The cause of fibrotic diseases, pathologies characterized by excessive production, deposition, and contraction of extracellular matrix, is unknown. To understand the molecular basis of fibrotic disease, it is essential to appreciate how matrix deposition is normally controlled and how this process is dysregulated in fibrogenesis. This review discusses the current state of knowledge concerning interactions among the profibrotic proteins transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF, CCN2), and ED-A fibronectin (ED-A FN) and the antifibrotic proteins tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ).—Leask, A., Abraham, D. J. TGF-β signaling and the fibrotic response.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.03-1273rev

TGF-beta signaling and the fibrotic response.

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Steroidogenesis entails processes by which cholesterol is converted to biologically active steroid hormones. Whereas most endocrine texts discuss adrenal, ovarian, testicular, placental, and other steroidogenic processes in a gland-specific fashion, steroidogenesis is better understood as a single process that is repeated in each gland with cell-type-specific variations on a single theme. Thus, understanding steroidogenesis is rooted in an understanding of the biochemistry of the various steroidogenic enzymes and cofactors and the genes that encode them. The first and rate-limiting step in steroidogenesis is the conversion of cholesterol to pregnenolone by a single enzyme, P450scc (CYP11A1), but this enzymatically complex step is subject to multiple regulatory mechanisms, yielding finely tuned quantitative regulation. Qualitative regulation determining the type of steroid to be produced is mediated by many enzymes and cofactors. Steroidogenic enzymes fall into two groups: cytochrome P450 enzymes and hydroxysteroid dehydrogenases. A cytochrome P450 may be either type 1 (in mitochondria) or type 2 (in endoplasmic reticulum), and a hydroxysteroid dehydrogenase may belong to either the aldo-keto reductase or short-chain dehydrogenase/reductase families. The activities of these enzymes are modulated by posttranslational modifications and by cofactors, especially electron-donating redox partners. The elucidation of the precise roles of these various enzymes and cofactors has been greatly facilitated by identifying the genetic bases of rare disorders of steroidogenesis. Some enzymes not principally involved in steroidogenesis may also catalyze extraglandular steroidogenesis, modulating the phenotype expected to result from some mutations. Understanding steroidogenesis is of fundamental importance to understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiological homeostasis.

The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.

Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

1 Bickel PE, Tansey JT, Welte MA. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochim Biophys Acta 2009; 1791: 419–440. 2 Akimoto N, Sato T, Iwata C et al. Expression of perilipin A on the surface of lipid droplets increases along with the differentiation of hamster sebocytes in vivo and in vitro. J Invest Dermatol 2005; 124: 1127–1133. 3 Tansey JT, Sztalryd C, Gruia-Gray J et al. Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity. Proc Natl Acad Sci USA 2001; 98: 6494–6499. 4 Honma M, Benitah SA, Watt FM. Role of LIM kinases in normal and psoriatic human epidermis. Mol Biol Cell 2006; 17: 1888–1896. 5 Straub BK, Herpel E, Singer S et al. Lipid droplet-associated PAT-proteins show frequent and differential expression in neoplastic steatogenesis. Mod Pathol 2010; 23: 480–492. 6 Wolins NE, Quaynor BK, Skinner JR et al. S3-12, Adipophilin, and TIP47 package lipid in adipocytes. J Biol Chem 2005; 280: 19146–19155. 7 Maekawa M, Ishizaki T, Boku S et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science 1999; 285: 895–898. 8 Watt FM, Frye M, Benitah SA. MYC in mammalian epidermis: how can an oncogene stimulate differentiation? Nat Rev Cancer 2008; 8: 234– 242.

Case of rippled-pattern sebaceoma with clinically yellowish surface and histopathological paucity of lipid-containing neoplastic cells.

Sarcoidosis associated with Basedow's disease.

Lupus alopecia is usually difficult to treat. We report a case of a 40-year-old woman with Sjogren's syndrome and atopic dermatitis who presented with discoid lupus erythematosus on the forearms and lupus erythematosus profundus with alopecia involving the scalp. A biopsy specimen taken from the discoid lupus erythematosus lesion on the forearm further exhibited a xanthomatous reaction, which however was not detected in another specimen from the lupus erythematosus profundus on the scalp. Treatment with oral hydroxychloroquine showed dramatic effects and complete hair regrowth was obtained 3 months later.

