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Biomedical subjects

J Korn

Publications and source records attributed to J Korn.

At least 19 recordsLinked to original sources

Embryonic central nervous system angiogenesis does not involve blood-borne endothelial progenitors.

We asked, whether, in the blood of avian embryos, endothelial precursor cells circulate that actually contribute to the growing vascular system in and around the central nervous system (CNS). We compared the morphology and distribution of QH1-positive cells after transplantation of quail paraxial mesoderm, after blood transfusion, in quail-chick parabiosis, or after quail bone-marrow transplantation. After head mesoderm transplantation from quail to chick, we observed sprouting endothelial cells (ECs), capillary tube formation, and chimeric endothelial lining of large arteries in the host brain. These QH1-positive quail cells showed EC morphologies that demonstrated three different aspects of CNS angiogenesis: invasion by means of filopodia, clonal proliferation and tube formation, and integration into preexisting EC layers. After blood transfusion or in chick-quail parabiosis, blood-borne QH1+ cells were found in the lumen of but not integrated into the wall of the host vascular system. Neither were QH1+ cells observed in the capillary walls of parabiotic chick chorioallantoic membranes. In both cases, the quail cells showed typical macrophage morphology. In chicks that had received quail bone marrow transplants onto their chorioallantoic membranes, QH1+ cells with macrophage, but not EC shape were occasionally seen near the inoculation site. We conclude that (1) blood-borne cells do not become ECs or directly contribute to angiogenesis inside, or in vascular plexuses around the CNS during embryonic development; (2) blood-borne cells do not contribute to the intraneural macrophage population of the embryonic CNS.

Afferent Pathways↗

Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis.

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints. The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed. This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 microg/kg of rhIL-11 or placebo twice per week or 5 or 15 microg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug. Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 microg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response. The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

Adult↗

Suprathreshold repetitive transcranial magnetic stimulation elevates thyroid-stimulating hormone in healthy male subjects.

Repetitive transcranial magnetic stimulation (rTMS) has been introduced as a new antidepressive treatment strategy. The mode of action by which the antidepressive effect is brought about is not yet clear. Other antidepressive treatment strategies such as sleep deprivation are associated with an increase of plasma thyroid-stimulating hormone (TSH) levels that correlate with clinical improvement. In the present study, the effect of left prefrontal suprathreshold (120% of motor threshold) rTMS on TSH plasma levels of 19 healthy male subjects was investigated in comparison with subthreshold (80% of motor threshold) and sham stimulation. Suprathreshold rTMS was followed by a significant relative increase of TSH levels 10 and 60 minutes after stimulation in comparison with subthreshold and sham stimulation. The more pronounced effect of suprathreshold rTMS on TSH plasma levels might be important for the determination of optimal stimulation parameters in the treatment of depressed patients.

Adult↗

Experiments on the induction of antibody dependent macrophage-mediated cellular cytotoxicity in mixed brain cell cultures.

These examinations were based on the discussion whether in demyelinating diseases anti-lipid antibody associated with brain macrophages could have a cytotoxic effect on oligodendrocytes. We used mixed brain cell cultures of newborn rats where, among others, both oligodendrocytes and vacuolated macrophage-like cells were found. On these macrophage-like cells, the presence of Fc-receptors was proven. Besides Fc-receptor-dependent phagocytosis, these cells showed an Fc-receptor-independent type of phagocytosis. The Fc-receptor-bearing cells moved within the culture and adhered to glass fibers. In the cytoplasm of these cells, unspecific esterase, acid phosphatase and peroxidase could be visualized. The vacuolated cells showed strong autofluorescence, expressed a surface marker found on all types of rat leukocytes and were marked by Griffonia simplicifolia lectin. These results definitely characterized the vacuolised cells as macrophages. We saw globular and pleomorphic macrophages. After incubation of anti-GC serum in a highly diluted solution, significantly more macrophages bound to oligodendrocytes than in the controls. In these cases, we found target cell lysis. It could be shown in vitro that anti-GC serum together with macrophages of neonatal brains can induce a cytotoxic effect on oligodendrocytes.

