Defective cellular immunity in renal failure: depression of reactivity of lymphocytes to phytohemagglutinin by renal failure serum.

In defining host resistance factors in uremia, experiments were designed to assess the effect of renal failure serum upon the reactivity of normal human lymphocytes to phytohemagglutinin in vitro. Normal buffy coat cells were resuspended in sera obtained from normal subjects and from 14 patients with renal failure, then stimulated with phytohemagglutinin M and the cellular response measured by the increase in thymidine or uridine uptake. The mean thymidine uptake by stimulated cells in normal sera was 14,389 +/-1695 (SEM) cpm per 2 x 10(6) lymphocytes. Uridine uptake under the same conditions was 12,540 +/-1887 cpm. Compared to these are a mean thymidine uptake of 2740 +/-457 cpm and uridine uptake of 3928 +/-667 cpm in renal failure sera. Both differences are significant at P<0.01 level. For controls representing "chronic illnesses," sera from patients with pneumococcal meningitis, cirrhosis of the liver without jaundice, rheumatoid arthritis, and paraplegia with urinary tract infection did not cause suppression. No single drug had been taken by all the renal failure patients; three patients were taking no drugs. The serum from one patient with acute renal failure suppressed thymidine uptake while her serum obtained after recovery from her illness supported a normal lymphocyte response. Improvement of lymphocyte response was also noted in 9 of 10 sera obtained from patients immediately after hemodialysis. These observations plus the inhibition of stimulated cells by normal serum mixed with renal failure serum indicate the presence of a dialyzable inhibitory factor rather than the absence of a supporting factor in the renal failure sera. Lymphocytes preincubated for 24 hr in renal failure serum responded normally when transferred to normal serum and stimulated. Cells stimulated in normal serum and transferred to renal failure serum within the initial 24 hr of incubation demonstrated depressed thymidine uptake. Also, cell survival for 72 hr incubation as judged by trypan blue exclusion and chromium-51 release was similar in normal and renal failure sera. Thus, the suppressive effect of renal failure serum does not depend upon the initial phytohemagglutinin-cell interaction nor upon a significant cytotoxic effect. These studies demonstrate that a dialyzable factor(s) in the serum of patients with renal failure can greatly suppress one parameter by which an immune function of circulating lymphocytes is assessed and provides at least, a partial explanation for delayed homograft rejections in renal failure as well as the susceptibility of such patients to various infections.

Escherichia coli bacteremia in the squirrel monkey. I. Effect of cobra venom factor treatment.

Squirrel monkeys were significantly depleted of complement by a nontoxic protein constituent of cobra venom, and the influence of cobra factor (CoF) treatment on the course of Escherichia coli bacteremia was studied. Striking neutropenia occurred rapidly in control animals while the rate of occurrence of neutropenia was 20 to 30 times slower in the CoF-treated animals, suggesting that the E. coli-induced neutropenia was at least partially a complement-mediated response. In the CoF-treated monkeys, the initial rate of clearance of the E. coli from the circulation tended to be slower and the resultant levels of bacteremia were higher than in control animals. These observations are consistent with a hypothesis that complement-mediated neutrophilic leucocyte function is an important host defense mechanism in gram-ngeative bacillary bacteremia.

Adherence of bacteria to heart valves in vitro.

The abilities of 14 strains of aerobic gram-positive cocci and gram-negative bacilli to adhere in vitro to human or canine aortic valve leaflets were compared. 2-mm sections of excised valve leaflets were obtained by punch biopsy and were incubated under standardized conditions in suspensions of bacteria. Valve sections were subsequently washed and homogenized, and quantitative techniques were used to determine the proportions of bacteria from the initial suspensions that had adhered to the valve sections. Comparable results were obtained when these adherence ratios were determined by two independent methods based either on measurements of bacterial viability or of radioactivity in 51Cr-labeled bacteria. For each bacterial strain, the adherence ratio was constant over a wide range of concentrations of bacteria in the incubation medium. Strains of enterococci, viridans streptococci, coagulase-positive and coagulase-negative staphylococci and Pseudomonas aeruginosa (adherence ratios 0.003-0.017) were found to adhere more readily to valve sections than strains of Escherichia coli and Klebsiella pneumoniae (adherence ratios 0.00002-0.00004). The organisms that most frequently cause bacterial endocarditis were found to adhere best to heart valves in vitro, suggesting that the ability to adhere to valvular endothelium may be an important or essential charcteristic of bacteria that cause endocarditis in man.

