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Biomedical subjects

A J Bridges

Publications and source records attributed to A J Bridges.

68 records · Page 4Linked to original sources

Synthesis and biological activity of 5-amino- and 5-hydroxyquinolones, and the overwhelming influence of the remote N1-substituent in determining the structure-activity relationship.

A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group of common piperazinyl and 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against a variety of bacteria, and in vivo efficacy in the mouse infection model. The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and N1 (ethyl, cyclopropyl, difluorophenyl) was also studied. The results showed that several of the structure-activity conclusions regarding side-chain bulk at C7, the effect of halogen at C8, and the effect of the C5-amino group were greatly influenced by the choice of the N1-substituent. Several outstanding broad spectrum quinolones were identified in this work. In particular, the spectrum and potency of the 7-piperazinyl quinolones could be greatly enhanced by the judicious choice of C5-, C8-, and N1-substituents.

Alkylation↗

T helper-cell leukemia/lymphoma: presentation as an acute immune-mediated illness.

A 36-year-old man presented with an acute immune-mediated illness characterized by leukocytoclastic vasculitis and polyarthritis. Evaluation of the synovial fluid, bone marrow, and peripheral blood revealed large numbers of abnormal lymphoid cells labeling a 4B4-positive, CD4-positive, IL-2 receptor-negative, helper T cells. Hypergammaglobulinemia, immune complexes, high levels of serum IL-2 receptors, serum antibodies against foreign alloantigens, and specific cytolysis of the patient's leukemic cells by his normal CD8+ T lymphocytes suggest an interaction of the malignant cells and his normal immune cells. Thus, some of the rheumatologic symptoms leading to the diagnosis of leukemia appear to reflect an immunoregulatory imbalance manifested by B-cell hyperactivity, likely induced by the malignant helper T cells, and attempted regulation of his malignant T cells by normal lymphocytes.

Adult↗

Calmodulin content in human central nervous system tumors.

Benign and malignant brain tumors and normal cerebral cortex were assayed for calmodulin content by enzymatic and radioimmunoassay techniques. Normal cerebral cortex contained more (8.31 +/- 1.27 vs 3.30 +/- 0.42 micrograms/mg protein) calmodulin than the brain tumors. The contents of calmodulin in the malignant glioblastomas were significantly higher than the meningiomas (5.41 +/- 0.31 vs 2.97 +/- 0.16 micrograms/mg protein). These differences were independent of tumor location and persisted when calmodulin content was normalized for DNA rather than protein content. This data supports differences in the tissue calmodulin contents with normal cortex greater than primary malignant tumors greater than benign tumors greater than metastatic tumor tissue.

Brain Neoplasms↗

Lower extremity peripheral neuropathy and ischemic ulcers associated with giant cell arteritis.

A patient with previously treated, temporal artery biopsy proven, giant cell arteritis (GCA) developed lower extremity ulcers and sensory neuropathy. Sural nerve biopsy showed epineural vessels with focal mild chronic inflammation. The lower extremity skin and nerve abnormalities improved after retreatment with prednisone. The rare manifestations of lower extremity skin and peripheral nervous system involvement associated with GCA are discussed. GCA must be considered in lower extremity ischemic processes of the skin and peripheral nervous system.

Foot Diseases↗

Calmodulin content in human prolactin-secreting pituitary adenoma: an inverse relationship to serum prolactin levels.

Calmodulin content was evaluated in 3 prolactin-secreting pituitary adenomas (prolactinoma) and 3 normal anterior pituitary glands. The calmodulin content in the normal anterior pituitary tissue was quite consistent, 3.32 +/- 0.016 micrograms/mg protein. In contrast, calmodulin content varied almost 4-fold in the prolactinoma tissue (10.97, 8.50 and 3.00 micrograms/mg protein). Preoperative serum prolactin levels varied inversely with the prolactinoma calmodulin content (125, 257 and 3526 ng/ml, respectively). This study reveals that prolactinoma calmodulin content differs from normal, although it is not uniformly elevated as in other transformed tissues and that elevation of prolactinoma calmodulin content does not positively correlate with serum prolactin levels.

Adenoma↗

An examination of the utility of photogenerated reagents by using alpha-chymotrypsin.

As a test of the labelling characteristics of photogenerated reagents, an aryl azide was photolysed in the aromatic-binding locus of a protein of known tertiary structure. The acyl-enzyme derived from the reaction of alpha-chymotrypsin with the p-nitrophenyl ester of p-azido[(14)C]cinnamate was isolated and photolysed. About 60% of the acyl group is covalently bound to the protein after photolysis and deacylation, and labelled enzyme is inactive. The covalently attached label is localized in the C chain of chymotrypsin, and there are firm indications that the major labelled tryptic fragment of the C chain is that which constitutes the aromatic-binding locus of the enzyme. The high degree of labelling of that portion of the protein molecule predicted on the basis of the known chemistry and structure of alpha-chymotrypsin, provides gratifying confirmation of the utility of the photo-labelling method.

Acylation↗