Dramatic effect of hydroxychloroquine on lupus alopecia

ejd.2012.1855 Auteur(s) : Takako Miura m-takako@fmu.ac.jp, Toshiyuki Yamamoto Department of Dermatology, Fukushima Medical University, Fukushima 960-1295, Japan A 21-year-old female was admitted to our hospital, complaining of unknown fever, general fatigue, arthralgia, and skin rash. She had intermittent spike fever and cervical lymph node swelling. Physical examination showed urticarial facial erythema on the bilateral cheeks (figure 1A), persistent brownish plaques on the upper back, and linear [...]

Adult-onset Still's disease presenting lupus erythematosus-like facial erythema associated with Kikuchi's disease

Dear Editor, Cutaneous manifestations of dermatomyositis (DM) are various, if rare symptoms are included. We herein describe a rare case presenting with keratotic papules on the buttocks and extremities (Wong-type DM). To our knowledge, this is the first report of Wong-type DM in Japan. A 48-year-old woman was referred to our department, complaining of itchy eruptions on the face, trunk and extremities. She had undergone a surgery for uterine cancer 1 year previously. Physical examination revealed erythemas on the eyelids, forehead and nasolabial areas. Coalescent erythemas were also found on the trunk and extremities. In addition, small, reddish, keratotic papules and papular erythemas were disseminated on the lateral aspects of the thigh, lower back and buttocks (Fig. 1a,b). Laboratory examination showed elevation of aspartate aminotransferase (156 U/L), alanine aminotransferase (57 U/L), lactate dehydrogenase (560 U/L), creatine kinase (6166 IU/L), aldolase (40.2 U/L), myoglobin (103.5 ng/ mL) and erythrocyte sedimentation rate (33 mm/h). Antinuclear antibody and anti-Jo-1 antibody were negative. No interstitial lung disease was detected. Electromyogram of her bicep muscle and the straight muscle of the thigh revealed a myogenic pattern. Magnetic resonance imaging showed high signal intensity in the buttock and thigh muscles. A skin biopsy revealed a keratotic plug with a slight epidermal invagination and dermal perifollicular infiltration of inflammatory cells (Fig. 1c). Results of immunohistochemistry showed CD4and CD8-positive T cells around the follicles (Fig. 1d,e). Another biopsy from the buttocks demonstrated focal lymphocytic infiltration in the subcutaneous tissues. She was successfully treated with systemic prednisolone; however, 8 months later, she died of lymph node metastases and lung metastasis of the uterine cancer. Our patient presented with several types of skin manifestations such as seborrheic dermatitis-like facial erythema, Gottron’s sign, periungual erythema, itchy erythema and panniculitis, as well as generalized follicular keratotic papules on the buttocks and thigh. Histological features of the keratotic papules on the thigh showed follicular hyperkeratosis with mild cellular infiltrates in the upper dermis. Wong-type DM is a rare variant of DM, characterized by keratotic erythematous follicular papules resembling pityriasis rubra pilaris. According to recent review articles, more than 20 cases of Wong-type DM have been reported from countries other than Japan, and to our knowledge, this is the first report from Japan. The involved sites are the trunk and extremities, and several cases include palmoplantar keratoderma. Histological features show follicular hyperkeratosis with keratotic plugs filling dilated follicular infundibula. Our patient had uterine cancer, and developed DM along with the cancer recurrence. The association between Wong-

Toshiyuki Yamamoto

Papers

Case of rippled-pattern sebaceoma with clinically yellowish surface and histopathological paucity of lipid-containing neoplastic cells.

Sarcoidosis associated with Basedow's disease.

Dramatic effect of hydroxychloroquine on lupus alopecia

Adult-onset Still's disease presenting lupus erythematosus-like facial erythema associated with Kikuchi's disease

Wong-type dermatomyositis: A first report from Japan.