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Biomedical subjects

A Saltzman

Publications and source records attributed to A Saltzman.

71 records · Page 4Linked to original sources

Postinflammatory increase of lymphatic absorption from the peritoneal cavity: role of diaphragmatic stomata.

During the healing phase of a chemical peritonitis in rats, absorption of various inocula from the peritoneal cavity into the draining lymph nodes is increased. Heretofore, this phenomenon has been attributed to fibrosis and shrinkage of the greater omentum. The loss of the sequestering function of the omentum allows the inoculum more ready access to the lymphatic vessels in the diaphragm where it is absorbed. In the present work, it is demonstrated that the chemical peritonitis also widens the stomata in the roofs of the diaphragmatic lymphatic lacunes. Both increased access and larger openings contribute to enhanced lymphatic absorption in the postinflammatory state.

Absorption↗

A method for evaluating regional effects of cytotoxic drugs on proliferating cells in lymph nodes.

Tin powder, injected into both hindfeet of rats, caused intense proliferation of the plasma cell series in the draining lymph nodes. The hyperplasia was evaluated by weight and by histology of the nodes. This simple, rapidly executed model was used to evaluate the delivery of locally injected cytotoxic drugs to regional lymph nodes. Inhibition of hyperplasia was compared to both internal controls (contralateral node) and external controls. Mitoxantrone and methotrexate, injected locally according to certain doses and schedules, were effective in reducing the lymph node hyperplasia with little or no systemic effects. This model should assist in the evaluation of drugs, schedules, and adjuvants that might be used in the regional treatment of lymph node hyperplasia or metastic neoplasia.

Animals↗

Nonspecific stress prevents relapses of experimental allergic encephalomyelitis in rats.

Rats with experimental allergic encephalomyelitis (EAE) develop paralysis, from which most of them recover. It has been hypothesized that spontaneous remission in EAE is due to the stress of paralysis and the subsequent hypersecretion of endogenous immunosuppressive adrenal glucocorticoids. Spontaneous relapse after a remission is thought to occur when the stress of paralysis and the adrenal response to it are terminated. In the present work, this theory has been tested in a newly developed relapsing form of EAE in rats. After an initial attack characterized by paralysis, the control rats had a remission and then a second episode of paralysis (relapse). In contrast, rats subjected to restraint during the remission period were protected from relapses. Injections of adrenal glucocorticoids during the remission had a similar protective effect. These findings support the hypothesis that remissions and relapses in EAE are caused by the occurrence and subsequent disappearance of the adrenals' immunosuppressive response to the stress of paralysis, because the addition of stress during the period of remission maintained the adrenals' hyperactive state and thereby prevented relapses.

Adrenal Glands↗

Percutaneous inoculation of lymph nodes.

Injections into rat lymph nodes are easily performed percutaneously, without the need for a skin incision, if the nodes are enlarged in advance. The requisite enlargement of the popliteal lymph node can be obtained in 2 or 3 weeks by a single injection of tin powder or other particulate material into the foot. This method may be especially useful when multiple intranodal inoculations are contemplated.

Animals↗

Regional suppression, therapy after onset and prevention of relapses in experimental allergic encephalomyelitis by mitoxantrone.

Mitoxantrone, a new antineoplastic anthracenedione drug, suppressed the development of experimental allergic encephalomyelitis (EAE) in rats when administered during the incubation period. One dose of mitoxantrone had a favorable effect on EAE even when withheld until after the onset of clinical signs. In a model of relapsing EAE, a single dose during a remission prevented the expected relapse. Mitoxantrone had a particularly favorable effect when administered at the site of inoculation of the encephalitogenic antigen and adjuvant, indicating the importance of its interaction with the regional draining lymph nodes. These results support the possible clinical use of mitoxantrone for immunosuppression.

Animals↗

Adoptive transfer of allergic encephalomyelitis by inoculation of cells into lymph nodes.

Experimental allergic encephalomyelitis can be transferred passively by lymph node cells from actively immunized donor rats to immunologically naive syngeneic recipients. In the present work, passive transfer was accomplished by direct inoculation of donor cells into the recipient's lymph node, and this route was more effective than the conventional intravenous or intraperitoneal routes.