Local immune response in experimental pyelonephritis.

Experiments using an in vitro method of assessing protein synthesis by (14)C amino acid incorporation were designed to determine whether pyelonephritic kidneys were capable of local antibody production. Unilateral pyelonephritis was produced in rabbits by intravenous injection of E. coli 0-75 while one ureter was transiently occluded. The capability of protein and immunoglobulin synthesis by pyelonephritic kidneys, contralateral kidneys, normal kidneys, and spleens from normal and pyelonephritic animals was measured. Enhanced protein and immunoglobulin syntheses by pyelonephritic kidneys were first detected by the 11th day after infection and persisted through day 120. In individual experiments the pyelonephritic kidney produced 6-170 times more soluble protein than did the contralateral, uninfected kidney. In seven experiments, IgG comprised a mean of 72% of the total protein synthesized by the pyelonephritic kidney, compared with a mean of 19% in the contralateral kidney. IgA accounted for 10 and 9%, respectively. In these experiments 0.6-17% of the synthesized IgG was precipitable by somatic antigen of the E. coli 0-75. The capability of the pyelonephritic kidney to synthesize soluble protein was quantitatively similar to that of spleens from infected animals. The proportion of synthesized protein which was immunoglobulin G, however, was greater in the pyelonephritic kidney than in the spleen. Furthermore, specific antibody synthesis by the pyelonephritic kidney persisted longer than did synthesis by the spleen of the same animal. These studies provide evidence that in experimental pyelonephritis a significant local immune response occurs which is represented primarily by the production of IgG. Local immunoglobulin formation and specific antibody synthesis may be important factors in determining patterns of host resistance.

Mouse asialoglycoprotein receptor cDNA sequence: conservation of receptor genes during mammalian evolution.

The asialoglycoprotein receptor internalizes galactose-terminated glycoproteins into mammalian hepatocytes for degradation in lysosomes. We report the cloning and sequencing of one murine asialoglycoprotein receptor cDNA which exhibits homology with rat and human receptor forms. Conserved regions may correlate with functional domains. The membrane-bound M (mouse) HL polypeptide does not contain a cleavable N-terminal signal sequence and is probably anchored to the membrane via an internal insertion sequence.

Brucella canis. A cause of undulant fever.

Brucella canis, recognized in 1967 as a cause of canine abortion, is an uncommonly recognized human pathogen. Our patient, a 48 year old man, probably acquired his infection by contact with an infected dog. His clinical course was characterized by intermittent fever and bacteremia over a 4 month interval. His course, which expands the clinical spectrum of human infections due to Br. canis, is discussed in the context of the other reported instances of community and laboratory acquired cases.

Self-help for the traveler who becomes ill.

While infections commonly occur in travelers, most can be prevented by avoiding fresh fruit (unless it is peeled), fresh vegetables, unpasteurized milk and cheeses, nonbottled water and ice; by taking antimalarial drugs; by using insect repellents in areas where indicated; and by using common sense. Remember also that travel does not prevent you from getting many of the illnesses you might get at home. It is essential to take any regular medications along with you. I recommend that you take such medications in your carry-on baggage, for airlines have a propensity for losing baggage that contains critical items. If you do become ill, you can take care of most illnesses yourself if you have planned ahead.

Medical Readiness Education and Training Exercises by United States Army medical personnel in Kenya.

Medical Readiness Education and Training Exercises (MEDRETEs) enable United States military medical personnel to sharpen their skills in diagnosis and treatment of common illnesses in rural third world populations. We report our experiences on MEDRETEs conducted during recent exercises in the Republic of Kenya involving United States and Kenyan forces. Respiratory, musculoskeletal, and eyes, ears, nose, and throat conditions comprised 55% of cases. In 73% of cases, the final diagnosis and the chief complaint were in the same diagnostic category. In asymptomatic patients, 17% had physical findings suggestive of significant disease. Anecdotal experiences demonstrated the importance of the local environment and social customs in the genesis of certain illnesses and symptoms.