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N Novak

Publications and source records attributed to N Novak.

At least 37 records · Page 2Linked to original sources
PubMed2001

Human epidermal Langerhans' cells are targets for the immunosuppressive macrolide tacrolimus (FK506).

BACKGROUND: The immunosuppressive macrolide tacrolimus (FK506) has been shown to inhibit allergic contact dermatitis in animal models as well as in human beings. More recently, successful treatment of atopic dermatitis with an ointment containing tacrolimus has been reported. OBJECTIVES: We explored the effects of this compound on epidermal Langerhans' cells (LCs), which are known to play an important pathophysiologic role in inflammatory skin diseases. METHODS: The expression of the intracellular FK506 binding protein (FKBP12) was monitored on freshly isolated and cultured epidermal LCs. Phenotyping and functional exploration of LCs treated with different concentrations of tacrolimus and beta-methasone valerate (betaMv) were performed. RESULTS: FKBP12 is expressed in freshly isolated LCs but is lost while they are maturating into mature dendritic cells. Tacrolimus inhibited the expression of IL-2R (CD25) and of the costimulatory molecules CD80 (B7.1) and CD40. Expression of MHC class I and II was also affected, whereas CD86 (B7.2) expression was not altered. In contrast, betaMv strongly increased the expression of CD25. Paradoxically, while decreasing CD40 and MHC class I expression, betaMv significantly increased the expression of MHC class II, CD80, and CD86 on cultured LCs but impaired their allostimulatory activity. Tacrolimus was about 100 times more potent than betaMv at inhibiting LC stimulatory function. CONCLUSION: Tacrolimus can exert immunopharmacologic alterations on LCs, which may account, at least in part, for the therapeutic effect of this compound in eczematous skin diseases.

Administration, Topical↗
PubMed2001

Standardized extracts from Chinese herbs induce IL-10 production in human monocyte-derived dendritic cells and alter their differentiation in vitro.

BACKGROUND: The efficacy of traditional Chinese medicine (TCM) as a treatment for atopic dermatitis has been evaluated in clinical trials. Until now, the underlying mechanism of this treatment has remained completely elusive; this is particularly true of its putative effects on dendritic cells (DCs), which might play a pivotal role in the disease. OBJECTIVE: We investigated the influence of a standardized extract from 10 Chinese herbs that was successfully used in clinical trials on the generation of monocyte-derived DCs from atopic donors. METHODS: Detailed phenotypic and functional exploration of DCs generated in the presence of IL-4 and GM-CSF and treated with different concentrations of TCM or a placebo control was performed. RESULTS: TCM profoundly affected the morphology and phenotype of the developing DCs. They lost their typical dendritic morphology and decreased their expression of CD1a as well as the low-affinity IgE receptor CD23. Most importantly, TCM-exposed DCs exhibited a diminished stimulatory activity toward autologous antigen-specific and allogeneic T cells while secreting high amounts of IL-10. CONCLUSION: TCM induces immunopharmacologic alterations on DCs from atopic donors in vitro. These alterations might account, at least in part, for the therapeutic effect of this treatment in AD in vivo.

Dendritic Cells↗
PubMed2000

[Benign symmetrical Launois-Bensaude type II lipomatosis with market systemic involvement and psoriasis].

Benign symmetric lipomatosis of the pseudoathletic type was identified in a woman with a positive family history for the disorder and a past history of alcohol abuse. She had an exceptionally high number of additional diseases such as arthropathy with degenerative osteoporosis, hyperuricemia, hyperlipidemia, psoriasis, neuropathy, muscular atrophy, arteriosclerosis and increased cardiovascular risk factors.

Comorbidity↗
PubMed1997

Severe disease in children with trachoma is associated with persistent Chlamydia trachomatis infection.

The immediate study objective was to determine if variable disease severity in children with trachoma could be attributable in part to host variation in the ability to clear Chlamydia trachomatis infection. Identification of sibling cohorts with these variant phenotypes would be useful for immunogenetic studies. A weekly survey for 3 months in a trachoma-hyperendemic village using detection of chlamydial DNA and grading of disease severity indicated that 62% (33/53) of children had at least one infection episode. Of those, 64% (21/33) who were persistently infected had both significantly higher mean chlamydial DNA loads and more severe trachoma than did sporadically infected children. Of importance, duration of infection differed between siblings in 60% (6/10) of families. The results suggest that chlamydial load and duration of infection determine the chronic nature of severe disease in trachoma and that host variable efficiency for chlamydial clearance between siblings is in part determined by host variation.

Adenoviruses, Human↗
PubMed1996

Evidence for a predominant proinflammatory conjunctival cytokine response in individuals with trachoma.

Immune responses to Chlamydia trachomatis infection in trachoma do not protect against reinfection or the development of scarring and blindness. In addition, the immunoregulatory contribution of cytokines to the development of conjunctival histopathology or protection is undefined. In this study, conjunctival cytokine mRNA transcripts were compared among subgroups of chlamydia infection status and ocular disease presentations of 50 individuals from an area where trachoma is endemic. There was a significant association of elevated interleukin (IL)-1beta, transforming growth factor beta1, and tumor necrosis factor alpha transcripts with infection, follicular inflammation, and scarring. Both gamma interferon (IFN-gamma) and IL-2 transcripts were significantly associated with infection; slightly elevated IL-2 levels were found in inflammatory disease. High IFN-gamma transcript levels were present with follicles and inflammatory disease and to a lesser extent with inflammatory scarring. The role of IFN-gamma in protection from infection or disease was not apparent from this study, since transcripts were frequently present in both chlamydial infection and disease. IL-12 (p40) transcripts were elevated in adults and children in association with follicular inflammation but not with scarring. IL-4, IL-5, and IL-10 transcripts were not detected in any samples. In conclusion, C. trachomatis infection stimulates local cytokines which favor a strong cell-mediated and proinflammatory response in both the early and later manifestations of trachoma. In addition, cytokine transcript levels that were associated with disease but no infection were characteristically lower overall than when chlamydia was present.