Animals↗

Clofazimine enteropathy: possible relation to Peyer's patches.

Clofazimine administered orally to rats and mice caused pigmentation of the intestines, draining lymph nodes, fat, and other tissues and organs. Peyer's patches were always more deeply colored than the remainder of the intestine. A microscopic study revealed crystal-containing epithelioid cell granulomas in the patches and in the draining mesenteric lymph nodes but not in the remainder of the gut. During the evolution of the granulomas, some of the epithelioid cells were capable of phagocytosing an iron complex, a circumstance which made it possible to get detailed views of the clofazimine crystals in paraffin sections by negative contrast in histochemical stains for iron. The granulomas appeared after three oral treatments during 1 week, but were better developed after six or more treatments during 2 or more weeks. Similar observations were made in three strains of rats and in mice. We hypothesize that the greater pigmentation of Peyer's patches and their granulomatous response to clofazimine might indicate a special susceptibility to toxic effects of the drug. Whether or not this susceptibility is the starting point for an enteropathy can only be determined by examination of affected human tissues and by further animal experimentation.

Animals↗

Immunochemical characterization of the androgen-dependent spermine-binding protein of the rat ventral prostate.

A solid-phase radioimmunoassay was developed to measure the level of the androgen-dependent spermine-binding protein (SBP) in the cytosol fraction of the rat ventral prostate during endocrine manipulation. The concentration of SBP and immunologically cross-reacting material (CRM) in the ventral prostate was at least 5000 times higher than the level of CRM detected in rat serum or cytosol from other rat tissues. Cytosol from the ventral prostate of intact rats was separated by DEAE-cellulose chromatography into three major fractions of CRM. One of these fractions corresponded to the elution position of SBP. Cytosol prepared from rats 48 h after castration lacked SBP and one of the two other fractions of CRM. This loss coincided with an increase in CRM in the remaining fraction. No significant difference was detected in the total level of CRM when intact and 48 h-castrated rats were compared. Injection of rats with 5 alpha-dihydrotestosterone (DHT) immediately after castration prevented these changes in the profile of CRM. Several proteins cross-reacting with antibodies to purified SBP were detected in cytosol by using an immunoblot procedure. The highest-Mr band corresponded to SBP. The effect of short- and long-term castration and subsequent DHT treatment on CRM was studied by using the immunoblot technique. Short-term castration (2 days) led to the disappearance of CRM coinciding with SBP (Mr 35 000-38 000) and an increase in smaller forms of CRM (Mr 24 000 and 22 000). Injection of rats with DHT 2 days after castration led to the reappearance of CRM corresponding to SBP, which returned to normal levels within 4 to 5 days of treatment. Long-term castration (up to 14 days) led to a gradual disappearance of all CRM; subsequent DHT treatment led to the reappearance of all forms of CRM and normal levels were attained within 5 days. We have identified SBP and the various forms of CRM as a secretory product of the rat ventral prostate by immunohistochemical staining and by DEAE-cellulose fractionation of prostatic fluid. Prostatic fluid is rich in proteolytic activity and these proteinases may be responsible for processing SBP to small forms of CRM.

Animals↗

Repeated toxic injury of peritoneum: accumulation of toxicity and adaptation to injury.

In order to develop new methods for the study of pathogenesis of post-injury fibroplasia, a rat model of chemical peritonitis was explored. Sodium hypochlorite (NaOCl) of various concentrations was injected intraperitoneally one or more times using different intervals between doses. Some time later, the surface fibrosis of liver, spleen, omentum and other abdominal organs was evaluated. A dose-response relation at intermediate concentrations and an apparent threshold at low concentrations were observed. Fibroplasia was increased by repeated doses (accumulation) but it was ameliorated compared to the same total amount of chemical given as a single injection (adaptation during repeated dosing). The rapid disappearance of the chemical irritant and the large size and easy accessibility of the peritoneal cavity suggest that this model may be useful in further study of chemical toxicity and fibroplasia in relation to human fibrosing diseases and injuries (trauma, surgery, peritoneal dialysis). The model has the unique feature of evaluating the morphological effects of the toxic injury and secondary functional effects at the same time.

