Gene–gene interactions in IL23/Th17 pathway contribute to psoriasis susceptibility in Chinese Han population

Background Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. Objective To investigate the gene–gene interactions in IL23/Th17 pathway underlying psoriasis. Methods A total of 299 single‐nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene–gene interactions. Results We found that there were a three‐way interaction among IL21, CCR4 and TNF(χ² = 5.02(1), P = 0.025) and three pair‐wise gene–gene interactions between IL12RB1 and CCR4(χ² = 11.66(4), P = 0.0201), IL22 and CCR4 (χ² = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ² = 7.31(1), P = 0.0069) in psoriasis. Conclusions Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis.     

Ichthyosis associated with widespread tinea corporis: report of three cases

Ichthyoses are a common group of keratinization disorders. A non-inflammatorygeneralized persistent skin desquamation is observed. It is characterized byincreased cell turnover, thickening of the stratum corneum and functional changes ofsebaceous and sweat glands. All of these favor fungal proliferation. Dermatophytesmay infect skin, hair and nails causing ringworm or tinea. They have the ability toobtain nutrients from keratinized material. One of its most prevalent genera isTrichophyton rubrum. Although tineas and ichthyoses are quite common, the associationof the two entities is rarely reported in the literature. Three cases of ichthyosisassociated with widespread infection by T. rubrum are presented. Resistance toseveral antifungal treatments was responsible for worsening of ichthyosis signs andsymptoms.     

Dermoscopic features of thin melanomas: a comparative study of melanoma in situ and invasive melanomas smaller than or equal to 1mm

BACKGROUND

Dermoscopy allows the early detection of melanomas. The preoperative determination of Breslow index by dermoscopy could be useful in planning the surgical approach and in selecting patients for sentinel lymph node biopsy.

OBJECTIVES

This study aims at describing the dermoscopic features of thin melanomas and comparing melanomas in situ with invasive melanomas less than or equal to 1 mm thick.

METHODS

This was an observational retrospective study in which the dermoscopy photographs of 41 thin melanomas were evaluated. Three observers evaluated together 14 dermoscopic criteria.

RESULTS

Among thin melanomas, the most frequent criteria were presence of asymmetry in two axes in 95% of cases (39 cases), 3 or more colors in 80.4% of cases (33 cases), atypical dots or globules in 58.5% of cases (24 cases) and atypical network or streaks in 53.6% of cases (22 cases). The group of invasive melanomas presented with a higher frequency and statistical significance (p <0.05) 3 or more colors (OR: 16.1), milky red areas (OR: 4.8) and blue-white veil (OR: 20.4), and a greater tendency to have streaks or atypical network (OR: 3.66).

CONCLUSIONS

Thin melanomas tend to have asymmetry in the two axes, 3 or more colors, atypical dots or globules and atypical network or streaks. Melanomas in situ tend to have up to 2 colors, no blue-white veil and no milky red area. Invasive melanomas tend to have 3 or more colors, a milky red area, blue-white veil, and atypical network or streaks. Further studies are needed to confirm these findings.     

The synergistic effect of low-dose cyclosporine and fluocinolone acetonide on the survival of rat allogenic skin graft

Either cyclosporine (CsA) or fluocinolone acetonide (FA) may prolong the survival of skin allografts. This study was performed to evaluate the effect of combination of these two treatments. BUF rat skin was transplanted to LEW rat. The mean survival time (MST) of control grafts was 9.9 days. In rats fed low dose CsA (2.5 or 5mg/kg/day, blood CsA 221 or 631 micrograms/ml), the MST were 16.0 days. When FA with or without CsA topically applied only, their MST were 22.7 or 24.1 days. If topical application of CsA + FA in combination with low dose oral CsA, the grafts survived indefinitely when the treatment was continued (100 days). The synergistic effect of CsA and topical FA is significant and provides a potential safe means for prolonging skin allograft survival following burn injury.     