Adult↗
PubMed1993

Formation of specific efferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus and superior colliculus.

Cells in the cerebral cortex project to many distant regions in the brain. Each cortical target receives input from a specific population of cells which have a characteristic morphology and which are located in a distinct cortical layer. In an attempt to learn about the mechanisms by which this stereotypic output pattern is generated during development, we have studied the formation of cortical projections in an in vitro system. Slices from developing rat visual cortex were cocultured with slices from the superior colliculus, the major target of cells in layer 5, and the lateral geniculate nucleus, the major target of cells in layer 6. Cortical neurons which established connections with tectal and thalamic explants were retrogradely labelled with fluorescent dyes. It was found that, in vitro, different populations of neurons project to these two targets, and that the laminar position and cellular morphology of the projecting cells were similar to their in vivo counterparts. These specific connections were established when the target explants were placed either next to the white matter or next to the pial side of cortical slice cultures. The axons of cells projecting to ectopic positioned explants reoriented their trajectories and grew through the cortical grey matter directly towards their targets. Thus subcortical targets exert an orienting effect specifically on their innervating cells and attract growing axons of the appropriate cells at a distance. These results suggest that different targets release different molecules that act selectively on specific populations of neurons. Therefore, chemotropic guidance is likely to play a significant role in the development of specific connections between cortical neurons and their target areas.

Animals↗
PubMed1993

Reconstructing cortical connections in a dish.

During development of the cortex, efferent projection neurons located in distinct cortical layers send their axons to different targets, and afferent fibers establish connections with cortical target cells of a particular layer. Recent studies have shown that layer- and cell-specific afferent and efferent cortical connections established in culture are similar to those observed in vivo. The results of these experiments provide evidence for the existence of diffusible and membrane-bound guidance factors for specific sets of axons. Furthermore, they suggest the use of different molecules to navigate axons towards their target, regulate target innervation and mediate target cell recognition.

Animals↗
PubMed1992

Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus.

The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development.

Afferent Pathways↗
PubMed1990

Formation of target-specific neuronal projections in organotypic slice cultures from rat visual cortex.

A characteristic feature of the mammalian cortex is that projection neurons located in distinct cortical layers send their axons to different targets. In visual cortex, cells in layers 2 and 3 project to other cortical areas, whereas cells in layers 5 and 6 project to subcortical targets such as the lateral geniculate nucleus. The proper development of these projections is crucial for correct functioning of the visual system. Here we show that specific connections are established in an organotypic culture system in which rat visual cortex slices are co-cultured with another slice of the visual cortex or with a thalamic slice. The laminar origin and cellular morphology in vitro of cortical projections to other cortical regions or to subcortical targets are remarkably similar to those seen in vivo. In addition, axons of projecting cells are not restricted to particular pathways, but appear instead to grow directly towards their appropriate target. These observations raise the possibility that chemotropic attraction from the target areas may play an important part in the development of the cortical projection pattern.

Afferent Pathways↗
PubMed1989

[Acetylcholinesterase negativity in the lamina propria in the first 8 weeks of life does not exclude Hirschsprung disease].

In a total of 34 children with Hirschsprung's disease, 7 cases showed at first biopsy a normal lamina propria mucosae without aberrant acetylcholine esterase (ACHE)-positive fibres. In further biopsies all 7 cases showed the typical pattern of abundant ACHE-positive nerve fibres in the lamina propria, the last one at the age of 8 weeks. This data suggests that in children with Hirschsprung's disease who have not yet attained their 8th week of life, approximately one-third are without the typical aberrant nerves in the lamina propria. Therefore, we emphasize that a biopsy taken before the 8th week of life showing a negative morphological result should be repeated if the clinical suspicion remains. The late sprouting of the pathological nerves should be considered especially if there are abundant ACHE-positive fibres in the lamina muscularis mucosae.

Acetylcholinesterase↗
PubMed1986

Reuse and reprocessing of disposable medical devices. Legal liability issues.

Reuse and reprocessing of disposable medical devices raises issues of legal liability, especially among physicians, hospitals, and device manufacturers. The practice of reuse has been, at least informally, reported to be fairly widespread. However, the medical risks associated with reuse are unresolved in most cases, which may lead to circumstances conducive to litigation. In this paper, the characteristics of reuse pertaining to legal liability, the parties potentially subject to civil liability suits as a result of reuse, the legal theories underlying claims of injury, and the legal implications of possible policy actions will be examined.

Disposable Equipment↗
PubMed1983

Salivary unconjugated estriol levels in normal third trimester pregnancy - direct correlation with serum levels.

A radioimmunoassay for salivary unconjugated estriol concentration during the third trimester of normal pregnancy is described. The performance characteristics of the method were established by determining the non-specific binding, the blank value of the endogenous estriol free ("stripped") saliva, the recovery experiment and intra- and interassay coefficient of the variations. The corresponding serum samples were also analyzed by the same method. An excellent correlation was found between salivary and serum estriol concentrations.

Estriol↗