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Biomedical subjects

H Friedman

Publications and source records attributed to H Friedman.

At least 631 records · Page 35Linked to original sources

Immunological tolerance to microbial antigens I. Absence of specific antibody-containing cells in lymphoid tissue of mice injected at birth with Shigella soluble antigen.

Friedman, Herman (Albert Einstein Medical Center, Philadelphia, Pa.). Immunological tolerance to microbial antigens. I. Absence of specific antibody-containing cells in lymphoid tissue of mice injected at birth with Shigella soluble antigen. J. Bacteriol. 92:390-397. 1966.-Injection of a relatively large concentration of Shigella soluble antigen (SSA) into newborn mice results in specific immunological tolerance (paralysis) characterized by inability of the animals to form normal levels of anti-Shigella agglutinins upon subsequent challenge immunization with Shigella. Spleen and lymph nodes from Shigella-tolerant mice, as well as from normal and control immunized mice, were examined by the indirect immunofluorescence technique for evidence of cells containing anti-Shigella antibody. It was found that mice sacrificed at periodic intervals after neonatal administration of the tolerance-inducing inoculum of antigen and prior to and following challenge injection with a potential immunizing dose of SSA had only occasional specific fluorescing cells in spleens and lymph nodes. Tolerant mice also failed to develop significant levels of specific serum agglutinins after SSA challenge injection. In contrast, normal adult mice had a rapid appearance of numerous specific fluorescing cells in their spleens and lymph nodes, as well as a marked agglutinin response, after SSA immunization. Shigella-tolerant and normal control mice responded equally well with anti-Salmonella agglutinin formation and specific antibody-containing lymphoid cells after immunization with Salmonella antigen.

Journal Article↗

Immunological tolerance to microbial antigens. II. Suppressed antibody plaque formation to Shigella antigen by spleen cells from tolerant mice.

Friedman, Herman (Albert Einstein Medical Center, Philadelphia, Pa.). Immunological tolerance to microbial antigens. II. Suppressed antibody plaque formation to Shigella antigen by spleen cells from tolerant mice. J. Bacteriol. 92:820-827. 1966.-An indirect, localized, antibody plaque procedure has been used to demonstrate a marked difference in the number of antibody plaques formed with spleen cell suspensions from normal and Shigella-tolerant mice. Whereas challenge with soluble Shigella antigen (SSA) into normal mice, ranging in age from 4 to 40 weeks, resulted in a rapid rise in antibody plaque formation to Shigella-treated sheep erythrocytes, there was only a slight increase in plaque formation with spleen cell suspensions from similarly challenged mice which had been made tolerant to Shigella antigen during neonatal life. Apparently, the suppression of plaque formation to Shigella in tolerant animals was specific, since both Shigella-tolerant and normal mice responded equally well to untreated sheep red blood cells after challenge with sheep erythrocytes only. Spleen cells from nonchallenged Shigella-tolerant mice did not form significant numbers of antibody plaques to SSA-treated red blood cells during an observation period of 4 to 30 weeks after neonatal administration of antigen. "Nonspecific" increases in plaque formation to untreated sheep red cells occurred with spleen cell suspensions from both normal and SSA-tolerant mice after challenge injection with Shigella antigen, with or without sheep erythrocytes. Such a response suggested an adjuvant effect for the endotoxin-containing Shigella antigen even in mice tolerant to the agglutinogenic moiety of SSA. The results of these experiments support the view that specific antibody-forming cells are either absent or in low number in lymphoid tissue from mice specifically tolerant to Shigella antigens. It seems unlikely that the low postchallenge agglutinin titers of tolerant mice are due to suppressed antibody formation by normal numbers of individual antibody-producing cells, or due to "masking" of normal antibody production by persisting circulating antigen.

Animals↗

Depletion of liver and esophageal epithelium vitamin A after chronic moderate ethanol consumption in rats: inverse relation to zinc nutriture.

