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Biomedical subjects

J Verhoef

Publications and source records attributed to J Verhoef.

At least 541 records · Page 30Linked to original sources

Suppression of phagocytosis and chemotaxis by cell wall components of Staphylococcus aureus.

The ability of S. aureus to resist phagocytosis by polymorphonuclear leukocytes (PMN) is thought to be an important virulence factor for this microorganism. We have studied the effect of 3 major cell wall components of S. aureus, peptidoglycan, protein A, and teichoic acid, on PMN function. Phagocytosis and chemotaxis were both inhibited by prior incubation of PMN with peptidoglycan. This effect was dose- and time-related; incubation with as little as 2.5 micrograms/ml for 30 min produced a discernible suppressive effect. Suppression of PMN function was independent of the presence of human serum but was abolished by rabbit antiserum to peptidoglycan. Addition of peptidoglycan to PMN stimulated a prolonged chemiluminescence response that was greater when the peptidoglycan was first incubated in normal serum, perhaps reflection opsonization of this particulate material. Although protein A also suppressed phagocytic and chemotactic capabilities of PMN, this effect was observed only in the presence of serum and was eliminated by absorbing Ig. Centrifugation of the serum + protein A mixture showed that the suppressive effect was contained in the precipitated sediment. Complexes of Ig alone were not suppressive. Teichoic acid in concentrations less than or equal to 100 micrograms/ml had no adverse effect on PMN function. These studies describe ways in which peptidoglycan and protein A may interfere with phagocytosis and chemotaxis of human PMN, thus giving evidence for the role of these cell wall components as virulence factors.

Animals↗

Separation and quantification of angiotensins and some related peptides by high-performance liquid chromatography.

A high-performance chromatographic technique for the separation of angiotensins and some related peptides is described. Complete separation of angiotensin I, angiotensin II, tetradecapeptide and the tetrapeptide Leu-Val-Tyr-Ser is achieved in a single step, using reversed-phase high-performance liquid chromatography. The application of this technique for the detection of renin activity in crude biological samples, employing the artificial renin substrate tetradecapeptide, is demonstrated.

Angiotensin I↗

Selective conversion of beta-endorphin into peptides related to gamma- and alpha-endorphin.

beta-Endorphin (beta-LPH61-91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller beta-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of gamma-endorphin (beta-LPH61-77) by removing the N-terminal amino acid yielded des-tyrosine-gamma-endorphin (beta-LPH62-77, dT gamma E) which had greater behavioural activity than gamma-endorphin. The CNS effects of dT gamma E resembled those of neuroleptic drugs in several test systems. alpha-Endorphin (beta-LPH61-76) exerted effects opposite to those of dT gamma E and in some aspects its activity was comparable to that of psychostimulant drugs. This opposition of effects suggests that a balance between gamma- and alpha-type endorphins is involved in the control of brain function. We report here that either gamma-endorphin and dT gamma E or alpha-endorphin and des-tyrosine-alpha-endorphin (beta-LPH62-76, DT alpha E) can be formed preferentially from beta-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.

Animals↗

Interactions of phagocytic and bacterial cells in patients with bacteremia caused by gram-negative rods.

The phagocytic and bactericidal functions of polymorphonuclear leukocytes and monocytes and the opsonic activity of serum from patients with gram-negative bacteremia were compared with those of cells and serum from healthy donors and control patients. Leukocytes from five of 20 patients showed diminished phagocytic capacity. Leukocytes from three of 12 patients had decreased chemotactic activity. Eleven of 37 blood culture isolates were inefficiently phagocytized after opsonization in homologous patient serum. However, in no instance was the opsonic capacity of patient serum significantly lower than that of control serum. In the serum of some patients, an increase in heat-stable opsonins was found during the course of infection. Resistance to opsonization of strains of Escherichia coli correlated with the presence of K capsular polysaccharide. It was concluded that both impaired leukocyte function and ineffective opsonization play a role in the pathogenesis of gram-negative bacteremia. Heat-stable opsonins (presumably specific antibodies) appear to be necessary for effective phagocytosis of bacilli that cause gram-negative bacteremia.

Antigens, Bacterial↗

H-Pro-[3H]Leu-Gly-NH2: metabolism in human and rat plasma investigated by high-pressure liquid chromatography.

