the delivery of a pharmacologically active, indirect immunotoxin conjugate to H69 lung cancer cells. The indirect immunotoxin conjugate was goat anti-mouse immunoglobulin disulfide linked to pokeweed antiviral protein. There was no correlation between the results of the screening with the indirect immunotoxin and an enzyme-linked immunosorbent assay screen for binding of MOAB to tumor cell membranes. An indirect immunotoxin prepared from Fab' fragments of goat anti-mouse immunoglobulin was also effective as an indirect immunotoxin conjugate. Each screening of more than 300 hybridomas was performed in 3 days. The indirect immunotoxin screen detected antitumor MOABs which were not detected by the conventional enzyme-linked immunosorbent assay method. A MOAB selected by the indirect immunotoxin screen was conjugated to pokeweed antiviral protein; the conjugate mediated immunocytotoxicity in a standard direct toxicity assay.

Animals↗
PubMed1981

An analysis of allergy, immunoglobulin E, and diagnostic skin tests in schistosomiasis.

Factors governing the sensitization or desensitization of basophils and mast cells are discussed. Mathematical models are proposed which illustrate the effects of rising or falling specific or non-specific IgE titres on the tendency of these cells to degranulate. The models presented are consistent with the hypothesis that fine-tuning of the degranulatory event is achieved by one or more of the following mechanisms: alteration of the number of IgE receptors on the mast cell membrane; displacement of specific anti-schistosomal IgE by anti-other-IgE molecules; clipping or otherwise inactivating mast cell-fixed specific IgE receptor sites so as to render these incapable of binding antigen. Mechanisms proposed may explain how a mast cell population may evolve from highly sensitive to non-reactive allergic states during early and/or chronic periods of schistosomiasis, only to revert to highly sensitive states once again, after the disease has been overcome.

Hypersensitivity↗
PubMed1980

Diffusion control of the binding of carcinoembryonic antigen (CEA) with insoluble anti-CEA antibody.

Analysis of the kinetics of CEA binding to rabbit anti-CEA antibody insolubilized on filter paper discs provided six lines of evidence indicating diffusion control of this reaction: 1) The observed forward rate constant, k1obs, decreased when solvent viscosity was increased with sucrose or Ficoll. 2) k1obs per receptor site increased from 1.2 x 10(4) M-1 sec-1 to 2.6 x 10(4) M-1 sec-1 as receptor site density on immunosorbent discs decreased from 5.2 x 10(-13) to 2.1 x 10(-13) moles/disc. 3) Stirring the reacting mixture of CEA and insoluble anti-CEA increased k1obs from 1.2 x 10(4) M-1 sec-1 to 3.4 x 10(4) M-1 sec-1. 4) The activation energy for CEA-insoluble anti-CEA binding was indistinguishable (p greater than 0.1 by t-test) from 4.1 Kcal/mole expected for diffusion controlled reactions. 5) Bimolecular reaction theory predicted a diffusion limited forward rate constant, k1max, for CEA binding to insoluble anti-CEA, which was consistent with our observed k1 of 1.2 x 10(4) M-1 sec-1. 6) k1obs for CEA binding to soluble rabbit anti-CEA antibody was 6.4 x 10(4) M-1 sec-1, 5 times faster than the k1obs of the heterogeneous phase reaction for receptor site density of 5.2 x 10(-13) moles/disc. Diffusion control of ligand binding to insoluble receptors, as exemplified by the CEA-insoluble anti-CEA model system, may be a very general biologic phenomenon.

Animals↗
PubMed1979

Adverse reactions to cromolyn.

The frequency of adverse reactions (dermatitis, myositis, and gastroenteritis) to cromolyn sodium in asthmatic patients was 2% (B/375). Reactions were non-life-threatening and completely reversible. Immunologic evaluations, including skin and serum tests for immediate and delayed reactivity, all were negative. Adverse reactions to cromolyn do not appear to be based on an immunologic mechanism. Cromolyn appears to be a safe drug for the treatment of asthma.

Adolescent↗
PubMed1979

Species specificity of the immediate hypersensitivity to schistosomal proteolytic enzyme.

An acidic proteolytic enzyme which digests host haemoglobin can be isolated and purified from schistosomes. This small glycoprotein is an allergen which sensitizes the host, as shown by immediate hypersensitivity reactions. These are specific for either Schistosoma haematobium or S. mansoni and can be demonstrated by mast cell degranulation in mice or by intradermal skin tests in monkeys. Although high levels of total IgE may be found in acute and chronic schistosomiasis, there was no evident relationship between the worm burden in monkeys and immediate hypersensitivity reactions to either purified enzyme or crude schistosomal extracts. It is suggested that an in vivo correlation between worm burden and manifestations of the allergic response may be perturbed by high titres of non-specific IgE or other homocytotropic antibodies, thus accounting for false negative skin test reactions. Alternatively, a return to low or subnormal IgE levels may allow the restoration of the allergic response, giving rise to false positive reactions. Purified schistosomal antigens offer certain advantages over crude skin test preparations in terms of uniformity of antigen content, dosage and specificity. In addition, the enzyme may represent a species-specific tool for new immunochemical analyses of schistosomiasis.

