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Biomedical subjects

C O Jacob

Publications and source records attributed to C O Jacob.

63 records · Page 4Linked to original sources

Synthetic vaccines.

Explore the source record for details and available documents.

Adjuvants, Immunologic↗

Antibodies against synthetic peptides of the B subunit of cholera toxin: crossreaction and neutralization of the toxin.

Six peptides corresponding to various segments of the B subunit of cholera toxin have been synthesized and covalently linked to tetanus toxoid. Of the antibodies raised in rabbits against these conjugates, four crossreacted to different extents with the intact B subunit and whole native cholera toxin. Antisera to the peptide of sequence 75-85 were not crossreactive, whereas elongation by six amino acid residues resulted in a peptide (69-85) leading to antibodies crossreactive with the cholera toxin. Of most interest was peptide CTP3 (50-64), which was the only one that reacted with antisera to cholera toxin and which led to antibodies reacting with the cholera toxin to a similar level as its homologous peptide-antipeptide reaction. Indeed, antisera to CTP3 neutralized significantly the biological activity of cholera toxin, as followed by skin vascular permeability and by fluid accumulation in ligated small intestinal loops of rabbits.

Amino Acid Sequence↗

Prolonged opacification of the gallbladder after oral cholecystography: a reevaluation of its clinical significance.

The frequency of prolonged opacification of the gallbladder after oral cholecystography was determined in several conditions that are manifestly or reputedly associated with gallbladder dysfunction: in patients with gallstones, in cases of "biliary colic" with normal cholecystograms, in postvagotomy patients, and in diabetics. These groups were compared with asymptomatic controls and to patients with irritable bowel syndrome. A dietary fat intake of at least 50 g between the first and last films taken was ensured in all subjects. The effect of fat deprivation was separately studied in asymptomatic controls. Prolonged opacification was encountered in approximately two-thirds of patients with gallstones, in two-thirds of patients with "acalculous biliary colic," in two-thirds of healthy subjects deprived of fat, and in about one-third of postvagotomy patients and diabetics. It was not seen in a single patient with irritable bowel syndrome, and it was encountered in only 1 out of 17 controls whose diet included a fat supplement. These differences were highly significant (p less than 0.0001).

Adult↗

Increased risk of lung cancer in patients with chondromatous hamartoma.

Fifty-two patients with chondromatous hamartoma of the lung (CHL) operated upon in one medical center in Israel during the years 1960 to 1975 were followed through the end of 1976 for occurrence of malignancy. In 51 patients, the operation followed the finding of a coin lesion in a routine chest x-ray film (32 cases) or an x-ray film taken due to symptoms related to the chest (19 cases). In one case, it followed a cytologic diagnosis of bronchogenic carcinoma. Four cases of carcinoma of the lung were observed in this group, three of them 2 to 10 years after the CHL was first observed; in the fourth the CHL was found during an operation for lung cancer. All four lung cancers were located in the same lobe as and in proximity to the CHL. Since hamartomas were randomly distributed among the lobes, this spatial association is highly significant (p = 0.0016). The risk of lung cancer in CHL patients was estimated to be 6.3 times higher than the age-sex-ethnic adjusted rate expected for the general Israeli population. No increased risk for malignancies of other sites was found.

Adult↗

Vesnarinone is a selective inhibitor of macrophage TNF(alpha) release.

Vesnarinone is an experimental drug that has been used successfully in the treatment of congestive heart failure patients. In this report we investigate the effect of vesnarinone on the cytokine secretory products of mononuclear phagocytes. In a concentration-dependent manner, the drug inhibits the endotoxin(LPS)-stimulated release of tumor necrosis factor (TNF) alpha and suppresses interleukin(IL)-6 release, but does not affect the release of IL-1 alpha, IL-10 and leukemia inhibitory factor (LIF) by mouse peritoneal macrophages. Using competitive polymerase chain reaction (PCR) analyses, we find that vesnarinone significantly reduces TNF(alpha), but not IL-10 mRNA. In addition to LPS, the drug inhibits TNF(alpha) release induced by several other stimuli. The inhibitory effect of the drug on the TNF(alpha) biosynthesis can be observed in differentiated human monocytes, in macrophage cell lines, and in synovial adherent cells from rheumatoid arthritis patients. Although the precise mode of action of vesnarinone in the signal transduction pathway leading to the selective inhibition of TNF(alpha) is not known, the drug might be useful in the treatment of diseases involving that cytokine.

Adjuvants, Immunologic↗

Epitopes of the cholera family of enterotoxins.

Hybridoma-derived monoclonal antibodies were raised to enterotoxins of the cholera family and to chimeric B-subunit proteins in which individual amino acid residues of a heat-labile, cholera-related enterotoxin from an Escherichia coli strain of porcine origin (P-LT) were substituted with corresponding residues from such an enterotoxin from an E. coli strain of human origin (H-LT). Single amino acid substitutions were found to have profound effects on the physicochemical behavior of the proteins and on their immunologic reactivity. With the use of enzyme-linked immunosorption assays (ELISAs) with and without the GM1 ganglioside receptor for these toxins, several distinct epitopes in GM1-binding domains were identified by different monoclonal antibodies. Polyclonal rabbit antisera to synthetic peptides of the cholera enterotoxin B subunit were cross-reactive to various degrees with the proteins in our library, which include two different cholera enterotoxins, two H-LTs, P-LT, and four chimeric proteins. Some of these reactions were blocked by GM1 ganglioside but not by the oligosaccharide of GM1, a finding suggesting that the peptides generated antibodies to epitopes near, but not in, a GM1-binding domain. A hypothetical evolutionary tree based on the reported amino acid sequences of the various enterotoxins is constructed. As additional enterotoxins are described, it will be interesting to determine if and where they fit in this scheme.

Amino Acid Sequence↗

Antigenic determinants of the cholera/coli family of enterotoxins.

Hybridoma-derived monoclonal antibodies were raised to enterotoxins of the cholera family and to chimeric B-subunit proteins in which individual amino acid residues of a heat-labile, cholera-related enterotoxin from an Escherichia coli strain of porcine origin (P-LT) were substituted with corresponding residues from such an enterotoxin from an E. coli strain of human origin (H-LT). Single amino acid substitutions were found to have profound effects on the physicochemical behavior of the proteins and on their immunologic reactivity. With the use of enzyme-linked immunosorption assays (ELISAs) with and without the GM1 ganglioside receptor for these toxins, several distinct epitopes in GM1-binding domains were identified by different monoclonal antibodies. Polyclonal rabbit antisera to synthetic peptides of the cholera enterotoxin B subunit were cross-reactive to various degrees with the proteins in our library, which include two different cholera enterotoxins, two H-LTs, P-LT, and four chimeric proteins. Some of these reactions were blocked by GM1 ganglioside but not the oligosaccharide of GM1, a finding suggesting that the peptides generated antibodies to epitopes near, but not in, a GM1-binding domain. A hypothetical evolutionary tree based on the reported amino acid sequences of the various enterotoxins is constructed. As additional enterotoxins are described, it will be interesting to determine if and where they fit in this scheme.

Amino Acid Sequence↗

Genetic variability in tumor necrosis factor production: relevance to predisposition to autoimmune disease.

Rather than being involved merely in the effector arm of inflammatory processes that contribute to autoimmune organ destruction, a primary involvement of TNF may be in some of the more basic mechanisms that occur in autoimmune disease. In this review, data are presented on TNF-alpha that suggest the involvement of this cytokine in the genetic predisposition to autoimmune diseases such as lupus nephritis.

Animals↗