H-Pro-Leu-Gly-NH2 (PLG) was labeled with 3H-leucine by catalytic tritiation of H-Pro-methylallylgylcyl-Gly-NH2 and purified by ion-exchange chromatography. Metabolism of 3H-PLG in rat and human plasma was investigated by reversed phase-paired ion high-pressure liquid chromatography. All possible metabolites could be completely separated within 25 min. Half-lives, based on disappearance of intact 3H-PLG, for in vitro metabolism were 26.4 min (rat) and 5.6 days (human). The only significant metabolite was 3H-leucine. A rate-limiting, species-specific enzyme seems responsible for the initial breakdown of PLG. Disappearance of 3H-PLG from rat plasma, following i.v. administration, proceeded with half-lives of 1.03 min (distribution) and 9.8 min (elimination).

Animals↗

Phagocytic and chemotactic function of polymorphonuclear and mononuclear leucocytes in patients with recurrent staphylococcal infections.

From 21 patients with chronic or recurrent staphylococcal infections, phagocytosis and intracellular killing of Staphylococcus aureus by polymorphonuclear (PMN) and mononuclear (MN) leucocytes were evaluated. Also chemotactic responsiveness and the capacity of their sera to opsonize Staph. aureus was tested. The chemotactic, phagocytic and bactericidal capacity of PMN's and MN's from patients was significantly decreased. The mean uptake of Staph. aureus by patient PMN's and MN's was 65% and 44%, respectively, as compared to 85% and 75% observed with PMN's and MN's from 38 healthy donors. The phagocytic activity of 17/21 patients (81%) was below the normal range. A decreased chemotactic mobility and bactericidal capacity of patient leukocytes was also found and was always accompanied by a decreased rate of ingestion. Although a great variability was noted in the phagocytic capacity of leucocytes from patients tested repeatedly over periods up to 82 weeks, the mean value for phagocytosis remained below the normal range in 10/11 patients included in the follow-up study. Except for 1 patient with dysgammaglobulinemia, sera from the patients contained normal amounts of immunoglobulins and complement (CH50 and C3), and they all effectively opsonized Staph. aureus. The results indicate that defects in leucocyte function may be frequently involved in the pathogenesis of recurrent Staph. aureus infections.

Adolescent↗

Host-parasite relationship in staphylococcal infections: the role of the staphylococcal cell wall during the process of phagocytosis.

Evidence is presented that antibodies against staphylococcal peptidoglycan are important opsonins for phagocytosis of staphylococci. Cell wall protein A inhibits opsonization by IgG through its interaction with the Fc fragment of the IgG molecule and preventing therefore the binding between the Fc fragment and the Fc receptor of the cell membrane of the leukocyte. Extracellular protein A interferes with opsonization presumably through depletion of complement.

Antibodies, Bacterial↗

Endocarditis caused by coagulase-negative staphylococci.

Sixteen patients with coagulase-negative staphylococcal endocarditis were treated at the University of Minnesota Hospitals between January 1970 and September 1977. In six patients, endocarditis developed after prosthetic valve surgery; among the other ten patients (the medical group), eight had known antecedent valvular disease. The skin was thought to be the source of infection in eight patients, suggesting that prompt treatment of skin infections and avoidance of injections in patients with valvular disease are important measures in the prevention of this disease. Patients with prosthetic valve endocarditis were infected with antibiotic-resistant organisms and had a higher mortality than those in the medical group (83% versus 20%). Bacterial isolates from three patients with prosthetic valve endocarditis were resistant to methicillin, and two of these three isolates also were resistant to cephalothin by quantitative susceptibility testing. The only patient with prosthetic valve endocarditis to survive was operated upon early in the course of his illness. These observation, coupled with the high mortality in this series and in others, has prompted us to advocate early surgery in prosthetic valve endocarditis.

Adolescent↗

Escherichia coli K antigen in relation to serum-induced lysis and phagocytosis.

The presence of capsular polysaccharides (K antigens) and their relation to phagocytosis and sensitivity to the lytic action of serum of 26 strains of E. coli isolated from stools of healthy volunteers and from blood cultures were studied. Four of 12 strains isolated from stool cultures and 12 (86%) of the 14 strains isolated from blood cultures possessed K antigen. Three of the 12 strains isolated from stool cultures and seven of the 14 isolated from blood cultures were resistant to uptake by polymorphonuclear leucocytes; these resistant strains contained large amounts of K antigen. By contrast 10 strains, three with low amounts of K antigen and seven without detectable amounts of K antigen, were readily phagocytosed. Thus it appears that K antigen renders E. coli resistant to phagocytosis. Only four (15%) of the 26 strains were sensitive to serum lysis and there was no correlation between the presence of K antigen and the resistance to serum lysis.

Antigens, Bacterial↗