Microencapsulated parathyroid cells as a bioartificial parathyroid. In vivo studies

Parathyroid cells were isolated from healthy rats, encapsulated in alginate-polylysine membranes, and injected intraperitoneally into rats on which total parathyroidectomies had been performed. Three days posttransplant, serum calcium and PTH-M concentrations had increased to near-normal levels in the recipient animals. Similar results were observed in a separate group of parathyroidectomized rats 3 days after free parathyroid cells were implanted, but within 4 weeks serum calcium and PTH-M concentrations had decreased almost to pretransplant levels in these rats. In the rats with encapsulated cell transplants, by contrast, serum calcium and PTH-M levels were significantly higher, even after 8 weeks. No therapeutic effects were observed in rats injected with empty capsules or in the control group, which received no capsules or cells. These results indicate that transplants of microencapsulated parathyroid cells can temporarily reverse aparathyroidism in rats without the use of immunosuppressive drugs, and that further studies are warranted to investigate possible future clinical applications of this treatment.     

Ultrasound-guided percutaneous needle biopsy in diseases of the chest

This paper presents the results of ultrasonically guided percutaneous fine needle biopsy in 85 cases with suspected space-occupying lesions of the lung, pleura and mediastinum. The results was positive in 97.6% (83/85), and the accurate diagnostic rate 98.8% (82/83). The incidence of pneumothorax was only 2.4%. The authors believe that this method has the advantages of being simple and easy in operation with high diagnostic rate and few complications.     

Evaluation of the human choroidal melanoma rabbit model for studying microcirculation patterns with confocal ICG and histology.

The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A human choroidal melanoma cell line (OCM1) was implanted in the choroid of 40 rabbit eyes using three different techniques: transscleral choroidal injection of a cell suspension, injection of a cell suspension in a surgically induced cyclodialysis cleft, and implantation of solid tumor fragments in a surgically induced cyclodialysis cleft. The rabbits were immunosuppressed with daily injections of Cyclosporin A to prevent host versus graft reaction. The eyes were studied weekly with indirect ophthalmoscopy and fundus photography to monitor tumor growth and indocyanine green angiography using a confocal scanning laser ophthalmoscope to identify microcirculation patterns in vivo and correlate these findings with the histologic demonstration of tumor microcirculation patterns. A tumor mass was identified by indirect ophthalmoscopy in 16 of the 40 implanted rabbit eyes (40%). Each of these tumors was confirmed histologically to represent a focal elevated choroidal mass. All 16 elevated choroidal masses grow in eyes in which solid tumor fragments were implanted. In total, a melanoma was identified histologically in 28 of the implanted 40 eyes (70%). In addition to the 16 eyes where the melanoma appeared as a focal elevated choroidal mass, 4 eyes contained a focal elevated mass in the sclera and 8 eyes contained a flat choroidal tumor. Histologically, microcirculation patterns were identified only in the 16 eyes with focal elevated choroidal masses. Confocal indocyanine green angiography imaged microcirculation patterns in 13 of these 16 eyes (81%). The surgical implantation of small solid fragments of human choroidal melanoma in immunosuppressed rabbit eyes provides the best method to consistently obtain focal elevated choroidal masses. These focal elevated choroidal masses resemble booth the localization and the growth pattern of choroidal melanomas in humans. In addition, they also contain microcirculation patterns similar to those seen in humans that are detectable with confocal indocyanine green angiography. The use of indocyanine green angiography with this animal model may be especially useful in designing and evaluating anti-microcirculation treatments directed at uveal melanoma.     

Characterization of a mouse Cx50 mutation associated with the No2 mouse cataract.

