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At least 361 records · Page 20Linked to original sources
PubMed2000

Role of cytotoxic T cells in chronic alopecia areata.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

Alopecia Areata↗
PubMed2002

Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families.

Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron-exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing. We identified 18 mutations, of which 13 were novel and seven (39%) were recurrent. The majority of the mutations were clustered between exons 1-8 and exons 21-26. They comprised four nonsense mutations (22%), eight frameshift insertions or deletions (44%), and six splice-site defects (33%). All mutations predict the formation of premature termination codons. Northern blot analysis showed variable reduction of SPINK5 mutant transcript levels, suggesting variable efficiency of nonsense-mediated mRNA decay. Seven patients were homozygotes, eight were compound heterozygotes, and five were heterozygotes with only one identifiable SPINK5 mutation. Five mutations, one of which resulted in perinatal lethal disease in three families, were associated with certain ethnic groups. We also describe 45 intragenic polymorphisms in the patients studied. The clinical features of erythroderma, trichorrhexis invaginata, and atopic manifestations were present in the majority of affected individuals and ichthyosis linearis circumflexa was seen in 12 out of 24 patients. Interfamilial and intrafamilial variation in disease severity was observed, with no clear correlation between mutations and phenotype, suggesting that the degree of severity may be affected by other factors.

Adolescent↗
PubMed2003

Skin expression of metalloproteinases and tissue inhibitor of metalloproteinases in sibling patients with recessive dystrophic epidermolysis and intrafamilial phenotypic variation.

A number of COL7A1 mutations have now been reported in recessive dystrophic epidermolysis bullosa patients, and the analysis of phenotype-genotype correlations showed evidence for interfamilial and intrafamilial phenotypic variability, occurring for the same mutation. Collagenase and stromelysin activities have been found to be overexpressed in skin cultures of some recessive dystrophic epidermolysis bullosa patients, and tissue destruction in the disease process might result from an imbalance of metalloproteinases (MMP) over tissueinhibitor of metalloproteinases (TIMP). So we suspected that the phenotypic variability for the same mutation could be linked to other genetic or environmental factors, as a particular balance between MMP and TIMP. Organ cultures were performed using explants from the skin of three patients from the same family with recessive dystrophic epidermolysis bullosa to reveal and quantify the expression of MMP-1 (collagenase 1), MMP-2 and MMP-9 (gelatinases A and B), MMP-3 (stromelysin 1), TIMP-1, and TIMP-2, and to compare the results with those obtained with two human control skins, with the same experimental conditions. Increased amounts of all metalloproteinases investigated were observed in the skin of the three recessive dystrophic epidermolysis bullosa affected sibling brothers, both in lesioned and in apparently nonlesioned skin, compared with controls. The amounts of MMP-1, MMP-2, MMP-3, and MMP-9 increased particularly in the skin of the more clinically affected patient. Furthermore for this patient we evidenced higher amounts of MMP-1 and also a lower TIMP-1 amount in his unlesioned and lesioned skin compared with the other two affected patients and with healthy control donors. So we can suspect that recessive dystrophic epidermolysis bullosa phenotypic variability could be related to patients' collagenase activity heterogeneity, linked to imbalance between MMP-1 and TIMP-1.

Adolescent↗
PubMed2006

[Histology of skin and hair follicle].

The skin consists of an outer epidermis, the dermis, and the hypodermis. It includes nerves, blood vessels, glands and hair follicles. Epidermis is a continually renewing, stratified squamous epithelium. It is populated by keratinocytes (80 %) and dendritic cells (20 %) : melanocytes, Langerhans and Merkel cells. In standard histology, keratinocytes are arranged in layers that represent different stages of their differentiation while melanocytes and Langerhans cells appear as clear cells respectively between the basal and the supra-basal cells of epidermis. The Merkel cells cannot be clearly identified. Dendritic processes of the dendritic cells can only be recognized by immunocytochemistry. At the dermal-epidermal junction, a PAS reactive basement membrane follows the contour of the basal cells. Dermis consists of collagenous and elastic fibers embedded into an amorphous ground substance. Fibroblasts, macrophages, mast cells and lymphocytes are its resident cells. Hypodermis is composed of adipocyte lobules defined by fibrous connective tissue septa. Hair follicle consists of 3 parts : the lower portion, from the base of the follicle including hair bulb to the insertion of the arrector pili muscle or buldge ; the isthmus, from the insertion of the arrector pili to the entrance of the sebaceous duct, and the infundibulum, from the entrance of the sebaceous duct to the follicular orifice. The lower portion is composed of the dermal hair papilla, the hair matrix, the hair, and the inner and the outer root sheaths. The hair matrix cells within hair bulb give rise to the hair and to the inner root sheath. With the electron microscope, one can obtain a more detailed view of the characteristic skin structures. Much of them can now be explained in terms of function and in many instances, in correlation with its biochemical composition. An attempt has been made in this paper to precisely give the location of molecules that are relevant in basic skin functions and understanding of auto-immune and genetic diseases.

