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Biomedical subjects

J Falk

Publications and source records attributed to J Falk.

At least 37 records · Page 2Linked to original sources
PubMed1991

Conditioned taste aversion but not adrenal activity develops to ICV administration of interleukin-1 in rats.

In a previous investigation with mice, the paired presentation of either odor or taste cues with the peripheral (IP) administration of the immunoactive peptide interleukin-1 (IL-1) led to the conditioned enhancement of glucocorticoid production. The present study found that an initial central infusion of IL-1 in the presence of saccharin cues produced a robust taste aversion but not a conditioned elevation of either ACTH or corticosterone production. These results indicate that the glucocorticoid response induced by centrally administered IL-1 in rats is independent of the behaviorally aversive properties of this cytokine which are conditionable. The differential effects of IP versus ICV administration of IL-1 on glucocorticoid conditioning requires a clearer specification of the respective signaling mechanisms and pathways activated by these two routes of administration.

Adrenocorticotropic Hormone↗
PubMed1991

Interplay of microbe and major histocompatibility complex: a family study.

We describe a 24-year-old man who developed reactive arthritis (ReA) after a dysenteric illness caused by Salmonella hadar. Serologic tests suggested recent exposure of family members to Salmonella. All members of the family were HLA-B27 positive, but no other family member developed acute ReA, although 2 of them had clinical evidence of previously existing B27 associated arthritis.

Adult↗
PubMed1990

The Pavlovian conditioning of IL-1-induced glucocorticoid secretion.

Recombinant IL-1-beta, which is capable of stimulating the pituitary-adrenal axis to secrete corticosterone, was paired with environmental cues in either a taste aversion or odor conditioning procedure. Among mice receiving paired delivery of cues and IL-1, subsequent re-exposure to cues elicited corticosterone production. This response was significantly greater than in animals that were conditioned but not re-exposed to the cues or were exposed to the cues alone. These results indicate that the IL-1 activation of adrenal cortical secretion can be conditioned to environmental stimuli.

Animals↗
PubMed1990

The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection.

In renal transplantation, preformed cytotoxic antibody against donor HLA class I antigens causes hyperacute rejection of renal allografts, but its pathogenic significance when it develops in the posttransplant period is unknown. In the present studies we describe the clinical and pathologic features of patients with rejection associated with anti-class I. In the course of 400 consecutive cadaveric renal transplants, 7 patients were identified who had antibody against donor class I HLA antigens in association with atypical but distinctive patterns of rejection. All 7 were presensitized. In 3 patients, the transplant had been inadvertently performed with a positive donor-specific T cell crossmatch. In the remaining 4, the T cell crossmatch on current sera was negative but became positive posttransplant. The clinical picture was deterioration of graft function with rapid onset of oliguria, apparently due to acute tubular necrosis, but with persistence of blood flow demonstrable by radioisotope scan studies. Renal histology showed that the typical lesions observed in cell-mediated rejection, such as tubulitis and interstitial infiltration, were absent. Granular complement deposition (6), polymorphonuclear infiltration (6), and endothelial injury in the microvasculature (6) were common, and mononuclear infiltrates were absent (2) or not prominent (4). In 3 patients the glomerular changes resembled a picture of hemolytic uremic syndrome, with capillary fibrin thrombi and widening of the subendothelial space. IgG staining was negative. The pathologic features suggest that anti-class I antibody appearing or persisting in the early posttransplant period injures the endothelium of the microvasculature, with the clinical presentation different from that of hyperacute rejection. Particularly in sensitized patients, rapid deterioration in function, leading to a picture of acute tubular necrosis, with pathologic features of endothelial injury in the microcirculation, should suggest the diagnosis of anti-class I-mediated rejection.

Adult↗
PubMed1989

HLA class I-related impairment in IL-2 production and lymphocyte response to microbial antigens in reactive arthritis.

The contribution of certain Gram-negative bacteria and host HLA class I Ag to the development of reactive arthritis (ReA)3 has strong epidemiologic support but the pathogenesis of the arthritis is unknown. An outbreak of Salmonella typhimurium afforded the opportunity to compare the immune response to the organism between those who developed ReA (ReA+, n = 11) with those who did not (ReA-, n = 12). Of the 11 ReA+ patients, 4 were B27-positive and 6 were B7-positive; of the ReA- patients none was B27- or B7-positive. The causative pathogen S. typhimurium phage 22 was used to examine PBL proliferation by [3H]thymidine incorporation. Impairment in lymphocyte response to S. typhimurium in ReA+ compared with ReA- was demonstrated by: i) lower stimulation index (1.9 +/- 0.3 for ReA+, 5.7 +/- 0.6 for ReA-, p less than 0.01); ii) lower in vitro Ig production; and iii) lower Ag-induced IL-2 production. Mixing experiments did not demonstrate a soluble suppressor factor in ReA+ supernatants. Thus, after infection with S. typhimurium there is an impairment in cellular immunity that has correlates in immunogenetic and clinical features of the infected population.

Antibodies, Bacterial↗
PubMed1988

Postdysenteric reactive arthritis. A clinical and immunogenetic study following an outbreak of salmonellosis.

