Effects of aging on cell cooperation and lymphocyte responsiveness to cytokines

Functional activities and cell cooperation of macrophages (Mphi), T cells, and B cells of young and old Lewis rats were compared. Splenic M phi from young and old rats provided accessory help for T cell mitogenesis and B cell mitogenesis, provided accessory help for generation of PFC, and produced IL 1 equally well as measured in costimulator assays. Splenic T cells of aged Lewis rats, however, were poorly responsive in mitogen assays and did not respond to supplemental IL 2 and antigen with blast transformation and with increased help for B cells to produce PFC. "Old" B cells did not respond in vitro to mitogens with help from M phi and T cells, nor did they respond to B cell helper factor with increased PFC. The data indicate that hyporesponsiveness of the immune system, especially of B cells, in aged rats is due in part to defective reactivity to interleukins and cytokine(s) and to defective cell-cell cooperation.     

Physiological effects of an allozyme polymorphism: Glutamate-pyruvate transaminase and response to hyperosmotic stress in the copepod Tigriopus californicus

In order to regulate cell volume during hyperosmotic stress, the intertidal copepod Tigriopus californicus, like other aquatic crustaceans, rapidly accumulates high levels of intracellular alanine, proline, and glycine. Glutamate-pyruvate transaminase (GPT; EC 2.6.1.2), which catalyzes the final step of alanine synthesis, is genetically polymorphic in T. californicus populations at Santa Cruz, California. Spectrophotometric studies of homogenates derived from a homozygous isofemale line of each of the two common GPT alleles indicated that the GPT^F allozyme has a significantly higher specific activity than the GPT^S allozyme. Under conditions of hyperosmotic stress, individual adult copepods of GPT^F and GPT^F/S genotypes accumulated alanine, but not glycine or proline, more rapidly than GPT^S homozygotes. When young larvae were subjected to the same hyperosmotic conditions, GPT^S larvae suffered a significantly higher mortality than GPT^F or GPT^F/S larvae. These results suggest that the biochemical differences among GPT allozymes result in specific physiological variation among GPT genotypes and that this physiological variation is manifested in differential genotypic survivorships under some naturally occurring environmental conditions.This work was supported in part by a grant from the Lerner Fund for Marine Research of the American Museum of Natural History, an NIH Training Grant in Integrative Biology, and NIH Grants GM 28016 and GM 10452.     

Alpha 2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages

Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human alpha 2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both alpha 2-macroglobulin-trypsin and alpha 2-macroglobulin-methylamine inhibited macrophage production of superoxide anion (O2-) while native alpha 2-macroglobulin had little effect except at high concentration. The alpha 2-macroglobulin 'fast' forms, which bind with a Kd of about 8 nM, inhibited 50% generation of O2- (ID50) at a concentration of 7 nM while alpha 2-macroglobulin inhibited O2- production with an ID50 of 141 nM. The 'fast' forms of alpha 2-macroglobulin may play a role in the feedback regulation of inflammatory reactions.     

α2-macroglobulin ‘fast’ forms inhibit superoxide production by activated macrophages

Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human α₂-macroglobulin converted to its ‘fast’ form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both α₂-macroglobulin-trypsin and α₂-macroglobulin-methylamine inhibited macrophage production of superoxide anion (O₂⁻) while native α₂-macroglobulin had little effect except at high concentration. The α₂-macroglobulin ‘fast’ forms, which bind with a K_d of about 8 nM, inhibited 50% generation of O₂⁻(ID₅₀) at a concentration of 7 nM while α₂-macroglobulin inhibited O₂⁻ production with an ID₅₀ of 141 nM. The ‘fast’ forms of α₂-macroglobulin may play a role in the feedback regulation of inflammatory reactions.     

Hyperthyroidism with Periodic Paralysis

Hyperthyroidism may be associated with hypokalemic periodic paralysis. Two cases are presented demonstrating intermittent attacks of flaccid paralysis associated with clinical symptoms, signs and laboratory findings of hyperthyroidism. During an attack, one patient had a serum potassium of 2.1 mEq. per litre.Various factors such as trauma, exposure to cold, excessive carbohydrate ingestion and certain medications have been stated to precipitate an episode of paralysis. Attacks may range from mild weakness to generalized flaccid paralysis with loss of deep tendon reflexes. Several reported patients have died owing to cardiac arrest or respiratory paralysis.During attacks, the serum potassium is usually in the range of 2.2 to 3.2 mEq. per litre. It is postulated that a metabolic abnormality affecting the muscle-cell membrane can occur in the hyperthyroid state resulting in a shift of potassium to the intracellular position, thus producing a situation of hyperpolarization of the muscle-cell membrane which in turn alters the muscle contractibility.The importance of recognizing the unusual association of hypokalemic periodic paralysis with hyperthyroidism is stressed because, with successful treatment of the hyperthyroidism, the episodes of paralysis disappear.