Adipocytes↗
PubMed1987

[Ascariasis in Western Africa. Epidemiological review].

This paper draws, on the basis of available published reports, an outline of the epidemiological distribution of ascariasis in West Africa. This parasitic disease is easily transmitted in all humid areas which receive more than 1,400 mm rainfall every year. The endemicity pattern is typical of a contamination of the household environment. On the contrary, it is absent, with few exceptions, from a larger part of the region where drier conditions, combined with a series of specific socio-cultural factors, prevent the transmission from being anything else but sporadic. However, the author, although he recognizes that the maintenance of a short living parasite in a population is problematical under sporadic transmission conditions, warns that urban development in the future may very well result in a rapid spread of infections with ascaris.

Africa, Western↗
PubMed1990

[Epidemiology of alveolar echinococcosis in France. 1. Intestinal helminths in the red fox (Vulpes vulpes L.) from Haute-Savoie].

In the course of an epidemiological survey concerning the alveolar echinococcosis and its causative agent, Echinococcus multilocularis, the autopsies of 150 wild red foxes captured in the department of the Haute-Savoie between December 1983 and August 1988 disclosed 139 cases of intestinal helminthiasis with cestodes and nematodes; no trematode was found. Multiple infections were frequent. The cestoda recorded consist of the following species: Taenia crassiceps: 44 cases (29%); Echinococcus multilocularis: 34 cases (23%); Taenia polyacantha: 22 cases (14%); Mesocestoides litteratus: 7 cases (4.6%); Amoebotaenia paradoxa: 1 case (0.6%). The Nematoda concerned are: Uncinaria stenocephala: 79 cases (52%); Toxocara canis: 67 cases (44%); Toxascaris leonina: 16 cases (10%); Trichuris vulpis: 12 cases (8%); Pterygodermatites affinis: 8 cases (5%); Trichostrongyloidea sp.: 5 cases (3%). The animals were not examined for Trichinella spiralis. The results are compared with those observed anteriorly in the province of Auvergne (France).

Animals↗
PubMed2004

Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease.

BACKGROUND AND AIMS: Most human and animal cholestatic disorders are associated with changes in hepatocyte cytoskeleton and tight junctions (TJs). These changes are usually secondary and nonspecific phenomena, both in intra- and extrahepatic cholestasis. Recently, missense mutations in TJ protein 2 (ZO-2) have been identified in patients with familial hypercholanemia. In the liver, TJs separate bile flow from plasma and are composed of strands of claudins and occludin. We previously assigned a syndrome associating ichthyosis and neonatal sclerosing cholangitis (NISCH syndrome) to chromosome 3q27-q28. We considered claudin-1 to be a strong candidate gene based on its mapping to the minimum interval and on the expression pattern of the mouse ortholog. METHODS: The 4 exons and intron-exon junctions of claudin-1 gene were amplified using standard polymerase chain reaction protocols and specific primers. Western blot analysis on cultured fibroblasts and immunohistochemistry on liver tissue section were performed using rabbit anti-claudin-1 antibodies. RESULTS: We described in 4 patients, of 2 inbred kindred of Moroccan origin, a 2-bp deletion (200-201 TT) in exon 1 of the claudin-1 gene arising in a premature stop codon and resulting in total absence of claudin-1 protein in the liver and skin. CONCLUSIONS: Lack of claudin-1 in NISCH syndrome may lead to increased paracellular permeability between epithelial cells. Bile duct injury may be related to the absence of claudin-1 expression in cholangiocytes. Our observation, in conjunction with ZO-2-associated hypercholanemia, emphasizes the role played by TJ components in hereditary cholestasis.