Following an outbreak of foodborne gastroenteritis caused by Salmonella typhimurium, questionnaires were sent to affected individuals and then to the family physicians of any who experienced extra-enteric complications. Of 260 individuals infected with S typhimurium for whom adequate data were obtained, 19 patients developed joint disease (7.3%). All were men; the mean age +/- SD was 39.3 +/- 1.6 years. Among the 16 patients for whom this information was available, the interval from the onset of diarrhea to the onset of joint pain was less than 7 days in 7, 8-21 days in 2, and greater than 21 days in 7. There was a significantly longer duration of diarrhea in those patients with joint disease (mean +/- SEM 15.2 +/- 2.6 days) than in those without complications (10.0 +/- 1.1 days) (P less than 0.01). The joint disease was monarticular in 3 patients and polyarticular in 16. The joints most commonly affected were the elbow (47%), wrist (47%), knee (42%), low back (32%), and shoulder (32%). Six of the 19 patients had at least 1 extraarticular feature: ocular (5 patients), mucosal (1 patient), urethral (2 patients), or cutaneous (1 patient). Of these 19 patients, 11 were located and agreed to HLA typing. Four were positive for HLA-B27, 6 were HLA-B7 positive, and 1 had HLA-Bw60. Of the 4 B27 positive patients, 3 were DR1 positive; of the 6 B7 positive patients, 5 were DR2 positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Prostaglandins inhibit proliferation of the murine P815 mastocytoma by decreasing cytoplasmic free calcium levels [( Ca+2]i).

Prostaglandins inhibit the proliferation of the murine P815 mastocytoma. The mechanism of this antitumour activity remains undefined. In several cell systems, the action of PGs is inhibited at the cell surface receptor by pertussis toxin likely through regulatory G proteins involved in the inhibition of adenyl cyclase or activation of phospholipase C. We therefore determined the effect of prostaglandins on the biochemical consequences of activation of these pathways; i.e. concentrations of cyclic AMP (cAMP) and cytosolic free Ca+2 concentrations [( Ca/2]i) respectively. PGD2 (6 ug/mL), PGE1 (10 ug/mL) and PGB1 (50 ug/mL) maximally inhibited (3H)-thymidine incorporation to DNA. PGF2 alpha did not affect DNA synthesis. PGE1 (10 ug/mL) induced a three fold increase in cAMP concentrations. In contrast, the other prostaglandins did not alter cAMP concentrations. Maximal growth inhibitory doses of PGD2, PGE1 and PGB1 decrease [Ca+2]i, as measured by the fluorescence of Indo-1, from 320 +/- 5 nM to 172 +/- 20 nM, 161 +/- 12 nM, and 151 +/- 18 nM respectively. PGF2 alpha did not alter [Ca+2]i. Therefore, in contrast to the effects on cAMP, the decrease in [Ca+2]i was concordant with the inhibition of DNA synthesis. This suggests that PGs may inhibit proliferation through decreasing [Ca+2]i in the P815 mastocytoma.

Algorithms↗
PubMed1988

Bacterial infectibility of chronically implanted endothelial cell-seeded expanded polytetrafluoroethylene vascular grafts.

Vascular prosthetic grafts become more resistant to infection as the interval between implantation and bacteremic challenge increases. Endothelial cell (EC) seeding of such grafts has been shown to improve measurably their ability to resist a bacteremic challenge several weeks after implantation, presumably by reducing the amount of thrombus-free area (TFA) on their luminal surface. However, no investigators have reported the impact of EC seeding on the ability of chronically implanted vascular prostheses to resist a late bacteremic challenge. Bilateral common carotid interposition grafts were placed in 15 adult mongrel dogs with a 4 mm internal diameter, experimental, expanded polytetrafluoroethylene (ePTFE) prosthesis. One animal died shortly after operation and the grafts in two dogs thrombosed, thereby leaving 12 animals with at least one patent graft for subsequent study. At a mean interval of 45 weeks after implantation, five dogs (seven patent grafts) were challenged with an intravenous infusion of 3 X 10(8) radiolabeled Staphylococcus aureus; bacterial adherence and the TFA of the graft's luminal surface were determined for each of the patent grafts. There was no statistically significant difference in bacterial adherence or TFA between EC-seeded and control grafts. At a mean interval of 53 weeks after implantation, the remaining seven dogs (14 patent grafts) received a similar bacterial infusion and the animals were allowed to recover. Five days later, the grafts were harvested and cultured. Once again, there was no significant difference in the infectibility of EC-seeded vs. control grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Anticonvulsant-induced marrow suppression and immune thrombocytopenia.