This study was designed to determine whether chronic moderate ethanol ingestion alters the levels of vitamin A of liver and esophageal epithelium and if this is dependent on zinc nutriture. Forty male Sprague-Dawley 4-week-old rats were divided into five groups: zinc-deficient (0.9 ppm), ethanol-fed; zinc-deficient; zinc-adequate (25 ppm); zinc-adequate (25 ppm), ethanol-fed; and zinc-supplemented (50 ppm), ethanol-fed. All rats received liquid Lieber-DeCarli diet containing 4,000 IU per liter of vitamin A for 5 weeks. Zinc-deficient, ethanol-fed rats and zinc-adequate, ethanol-fed rats and zinc-supplemented, ethanol-fed rats received 15.5% of the caloric intake as ethanol while zinc-deficient and zinc-adequate rats received isocaloric amounts of maltose dextrin. All groups were pair-fed to zinc-deficient, ethanol-fed rats. In addition, a group of eight rats designated as weight-restricted controls were fed a diet similar to the one given to zinc-adequate rats but in the amount to obtain a final weight as in the zinc-deficient group. After 35 days, the liver histology was normal in all rats, and no fat accumulation was noted. Hepatic vitamin A concentration was significantly decreased in zinc-adequate, ethanol-fed rats (41 +/- 10 micrograms per gm) and further in zinc-supplemented, ethanol-fed rats (12 +/- 5 micrograms per gm) as compared to controls (137 +/- 49). A highly significant negative correlation between serum zinc and liver vitamin A was found in ethanol-fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tissue distribution of diazepam and its metabolite desmethyldiazepam: a human autopsy study.

Concentrations of diazepam (DZ) and desmethyldiazepam (DMDZ) were determined quantitatively in the brain, skeletal muscle, heart, liver, lung, fat, adrenal gland, and kidney in 14 autopsied patients who had been treated with DZ or clorazepate (a DMDZ prodrug) during their hospital course. To facilitate interpatient comparisons, all tissue concentrations from the same patient were normalized as ratios to the concentration of DZ or DMDZ found in that patient's skeletal muscle. Tissue uptake ratios were not influenced by gender or chronicity of dosage. Distribution equilibrium was reached in at least two hours. Tissue uptake ratios differed considerably among tissues for DZ and DMDZ. Mean (+/- SE) DZ uptake ratio was highest for adrenal gland (12.1 +/- 5.9), liver (5.9 +/- 1.9), heart (4.3 +/- 1.0), and kidney (4.0 +/- 1.0), with lower values for lung (2.1 +/- 0.5), fat (2.2 +/- 0.4), and brain (1.9 +/- 0.4). Similar patterns were observed for DMDZ, except for significantly lower fat uptake. Extrapolating to an average body composition for a 70 kg man with 16% body fat, the largest fractions of total body stores of DZ would be found in muscle (42%), fat (35%), and liver (12%), with smaller stores in brain (4.3%), lung (3.3%), heart (1.7%), kidney (2.0%), and adrenal gland (0.24%).

Absorption↗

Induction of an atypical interferon by bacteroides fragilis and Escherichia coli in experimental infections and in leukocyte cultures.

Previous reports have shown that Bacteroides fragilis may enhance the pathogenicity of coinfecting enterobacteriaceae by interfering with the host's immune response. With the present study, we have investigated the possible role of interferons (IFN) in mediating these effects. Mice injected with B. fragilis developed moderate serum levels of IFN that appeared just prior to alterations of the animals' immunity described earlier. The IFN was neutralized by treatment with anti-IFN-alpha/beta-antibodies or hydrochloric acid; hence it displayed the same "atypical" characteristics as IFN found in patients with immuno-compromising diseases such as AIDS, systemic lupus erythematosus or rheumatoid arthritis. Escherichia coli displayed the same induction patterns as B. fragilis, while gram-positive bacteria induced "regular" IFN alpha/beta and gamma. Spleen cells, peritoneal macrophages, or liver leukocytes taken from B. fragilis or E. coli-injected animals 6 h post infection were refractory to IFN induction by E. coli lipopolysaccharide in vitro; cells from mice infected with gram-positive organisms showed normal or enhanced responsiveness.

