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Biomedical subjects

J A Smit

Publications and source records attributed to J A Smit.

At least 37 records · Page 2Linked to original sources

Enhanced spontaneous and induced LAK function in baboons receiving total lymphoid irradiation (TLI).

TLI has potent immunosuppressive effects, but there is concern over its possible carcinogenic properties. The aim of the study was to assess to what degree TLI may compromise natural killer (NK) and lymphokine activated killer (LAK) cell function. There was a significant increase (P less than 0.0001) in both NK-cell function (measured against K562 targets) and spontaneous LAK-cell function (measured against DAUDI targets) in fresh blood lymphocytes throughout a course of 8 x 100 cGy fractionated TLI. This may be related to a three- and sevenfold increase, respectively, in CD16+ CD8- and CD56+ CD2- cell frequencies over the same period. Mitogen-induced interleukin 2 (IL-2) synthesis from blood lymphocytes was inhibited by up to 75% with as little as 100 cGy of TLI. Expression of IL-2 receptors on fresh lymphocytes did not vary and remained low. Therefore spontaneous LAK occurrence appeared to be triggered through an IL-2-independent pathway. The in vitro addition of IL-2 verified that cells retained their ability to respond to this lymphokine resulting in greatly enhanced induced LAK function. This was most probably mediated by CD56+ cells which were found to readily express IL-2 receptors upon mitogen stimulation. In conclusion, fractionated low-dose TLI appears to enhance MHC unrestricted immune surveillance in a manner independent of IL-2 production.

Animals↗

The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome.

The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%.

Adolescent↗

Charge formation in microporous membranes by single-acid site dissociation.

The electrolyte concentration and pH dependence of the effective charge density of weak ion exchange membranes have been studied by combining solutions of the Poisson-Boltzmann equation in cylindrical pores with a simple dissociation equilibrium of weakly acid groups attached to the pore walls. Analytical expressions for the effective charge density and wall potential are presented which describe these quantities in terms of pH, electrolyte (1 : 1) concentration, acid constant, density of acid groups and the pore size. The concentration dependence of the effective fixed charge density experimentally observed for cellulose membranes and NaCl-solutions agrees quantitatively with the theoretical predictions. For track-etched mica membranes and KCl-solutions the influence of pH and electrolyte concentration on the effective charge density can be qualitatively explained. Also an interpretation of electro-osmotic findings obtained with an asymmetric cellulose acetate membrane and NaCl-solutions is given.

Journal Article↗

Immunological compatibility between the chacma baboon and man.

Predictions of an increasing shortage of donor organs for the future has led to a resurgence of interest in xenotransplantation. We have methodically assessed the immunological compatibility of humans against the chacma baboon with a view to narrowing the gap of concordance by careful immunological screening. The necessity of major blood group compatibility in xenotransplantation is now established. While no group O universal donor exists in the baboon, groups A (45%), B (15%), and AB (40%) are well represented. Baboon histocompatibility antigens could not be precisely defined using human antisera. This does not necessarily imply lack of homology between the species, as we have shown specific crossreactivity of numerous antihuman monoclonal antibodies with baboon leukocytes. Normal humans do not exhibit preformed agglutinins to erythrocytes of the chacma baboon (Papio ursinus orientalis)) but cytotoxic antibodies are occasionally found. Sera from allosensitized patients may contain crossreacting hemagglutinins, leukoagglutinins and complement-dependent cytotoxic antibodies. Binding of human immunoglobulin-G and -M to baboon targets was demonstrated by flow cytometry. Negative crossmatch combinations for antibodies of the IgG subclass were easily found, but IgM antibodies from allosensitized patients were polyspecific in their action. In vitro assessment of lymphocyte mediated cytotoxicity showed that preformed cellular immunity between the species was rare. The response of human lymphocytes to xenoantigen stimulation in mixed lymphocyte cultures showed a normal distribution, permitting the selection of low-responding combinations. Screening for viruses, especially HTLV-1 and Coxsackie-BL34, is important. These findings demonstrate a closer degree of concordance than has previously been suspected.

Animals↗

Effects of experimentally induced Pasteurella haemolytica infection in dairy calves on the pharmacokinetics of flumequine.

The effect of experimental Pasteurella haemolytica infection on the intravenous and intramuscular pharmacokinetics of flumequine was studied in dairy calves. The plasma concentration-time curve of flumequine after intravenous injection of 5 mg/kg bodyweight flumequine of a 10% solution before and after experimental infection, was best described by a three-compartment open model. After intramuscular injection of the same dosage rate of a 3% flumequine suspension is was best described by the one-compartment open model with first-order absorption. The experimental infection by intratracheal administration of infectious bovine rhinotracheitis (IBR)-virus and 5 days later intrapulmonary administration of Pasteurella haemolytica produced a clear temperature rise and signs of disease expressed as Average Health Status. Subsequently, plasma Fe and Zn concentration decreased after infection. The distribution volumes Vc, Vd(area) and Vd(ss) after infection (0.07 +/- 0.04, 1.38 +/- 0.36 and 0.50 +/- 0.11 l/kg, respectively) were smaller than those before infection, but the differences were not significant (P less than or equal to 0.1). The intravenous AUC infinity was significantly increased (21.86 +/- 3.51 to 33.85 +/- 2.97 mg.h/l, P less than or equal to 0.01) and the total body clearance (ClB) significantly decreased (0.24 +/- 0.02 to 0.15 +/- 0.01, P less than or equal to 0.01) after infection. After intramuscular injection of flumequine at 5 mg/kg as a 3% suspension, only the bioavailability, F, was significantly decreased after infection (78.5 +/- 14.3 to 59.7 +/- 21.2%, P less than or equal to 0.02). However, this had no consequences for the dosage regimen used. The urine concentration ratio flumequine:7-hydroxy-flumequine:conjugated flumequine changed from 2:1:10 before infection to 6:1:15 after infection, which indicates that hydroxylation and glucuronidation as metabolic pathways for flumequine were decreased after Pasteurella sp. infection.