Acid Phosphatase↗

Influence of a preventive care educational intervention on physician knowledge, attitudes, beliefs, and practice.

We evaluated the effect of a three-part intervention on knowledge, attitudes, beliefs, and practices relevant to preventive care. A group of 13 second-year internal medicine residents (Group I) were exposed to a lecture, chart-based reminder, and biweekly feedback during a 3-month ambulatory care rotation. The remaining two groups of residents (Group II, n = 12; Group III, n = 11) were not exposed to the intervention. We performed a chart review to assess preventive care practice at a clinical site separate from the intervention and surveyed residents to assess preventive care knowledge, self-reported practice, professional attitudes, and health beliefs. Chart reviews revealed the intervention to be associated with improved performance of preventive care (0.52 vs 0.35 and 0.42, P = 0.01). In addition, the intervention was associated with improved scores for preventive care knowledge (90 vs 74 and 77, P = 0.001) and self-reported practice (85 vs 65 and 72, P = 0.007). Although attitudes toward prevention and health locus of control were not measurably influenced by the intervention, stepwise multiple linear regression analysis demonstrated these factors to be independently related to preventive practice. Our data support the notion that physician preventive practice is subject to a variety of influences involving not only knowledge, and practice environment, but also training, professional attitudes, and health beliefs.

Ambulatory Care↗

Low-dose methotrexate treatment of rheumatoid arthritis. Long-term observations.

Of 21 patients with rheumatoid arthritis who began to receive low-dose weekly methotrexate up to five years ago, 15 (71 percent) have continued to take this drug for a mean of 42 months and have received a mean total dose of 2,021 mg (range: 915 to 3,075). The clinical improvement noted at the first follow-up (11 months) was sustained throughout this follow-up period (42 months). Three patients (14 percent) have had complete clinical remission and nine others (43 percent) have had an excellent response. Methotrexate was discontinued in four patients between the first and second follow-up because of planned pregnancy (one), gastrointestinal toxicity (two), and fear of toxicity (one). Liver toxicity assessed in these 21 patients and four others receiving long-term methotrexate therapy revealed acute hepatitis in one and elevated transaminase levels in 12 (48 percent). Liver biopsy specimens in 17 patients after a mean of 1,950 mg of methotrexate (range: 915 to 3,125) revealed mild fibrosis in six and no cirrhosis. Methotrexate can continue to suppress rheumatoid synovitis over a prolonged period of time with minimal toxicity in most patients. Hepatic fibrosis and cirrhosis due to methotrexate may be less common in rheumatoid arthritis than has been reported in psoriasis.

Arthritis, Rheumatoid↗

Sephadex-gel filtration (SGF) in infant and adult Gunn rats.

SGF was compared in infant and adult homozygous Gunn rats. Without any drug application, the test was negative in the adult animals, whereas a remarkable percentage of positive SGF was obtained in 5-7-day-old rats, especially in those undernourished and/or intensely icteric. Unexpectedly, in infant rats the rate of positive SGF after sulfadimethoxine injection was lower than in the untreated control group. Moreover, in 9-10-day-old animals who had positive SGF before the injection, the test became negative 15-20 min after sulfadimethoxine application in vivo. No convincing explanation could be given, but drug interference with the binding capacities of the Sephadex column could be excluded by appropriate in vitro tests.

Age Factors↗

Fenmetozole in acute alcholol intoxication in man.

Forty healthy adult male volunteers were studied to determine the efficacy of fenmetozole to antagonize the effects of acute alcholol intoxication. Twenty subjects receive placebo and 20 fenmetozole in dosage of 100 mg and 200 mg in a double-blind paradigm. Pretreatment with fenmetozole failed to antogonize or attenuate cognitive, perceptual, motor and affective changes associated with acute alchol intoxication.

Adult↗