Cholangitis, Sclerosing↗
PubMed2001

The nosology-taxonomy of recent-onset arthritis: the experience of early-arthritis clinics.

OBJECTIVE: To compare the conclusions of studies addressing the outcome of early-arthritis cohorts. METHODS: The methodologies of previous reports on early-arthritis cohorts were examined, and their results and conclusions were compared. RESULTS: Thirty-four reports on 23 cohorts of early arthritis were found. The methodology was poor in most studies, with numerous inclusion and exclusion biases, frequently short follow-up periods, and a lack of precision about the rationale for diagnosis. However, similar conclusions were reached on several points: a large number of cases of early arthritis remained undifferentiated and/or resolved spontaneously, about 80% of cases initially classified as undifferentiated or rheumatoid arthritis retained this diagnosis during follow-up, and the incidence of psoriatic arthritis in most studies was similar (2% to 4%). Conversely, there were striking discrepancies among studies concerning the frequency of crystal arthropathies (0% to 18%), spondyloarthropathy (1% to 33%) and rheumatoid arthritis (15% to 47%). CONCLUSIONS: There appears to be a lack of agreement among researchers about the nosology and/or taxonomy of many cases of mild arthritis, despite the existence of classification criteria. RELEVANCE: Recognition of cultural bias in the diagnosis of early arthritis could be a prerequisite for the optimization of new sets of criteria for the diagnosis of early rheumatoid arthritis and spondyloarthropathy.

Arthritis↗
PubMed2006

Molecular mechanisms underlying the immunomodulatory effects of mistletoe (Viscum album L.) extracts Iscador.

Viscum album (VA) preparations (Iscador) consist of aqueous extracts from different types of European mistletoe. Biologically active components of VA extracts include mistletoe lectins (ML) and viscotoxins. The treatment with VA extracts or with purified ML has been shown to be associated with tumor regression in several in vivo experimental models of tumoral implantation. The mechanisms underlying the anti-tumoral activity of VA or ML are complex and involve apoptosis, angiogenesis and immunomodulation. This review provides an account of the current status of the understanding of the VA-associated immunomodulation in various cell types including lymphoblastoid, monocytic or endothelial cell lines.

Angiogenesis Inhibitors↗
PubMed2004

Chrysopentamine, an antiplasmodial anhydronium base from Strychnos usambarensis leaves.

A new derivative of strychnopentamine was isolated from the leaves of Strychnos usambarensis. This compound, named chrysopentamine, was identified by detailed spectroscopic methods (UV, IR, HR-ESI-MS, 1D and 2D NMR). Chrysopentamine presented an original hydroxy substitution on C-14 and an aromatization of the ring D of strychnopentamine leading to anhydronium base properties and exhibited strong antiplasmodial properties (IC (50) less than 1 microM).

Animals↗
PubMed2006

Esophageal capsule endoscopy versus esophagogastroduodenoscopy for evaluating portal hypertension: a prospective comparative study of performance and tolerance.

BACKGROUND AND STUDY AIMS: Esophagogastroduodenoscopy (EGD) is the most effective method for examining the upper gastrointestinal tract, and particularly for evaluating portal hypertension in cirrhotic patients, especially for screening purposes. The aim of this study was to assess the feasibility, safety, accuracy, and tolerance of PillCam ESO capsule endoscopy for this indication. PATIENTS AND METHODS: In this prospective study, unsedated EGD and capsule endoscopy examinations were conducted on the same day in cirrhotic patients at the time of diagnosis. The patients quantified the tolerability (relative to pain, nausea, choking sensations, etc.) of the two procedures using a 100-mm visual analogue scale. The time required for the recording and for diagnosis with the capsule examination were documented, as were the patients' preferences in comparison with EGD. Two independent endoscopists blinded to the EGD diagnoses assessed the diagnostic accuracy of the images obtained. RESULTS: Twenty-one patients were included in the study (mean age 62, mean Model for End-Stage Liver Disease score 10.5, mean Child-Pugh score 7.3). The procedure was safe. One patient was unable to swallow the capsule. The mean recording time was 213 s (range 6 - 1200 s); the procedure accurately assessed the presence or absence of esophageal varices in 16 of 19 patients (84.2 %); and it correctly indicated a need for primary prophylaxis (esophageal varices of grade 2 or more and/or red signs) in 100 % of cases. The tolerability of the capsule endoscopy examination was significantly better, and all of the patients preferred capsule endoscopy to EGD (which was transnasal in 11 patients). CONCLUSIONS: Capsule endoscopy was feasible, safe, accurate, highly acceptable, and preferred by cirrhotic patients undergoing screening for portal hypertension. This new technique requires further and more extensive evaluation, as well as assessment of its cost-effectiveness.