Phenytoin and carbamazepine are rarely associated with serious hematologic side effects but can include impairment of either humoral or cell-mediated immunity. We describe a patient who developed severe granulocytopenia while taking phenytoin. The phenytoin was replaced by carbamazepine and the patient subsequently developed erythroid hypoplasia, neutropenia and persistent thrombocytopenia. In vitro studies demonstrated a phenytoin-dependent antigranulocyte antibody directly implicating phenytoin in the leukopenia. An extremely high titre of platelet-associated IgG was found which was independent of the presence of carbamazepine. Autoantibodies directed against the patient's red cells, granulocytes and lymphocytes were also demonstrated. In vitro marrow culture studies failed to detect cellular or humoral inhibitors and were suggestive of a stem cell defect. These studies indicate that anticonvulsant therapy can result in sustained humoral abnormalities as well as in nonimmune mediated marrow suppression.

Antigen-Antibody Complex↗
PubMed1988

The sensitized patient. A single center study.

1. In a 20-year period from 1966 to 1986, 650 renal transplants have been performed at the Toronto Western Hospital (University of Toronto). The 10-year actuarial patient survival is 62% and the actuarial graft survival is 35%. 2. A multivariant analysis using the Cox proportional hazard model indicated recipient age, donor source, graft number and time period were factors which independently influenced patient survival and that age and time period were variables which independently effected graft outcome. 3. Sensitization alone, using either peak or current PRA, did not significantly influence graft survival. Sensitization interacting with gender did affect graft survival, which was significantly lower in female patients with a high current PRA. Sensitization interacting with age produced different effects in the younger and older patients. The highly sensitized older patient has a better survival than the highly sensitized younger patient. However, for less sensitized patients the reverse was found; younger patients had a better survival than older patients. Also increasing levels of sensitization correlated with decreased survival in younger patients. 4. Predictive models based on the survivorship analysis of Kalbfleisch and Prentice were constructed to illustrate the impact of these variables on outcome.

Actuarial Analysis↗
PubMed1987

Immunochemical analysis of immune response to Chlamydia trachomatis in Reiter's syndrome and nonspecific urethritis.

Chlamydia trachomatis (Ct) has been proposed as a causative agent in Reiter's syndrome (RS) when an infection occurs in a susceptible host. To assess whether this susceptibility is reflected in a characteristic humoral immune response we compared patients with complicated (RS) and uncomplicated courses of nonspecific urethritis (NSU). Geometric mean titres of antibodies to C. trachomatis by immunofluorescence were 89.6 for RS, 80.0 for NSU and 16.0 for normals. 125I-Protein A probing of immunoblotted antigens of C. trachomatis revealed no band unique to RS. 125I-anti-IgA probing of immunoblots demonstrated reactivity with the 59,000 dalton antigen in 11/11 RS and 2/6 NSU. The major outer membrane protein of C. trachomatis (40,000 daltons) bound immunoglobulin nonspecifically. There was no clearly differentiating feature between HLA-B27-positive and B27-negative RS. One sequentially studied patient revealed an augmentation in synovial fluid IgA reactivity during the course of disease. No pattern of humoral immune response to C. trachomatis could be regarded as specific for RS nor for HLA B27-positivity. The study did not identify a Reiter's-specific antigen in C. trachomatis but demonstrates the usefulness of applying blotting techniques to population studies of HLA modulation of immune response to infectious agents.

Adult↗
PubMed1986

Molecular mimicry in Reiter's syndrome: cytotoxicity and ELISA studies of HLA-microbial relationships.

The pathogenic links between HLA antigens, certain bacterial infections and arthritis have not yet been characterized. The hypothesis of cross-reactivity between HLA B27, the marker of disease susceptibility for these disorders, and the provocative microorganism has been suggested by studies of Klebsiella and ankylosing spondylitis. The present study examines the possibility of molecular mimicry between HLA B27 and two organisms implicated more directly in reactive arthritis, Yersinia enterocolitica and Chlamydia trachomatis. Antibodies against these organisms were obtained both from patients and from antisera raised in rabbits. Neither source of antibacterial antibody was specifically cytotoxic for HLA B27-positive lymphocytes, even when the target cells were derived from patients with recent infections due to these organisms. In addition, monoclonal antibodies against HLA B27 (M1 and M2) showed no reactivity with antigens from these organisms in an ELISA system. These data do not support the notion of molecular mimicry as being the basis of immunogenetic susceptibility to reactive arthritis and Reiter's syndrome following infections with Y. enterocolitica and C. trachomatis.

Antigens, Bacterial↗
PubMed1986

Prevention of cyclosporine (CyA) nephrotoxicity by synthetic prostaglandins.

Acute and chronic nephrotoxicity directly attributable to cyclosporine (CyA) administration remains an obstacle to its successful use. The studies presented in this report characterize the cytoprotective properties of 16,16-dimethyl prostaglandin E2 in a lethal CyA-induced nephrotoxic rodent model. Wistar-Furth rats (200-250 g) receiving CyA alone (100 mg/kg/day) showed marked deterioration in renal function with severe histologic renal lesions and death of the majority of animals by day 7. The prostaglandin treated group (10/micrograms/kg/day) administered concomitantly with CyA demonstrated near normal renal function and histology by the eighth day after CyA discontinuation, and in a significant improvement in animal survival of 85% (p less than 0.001, n = at least 20 rats/group). These studies demonstrate a novel approach to a major problem with cyclosporine and should have exciting clinical potential.

Animals↗