Adaptation, Physiological↗

Peritoneal toxicity of water: a model of chronic peritonitis caused by osmotic dysequilibrium in rats.

The purpose of this work was to determine whether the osmotic dysequilibrium created by intraperitoneal (i.p.) injection of pure water has any permanent, damaging toxic sequelae. Rats were injected i.p. with pure water on five successive days. Necropsies were performed 1 week after the last injection. Necropsies revealed fibrosis of peritoneal surfaces of liver and spleen, similar to the effects of chemical irritants but milder. The severity of the lesions depended on the dose of water and the number of injections. A few minutes of contact with pure water was sufficient to ensure subsequent development of fibrosis. Soon after the initial injury, the inoculum became less hypotonic and then isotonic. Isotonic or moderately hypotonic electrolyte solutions did not produce peritoneal fibrosis but very hypotonic solutions were toxic. Injection of the synthetic compound 48/80, which is known to cause discharge of mast cell granules, did not produce peritonitis, nor was contamination by endotoxin or by blood responsible for the lesions. Injection of water may be a useful method for investigating the role, if any, of mast cells and/or mesothelial cells in the toxic effects of osmotic dysequilibrium.

Animals↗

Inhibition of experimental allergic encephalomyelitis by lithium chloride: specific effect or nonspecific stress?

Intraperitoneal injections of lithium chloride inhibited development of experimental allergic encephalomyelitis (EAE) in rats. The degree of inhibition was inversely related to the intensity of the immunologic stimulation, which depended on the choice of adjuvant. High dosage of lithium, the intraperitoneal route, and an intermittent schedule of administration were required to achieve suppression of EAE. This suggested that the immunosuppression was a toxic effect, mediated, at least in part, through the hypothalamic-pituitary-adrenal cortex axis. This hypothesis was supported by evidence that the lithium treatment schedule, especially the intermittent schedule, had caused adrenal cortical activation with thymolysis in intact rats and that it was lethal to adrenalectomized rats. Lithium also inhibited EAE produced by adoptive immunization, thus implicating the efferent arm of the immune response. A single dose of lithium was effective in this form of EAE, even in adrenalectomized rats. Therefore lithium affects EAE by both specific immunosuppressive and nonspecific adrenocortical-dependent mechanisms.

Adrenal Glands↗

Ascites produced in rats without tubercle bacilli or tumor cells.

Intraperitoneal injection of rats with two doses of pertussis vaccine produces a small amount of ascitic fluid. Much larger amounts of fluid are produced when two spaced injections of the vaccine are preceded by a small amount of liquid petrolatum. A similar result is obtained by a single injection of pertussis vaccine emulsified in liquid petrolatum and Arlacel A. Ascites produced without tubercle bacilli or tumor cells may increase the use of rats for antibody production.

Adjuvants, Immunologic↗

Abdominal cocoon: an animal model for a complication of peritoneal dialysis.

OBJECTIVE: The purpose of this work was to develop an animal model of sclerosing encapsulating peritonitis, a complication of continuous ambulatory peritoneal dialysis in which the intestines are conglomerated into an ovoid cocoonlike structure. DESIGN: Toward this end, rats were injected with a chemical irritant (household bleach) intraperitoneally. One week later, before the resultant peritonitis could cause adhesions, 10 or 25 mL of fresh whole rat blood was injected into the peritoneal cavity. Two weeks later, the effect of the treatments was evaluated by macroscopic and microscopic study. RESULTS: The irritant caused a chemical peritonitis. The subsequently injected blood clotted on the surfaces of the inflamed intestines, and contraction of the clot (syneresis) was responsible for bringing the intestinal loops together. This conglomeration was made permanent by the fibrosis evoked by the chemical peritonitis. The end result was an ovoid encapsulated mass of intestines and other viscera. CONCLUSION: An animal model for an abdominal cocoon has been produced. It can be used for studies of the pathogenesis and prevention of this complication of peritoneal dialysis.

Animals↗