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Biomedical subjects

L Rubin

Publications and source records attributed to L Rubin.

At least 19 recordsLinked to original sources

Lymphadenopathy, oligoclonal T cell receptor rearrangement and systemic lupus erythematosus.

To investigate the cause of generalized lymphadenopathy in case of systemic lupus erythematosus (SLE), we performed a molecular genetic analysis of lymph node, peripheral blood mononuclear cell and bone marrow specimens with T cell receptor and immunoglobulin gene probes. Oligoclonal T cell receptor rearrangements were detected in the lymph node cells. The oligoclonal T cell expansion observed is the first such example reported in SLE, and may be indicative of an immune response to specific antigenic challenge. Alternatively, these changes may represent the earliest phases of a malignant process. Molecular genetic investigations in autoimmune disease such as SLE can provide opportunities to enhance our understanding of the underlying condition, or reveal unexpected abnormalities requiring further assessment.

Blotting, Southern

Topoisomerase II-mediated DNA cleavage activity and irreversibility of cleavable complex formation induced by DNA intercalator with alkylating capability.

A group of chrysophanol and emodin derivatives with DNA-intercalating capability and with or without alkylating potential have been synthesized and shown to have antitumor activity in vitro. The topoisomerase II (Topo II)-mediated DNA cleavage activities induced by representative compounds 3-(2-chloroethylamino) methyl-1,8-dihydroxy-9,10-anthraquinone (SK-31690), 3-bis [(2-chloroethyl)amino]methyl-1,8-dihydroxy-9,10-anthraquinone (SK-31662), and 3-(2-hydroxyethylamino)methy-1,8-dihydroxy-9,10-anthraquinon e (SK-31694), and their cytotoxicities, have been investigated. All three compounds inhibited the kinetoplast DNA decatenation catalyzed by DNA Topo II. These compounds inhibited leukemia cell growth and stimulated, in a dose-dependent manner from 0.5 to 60 microM, the formation of Topo II-DNA cleavable complexes, when 3'-32P-labeled DNA was used. The mapping of Topo II-mediated DNA cleavage sites using HindIII-digested 3'-32P-labeled DNA showed that, at 10 microM, these compounds induced protein-linked DNA breaks that correlated with cytotoxicity, with respect to their maximal efficacy or the reciprocal concentration for the half-maximal effect. The reversibility study showed that the amounts of protein-linked DNA cleavage induced by 4'-(9-acridinylamino)methanesulfon-m-anisidide and VP-16 as well as SK-31694, which lacks alkylating potential, were markedly decreased during 30-sec exposure to 65 degrees or 0.5 M NaCl. In contrast, protein-linked DNA cleavages induced by SK-31662, which has two alkylating functionalities, and by SK-31690, which has one alkylating functionality in its structure, cannot be reversed during the 15-min exposure to 65 degrees or 0.5 M NaCl. These data suggest that Topo II is a major cellular target for cytotoxicity of these compounds. Furthermore, DNA intercalators with alkylating potential interact with Topo II-DNA cleavable complexes in an irreversible manner, with enhanced toxicity.

Alkylating Agents

Foreign-body osteitis of the metacarpal bone.

Foreign-body granulomas in the hand can appear secondary to an unrecognized foreign material. In a six-year-old boy, an extensive sterile osteitis of the second metacarpal bone appeared adjacent to a wood splinter.

Child

Comparison of titanium-mesh and porous disc electrodes for epicardial defibrillation.

The object of this study was to compare the effectiveness of chronically implanted porous electrodes with that of smooth mesh titanium electrodes of the same diameter but smaller effective surface area. The criteria used in evaluating the electrodes were (1) acute, subacute, and chronic resistance and (2) acute, subacute, and chronic defibrillation thresholds. Electrode pairs 2.5 cm in diameter were implanted in each of 17 dogs (ten mesh and seven porous). One electrode of each pair was sutured to the right ventricle and one to the left ventricle near the cardiac apex. Defibrillation threshold energy and total resistance were measured at the time of implantation and again 6 and 12 weeks after implantation. The mean initial resistance of the titanium electrodes was 131.7 omega; the mean defibrillation values for the porous electrode implant were 96.9 omega and 7.5 joules, respectively. Three to 6 weeks after implantation, the values for the titanium mesh electrode were 88.9 omega and 12.0 joules, while those for the porous electrode were 59.9 omega and 8.0 joules. In the chronic state, the figures for the titanium mesh electrode were 78.1 omega and 13.0 joules, while those for the porous electrode were 64.3 omega and 8.3 joules. We conclude that defibrillation can be achieved successfully with small epicardial electrodes. The findings suggest that a porous electrode, with its larger effective surface area, has lower electrode/tissue interface resistance in the acute and chronic phases, and, therefore, provides lower defibrillation threshold energy.

Animals

Ingestion of Legionella micdadei inhibits human neutrophil function.

Legionella micdadei is a human pathogen which survives within leukocytes. To determine how this organism escapes intracellular destruction, we examined its effect on human neutrophil activity. Neutrophils were allowed to ingest L. micdadei prior to evaluation of functional activity. Compared with control cells which did not ingest organisms, cells ingesting L. micdadei showed significantly depressed production of superoxide anion (24.5 +/- 9.0 nmol/10(6) cells per 15 min versus 6.9 +/- 3.2 nmol/10(6) cells per 15 min, respectively; P = 0.002), chemotaxis (43.9 +/- 0.8 mm versus 0.9 +/- 1.3 mm of directed migration, respectively; P = 0.001) and bactericidal activity against Staphylococcus aureus (97.9% versus 37.6% of ingested organisms killed, respectively; P = 0.001). Similar degrees of inhibition could not be demonstrated when either Staphylococcus aureus or Escherichia coli was ingested by cells prior to evaluation. Inhibition of neutrophil function did not occur when phagocytosis of L. micdadei was prevented. However, inhibition occurred with heat-killed as well as with viable organisms. The inhibition of neutrophil function by ingested L. micdadei may help explain the bacterium's ability to survive intracellularly and may begin to explain the pathogenesis of this disease.

Chemotaxis, Leukocyte

A specific population of gonadotrophs purified from immature female rat pituitary.

When dispersed pituitary cells from 14-day-old female rats were sedimented in a bovine serum albumin gradient, a fraction was isolated which consisted of almost 90 percent of large cells that stained purple in the periodic acid-Schiff (PAS) reaction. Immunostaining indicated that over 85 percent of these PAS-purple cells were gonadotrophs containing both follicle stimulating and luteinizing hormone. Reproducible cell cultures could be obtained on poly-L-lysine coated dishes. As early as the second day in culture, the secretion of both follicle stimulating and luteinizing hormone was highly stimulated by luteinizing hormone-releasing hormone. The effect of FSH was as marked as that on LH. The data suggest that the isolated gonadotrophs are a specific functional subtype.

Age Factors

Injectable fluid silicone therapy. Human morbidity and mortality.

Four patients who had received silicone injections had the following complications: migration, hepatic disease manifested as granulomatous hepatitis (previously undescribed, to our knowledge), hypopigmentation, and death. Silicone should now be considered as a possible cause of hepatic granulomas in an appropriate host.

Adult