PURPOSE: Recently, a missense mutation in the mouse connexin 50 (Cx50) gene has been associated with the nuclear opacity 2 (No2) mouse cataract. This missense mutation (D47A) resulted in an aspartate-to-alanine substitution at amino acid position 47 in the first extracellular domain of Cx50. To better understand the role of Cx50 in the pathogenesis of congenital cataract, the functional consequences of the D47A mutation in the Xenopus oocyte expression system were studied. METHODS: D47A was constructed using polymerase chain reaction (PCR) mutagenesis. Xenopus oocytes were injected with in vitro transcribed cRNA encoding wild-type mouse Cx50 (Cx50wt), wild-type rat Cx46 (Cx46wt), D47A, or combinations of wild-type and mutant connexins. The oocytes were then devitellinized and paired. Gap junctional conductance (Gj) was measured using a dual two-microelectrode voltage-clamp technique. RESULTS: Homotypic oocyte pairs expressing wild-type Cx50 or Cx46 were well coupled. In contrast, oocytes injected with D47A cRNA did not form gap junctional channels when paired homotypically. To test whether the D47A mutation could interact with wild-type connexins in a dominant negative manner, oocytes were injected with equal amounts of mutant and wild-type connexin cRNA, mimicking the heterozygous condition. Expression of D47A did not inhibit the development of junctional conductance in paired oocytes induced by wild-type Cx50 or Cx46. CONCLUSIONS: These results indicate that the D47A mutation acts as a loss-of-function mutation without strong dominant inhibition. In No2 mice, the mutation would be predicted to result in a reduction in intercellular communication, leading to cataractogenesis. It may also cause other qualitative changes such as a change in permeability for small molecules.     

Analysis of two types of cone bipolar cells in the retina of a New World monkey, the marmoset, Callithrix jacchus.

Two types of cone bipolar cells, the blue cone bipolar cell and the diffuse bipolar cell (DB3), were labelled immunohistochemically and investigated in the retina of a New World monkey, the marmoset. Blue cone bipolar cells were labelled with an antiserum against cholecystokinin. Short-wavelength-sensitive (SWS) cones were labelled with an antiserum against the SWS cone opsin. The DB3 cells were labelled with antibodies to calbindin. Blue cone bipolar cells in marmoset do not form a regular mosaic but instead follow the random distribution of the SWS cones. Nevertheless, the SWS cone to blue cone bipolar cell connectivity in marmoset is very similar to that previously described for macaque. In contrast to the blue cone bipolar cells, the DB3 cells form a regular mosaic. The synaptic connectivity of DB3 cells in the inner plexiform layer was analyzed. They make output synapses onto ganglion cells and amacrine cells, and gap junctions with each other. Our results provide further evidence for the existence of parallel bipolar cell pathways in the primate retina and support the view that the retinae of Old World and New World primates have common neuronal connectivity. The random distribution of SWS cones and blue cone bipolar cells is an exception to the general rule of a regular mosaic distribution of cell populations in the retina.     

Cytomegalovirus retinitis in HIV-infected patients with and without highly active antiretroviral therapy.

PURPOSE: To assess the impact of highly active antiretroviral therapy on the epidemiology of cytomegalovirus retinitis in patients infected with the human immunodeficiency virus (HIV). METHODS: In a study performed in a single center for infectious diseases, we compared the data collected in 1995 (without highly active antiretroviral therapy) with 1997 data (with highly active antiretroviral therapy). RESULTS: In a comparison of 1997 with 1995 data, the mean CD4+ cell count of patients with cytomegalovirus (CMV) retinitis was higher (169 +/- 150 CD4/microl vs 15 +/- 47 CD4/microl) (P = .05), and the relapses of CMV retinitis were less frequent (17% vs 36%) (P = .02). Newly diagnosed CMV retinitis decreased from 6.1% (59 of 952 patients) in 1995 to 1.2% (nine of 726 patients) in 1997 (P < .0001). In 1997, patients with newly diagnosed or relapsing CMV retinitis had a lower mean CD4+ (37 +/- 42) cell count than patients with no relapsing CMV retinitis (197 +/- 160) (P = .01). CONCLUSION: The incidence and recurrences of CMV retinitis decreased from 1995 to 1997, probably as a result of restored immunity while the patients were undergoing highly active antiretroviral therapy; however, the increasing frequency of HIV resistance to highly active antiretroviral therapy justifies close ocular follow-up.