Animals↗

Effects of LSD-25 on performance of a visual discrimination task in brain-damaged rats.

Rats subjected to either a frontal cortex lesion or to a sham operation were trained to discriminate between a lighted and unlit alley in order to escape shock. Following intubation with either placebo or LSD-25 (1.0 MG/KG), they were given discrimination trials 24 hr, 1 week, 2 weeks, 3 weeks, 4 weeks, and 5 weeks later. During the last 3 sets of trials, the discrimination task was increased in difficulty each week. A relatively long-term single-dose drug effect was observed in decreased accuracy of performance, with a drug-lesion interaction reflected in slower running time upon initial increase in level of task difficulty.

Animals↗

Depression before and after uterine cervix and breast cancer neoadjuvant chemotherapy.

Depression in cancer patients is common and may affect treatment outcome either directly (by lowering defenses) or indirectly (by lowering compliance). Neoadjuvant chemotherapy for advanced uterine cervix or breast cancer is a strenuous undertaking and may lead to depression and impair patients' willingness to comply with the rest of the treatment (eg, surgery or radiotherapy). We compare Beck Depression Inventory (BDI) scores both before and after neoadjuvant chemotherapy in order to verify if depression influences treatment outcome. We studied 22 advanced uterine cervix and 20 breast cancer patients submitted to three courses of neoadjuvant chemotherapy. We used cisplatin and ifosfamide for cervix, and fluorouracil, adriamycin, and cyclophosphamide for breast cancer. We did not identify significant differences in the number of depressed patients, before and after treatment. Cognitive affective, somatic-performance, and total BDI scores were not significantly different from before to after chemotherapy for both breast and uterine cervix cancer. After treatment, the number of depressive breast cancer patients increased while the number of uterine cervix cancer patients decreased. This trend to depression was found more often in less responsive breast cancer patients than in the more responsive cervix cancer patients. We were not able to link depression to treatment failure or success, but patients who responded to treatment were less depressed at the end of treatment.

Adult↗

The effect of seprafilm and interceed on capsule formation around silicone discs in a rat model.

The insertion of a foreign substance, such as a breast implant into mammalian soft tissues, evokes a wound healing response that culminates in a dense connective-tissue envelope or capsule surrounding the implant. Several biodegradable products, such as Seprafilm (carboxymethylcellulose and hyaluronic acid) and Interceed (oxidized regenerated cellulose), have been demonstrated to inhibit adhesions in abdominal and gynecologic surgery. The ability of these cellulose compounds to inhibit capsule formation was addressed in this investigation. Twenty-eight rats were implanted intermuscularly with either plain silicone discs (10 animals), discs wrapped in Seprafilm (10 animals), or discs covered with Interceed (8 animals). Additional control animals (6 animals) consisted of two that had sham operations, two animals implanted with Seprafilm only, and two more implanted with Interceed only. Animals were sacrificed in pairs at varying time intervals after implantation (2, 4, 8, 12, and 16 wk), and the tissues around the silicone discs were analyzed with light microscopy. Control animals were sacrificed at 8 wk. Both Interceed and Seprafilm slowed the formation of a capsule around the implanted silicone discs as both products were degraded. Evidence of residual material, presumably Seprafilm and Interceed, was seen intracellularly in animals 3 to 4 mo, respectively, after implantation. However, neither material prevented the eventual formation of a fibrous capsule around the silicone discs. The results of this study suggest that encapsulating foreign substances with these types of biodegradable materials will not significantly hinder capsule formation. A more direct attack on the wound healing mechanism may provide a definitive solution for capsule problems with implanted materials.

Animals↗