Animals↗

Growth of Escherichia coli in milk from endotoxin-induced mastitic quarters and the course of subsequent experimental Escherichia coli mastitis in the cow.

The objective of this study was to assess growth of Escherichia coli in milk from endotoxin-induced mastitic quarters and to relate the in vitro findings to the course of experimental E. coli mastitis. Whole and skim milks from 24 rear quarters of 12 cows were inoculated with E. coli 0:157 and incubated at 38 degrees C. Growth of E. coli 0:157 was not inhibited in milk collected from rear quarters immediately prior to endotoxin infusion. However, growth inhibition occurred in all but one whole mastitic milk samples collected from mastitic quarters 18 h after infusion of .1 mg of endotoxin. Skim milk samples from mastitic quarters were bactericidal in four cows (7 quarters), whereas growth occurred in skim mastitic milk from 17 quarters of nine cows. Rear quarters of all cows were inoculated with 10(4) cfu of E. coli 0:157 19 h after the quarters had been infused with endotoxin. Clinical parameters and milk production were monitored during 36 h and 21 d, respectively. None of the inoculated quarters developed signs of inflammation, and secreta from inoculated quarters were bacteriologically negative after 48 h. Therefore, growth-inhibitory property of skim milk from endotoxin-induced quarters was apparently not a suitable parameter to monitor differences in susceptibility to E. coli mastitis.

Animals↗

Intramammary infections and risk factors for clinical mastitis in herds with low somatic cell counts in bulk milk.

Ten herds with low somatic cell counts in bulk milk had an incidence of clinical mastitis of only 2.2 per 100 cows whereas 10 other herds with similarly low cell counts had an incidence of 53.6 per 100 cows. The major pathogens in the herds with a high incidence were Escherichia coli, Streptococcus uberis, Staphylococcus aureus and the coagulase-negative staphylococci. The percentage of uninfected quarters in the herds with a high incidence of clinical mastitis was 21.4 per cent compared with 12.2 per cent in the herds with a low incidence of clinical mastitis. The prevalence of coagulase-negative staphylococci, Corynebacterium bovis and Micrococcus species was higher in the herds with a low incidence of clinical mastitis. There was a significant linear relationship between the percentage of uninfected quarters and the incidence of clinical mastitis in the herds with a high incidence of clinical mastitis. In herds with a low incidence of clinical mastitis significantly less teat disinfection after milking was practised. The results suggest that infections with minor pathogens tend to protect cows against mastitis, and that teat disinfection after milking may increase the percentage of uninfected quarters and lead to an increased risk of clinical mastitis in herds with low somatic cell counts in bulk milk.

Animals↗

The intra- and inter-individual variability and reliability of transepidermal water loss measurements.

An analysis of variance was conducted to estimate the intra- and inter-individual variations in TEWL on the forearms, by sites (8 measurement sites) and by days (10 different days), in 30 non-exposed healthy individuals. The estimated intra- and inter-individual variations, by sites, were 15.5% and 84.5%, respectively, the sum of the 2 components always being 100%. With the exclusion of the 2 most distal sites near the wrist, which had significantly higher baseline TEWL values and fluctuations in TEWL, an improvement in the intra-individual variation was obtained. Thus, of the 6 sites, the estimated intra- and inter-individual variations were 8.4% and 91.6%, respectively. This finding supports the exclusion of these most distal sites for future investigations. The estimated intra- and inter-individual variations, by days, were 20.6% and 79.4%, respectively. The low site-to-site (8.4%) and day-to-day (20.6%) intra-individual variations, as compared to the large inter-individual variations of the same (91.6% and 79.4%), indicate that baseline TEWL is a stable personal characteristic. Thus, individual susceptible to irritant contact dermatitis (ICD), due to occupational exposure, may be reliably characterized by utilizing their baseline TEWL values, for "prediction" of risk in epidemiological field studies.

Adult↗

Effect of freezing on bacteriologic culturing of mastitis milk samples.

The objective was to determine the effect of freezing and length of freezing in a commercial freezer on the qualitative results of bacteriologic culturing of milk collected from glands of cows with clinical or subclinical intramammary infections. A total of 182 milk samples from cows with clinical mastitis and 55 milk samples of cows with subclinical mastitis were taken from four problem herds. Samples were split into four equal sub-samples. Three of these were frozen immediately at -20 degrees C and 1 was submitted fresh for bacteriologic analysis. At 4, 8, and 16 wk after collection, samples were thawed and submitted for bacteriologic culturing. Freezing and increased length of storage resulted in 1) a decrease in the number of samples that had cultures of Escherichia coli or Actinomyces pyogenes; and 2) an increase in the number of samples that had cultures of coagulase-negative staphylococci. Freezing had no effect on streptococci and Staphylococcus aureus.

Actinomyces↗