Aged↗
PubMed1988

[A new early symptom of maculopathy in juvenile diabetes?].

This report presents results of fluorescein angiography performed in 37 patients aged from five to 25 years and treated for diabetes for periods varying from two months to 17 years. Symptoms of microangiopathy were found in eight patients; in 18 others, functional disturbances of the macular pigment epithelium appeared in the form of "window defects." The authors stress the possibility of the occurrence of these initial signs of maculopathy even in the first years following onset of diabetes.

Adolescent↗
PubMed2002

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of patients with atopic dermatitis (AD). OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 1% hydrocortisone acetate ointment in children 2 to 15 years of age with moderate-to-severe AD. METHODS: Treatment was twice daily to affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve (mAUC) as a percentage of baseline. RESULTS: Five hundred sixty patients were randomized and received at least one application of ointment. Discontinuations included 21 of 189 patients from the 0.03% tacrolimus group, 13 of 186 patients from the 0.1% tacrolimus group, and 20 of 185 patients from the hydrocortisone acetate group. The median mEASI mAUC as a percentage of baseline showed 0.03% and 0.1% tacrolimus to be significantly more effective than 1% hydrocortisone acetate (P <.001) and 0.1% tacrolimus to be more effective than 0.03% tacrolimus (P =.006). The mEASI mAUC as a percentage of baseline was 44.8%, 39.8%, and 64.0% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 1% hydrocortisone acetate, respectively. Transient skin burning was the only adverse event to show a higher incidence in the tacrolimus treatment groups than in the hydrocortisone acetate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSION: Tacrolimus, 0.03% and 0.1%, was significantly more effective than 1% hydrocortisone acetate and 0.1% tacrolimus was more effective than 0.03% tacrolimus in the treatment of moderate-to-severe AD in children. No safety concerns were identified.

Administration, Topical↗
PubMed2002

Long-term management of atopic dermatitis in infants with topical pimecrolimus, a nonsteroid anti-inflammatory drug.

BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control. OBJECTIVE: The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months. RESULTS: Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups. CONCLUSIONS: Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Maternal and fetal serum lipid and lipoprotein concentrations and compositions in type 1 diabetic pregnancy: relationship with maternal glycemic control.

The aim of this study was to determine maternal and fetal lipoprotein profiles in type 1 diabetic pregnancies differing in glycemic control. Serum lipid, apolipoprotein, and lipoprotein lipid concentrations were investigated in mothers with poorly controlled or well-controlled type 1 diabetes as reflected by hemoglobin A1c(HbA1c) concentrations performed by isolab column chromatography and in their macrosomic (body wt = 4650 +/- 90 g) or appropriate-for-gestational-age newborns (body wt = 3616 +/- 68 g), and these levels were compared with those in healthy mothers and in their control newborns (body wt = 3290 +/- 45 g). In mothers with well-controlled diabetes and in their infants, serum lipid, apolipoprotein, and lipoprotein lipid concentrations were comparable to those in control mothers and in their control newborns. Mothers with poorly controlled diabetes presented higher serum triglyceride and apoprotein B-100 (apo B-100) levels but lower apo A-I and HDL3 cholesterol and phospholipid levels as compared with control values. In their macrosomic newborns, all serum lipid, apolipoprotein, and lipoprotein lipid levels were higher than those in control newborns. Maternal HbA1c and triglyceride levels in late gestation were significant predictors of fetal lipids and lipoproteins in the poorly controlled diabetes group. In conclusion, when under good metabolic control, type 1 diabetes did not affect maternal and fetal lipid levels. However, when under poor metabolic control, type 1 diabetes is associated with maternal and fetal lipoprotein abnormalities.

Adult↗