Animals↗
PubMed1978

An analysis of the role of IgE in intolerance to aspirin and tartrazine.

Total serum IgE and eosinophil count were determined for 30 patients with intolerance to aspirin. Total IgE levels in the aspirin intolerant patients were similar to those expected in a non-atopic population. In contrast, total eosinophil count (TEC) tended to be elevated in the aspirin intolerant group. Elevated TEC was observed both in bronchospastic (57%) and in urticarial (25%) aspirin intolerance. Specific anti-aspiryl and anti-tartrazyl antibodies of the IgE class were assayed by the galactosidase immunosorbent test (GIST). IgE anti-aspiryl antibodies were possibly detected in one patient, but did not correlate with clinical intolerance to aspirin. It is unlikely that the clinical symptoms and the eosinophilia of intolerance to aspirin and tartrazine are mediated by antibodies of the IgE class.

Aspirin↗
PubMed1977

Dielectric dispersion of actin.

The dielectric dispersion of G-actin was 7 X 10(6) Hz, and the low frequency reduced dielectric increment 0.99 +/- 0.15 ml/mg. The dielectric increment of F-actin in the range 10(5) to 10(8) Hz was very low, about 0.3.

Actins↗
PubMed1976

A metallurgical examination of fractured stainless-steel ASIF tibial plates.

Between 1970 and 1973 99 tibial fractures were treated by rigid internal fixation with ASIF plates. The fractures were all regarded as sufficiently stable for exercise without weight bearing, thus needing no additional external support during the healing period. Four of the plates broke late in the healing period, after the onset of weight bearing. These fractures had some degree of delayed union with slight resorption of the bone ends, resulting in cyclical bending of the plate. Examination of 2 of the fractured plates by scanning electron microscopy, electron microprobe analysis and optical metallography revealed that the primary cause of plate fracture was fatigue. There was no evidence that corrosion fatigue or inclusion content were factors leading to plate fracture.

Adult↗
PubMed1976

A galactosidase immunosorbent test for human immunoglobulin E.

We report here the development of a galactosidase-immunosorbent test (GIST) for immunoglobulin E (IgE) antibodies in which the amount of galactosidase adsorbed to a cellulose disc is a single valued function of IgE concentration in human serum. Rabbit anti-IgE immunoglobulin insolubilized on cellulose discs is incubated sequentially with human serum, sheep anti-IgE serum, and a covalent conjugate of rabbit antisheep immunoglobulin with the enzyme beta-D-galactoside galactohydrolase (E.C.) 3.2.1.23). Colorimetric assay of enzyme conjugate adsorbed to discs permits quantitation of 1.0 to 25 ng of IgE per test. Concentrations of IgE in 48 sera as measured by the GIST gave a linear correlation coefficient of 0.97 with IgE concentrations as determined by radioimmunoassay. Preliminary studies indicate that the GIST makes possible nonisotopic measurement of ragweed-specific IgE antibiotics in human serum. The GIST for IgE is simple to perform and requires neither short-lived radioisotopes, expensive scintillation detection equipment, nor scarce, purified IgE.

Allergens↗
PubMed1976

Synthesis and secretion of light-chain immunoglobulin in two successive cycles of synchronized plasmacytoma cells.

Suspension-cultured mouse plasmacytoma cells (MPC-11) were accumulated in the late G1 phase by exposure to isoleucine-deficient medium for 20-24 h. The arrested culture was fed with complete medium enabling the cells to continue the cell cycle synchronously, undergo mitosis, and enter a second cycle of growth. This method of synchronization left the protein-synthesizing ability intact as judged by the polysome profile and the capacity of the cells to incorporate labeled amino acids into protein after the restoration of isoleucine. After incubation in isoleucine-deficient medium and the addition of isoleucine to the culture, cells entered the S phase after a short lag, as judged by [3H]thymidine incorporation into nucleic acid and by spectrophotometric measurement of nuclear DNA. The cells were in mitosis between 12 and 18 h as judged by the increase in cell count and analysis of cell populations on albumin gradients. Synthesis and secretion of light-chain immunoglobulin were maximal in the late G1/early S phase of the first cycle. During late S phase, G2 phase, and mitosis, both synthesis and secretion were observed to be at a low level; however, immediately after motosis the cells which then entered the G1 phase apparently commenced synthesis of light chain immunoglobulin straight away, although secretion of labeled material remained at a low level.

Cell Count↗
PubMed1976

A galactosidase immunosorbent test for carcinoembryonic antigen.

A galactosidase immunosorbent test for carcinoembryonic antigen (CEA) is described in which the amount of galactosidase adsorbed to a cellulose disc is a hyperbolic function of CEA concentration. Thus, molecules with CEA-like activity can be characterized by mathematical analysis of data obtained from the galactosidase immunosorbent test. By such analysis, CEA-reactive molecules in normal human plasma were distinguished from normal cross-reacting antigen and from authentic CEA. Variation of the amount of antibody-enzyme conjugate used in the galactosidase immunosorbent test permitted CEA-reactive material in plasma of a patient with rectal carcinoma to be antigenically distinguished from the CEA-reactive material in urine of a patient with bladder carcinoma. The galactosidase immunosorbent test is a useful tool for analysis of CEA-reactive molecules.

Absorption↗