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)

clinicopathological features analogous to cutaneous AL-amyloidoma may be incidentally detected in the lungs of patients with SjS, that is, so-called nodular pulmonary amyloidosis (NPA).6,10 Similarly to cutaneous AL-amyloidoma, NPA is characterized by nodular deposits of AL-amyloid in the connective tissue of the lungs, associated with a sparse lymphoplasmacytic infiltrate with monotypic light chain restriction in plasma cell population10; additional points of analogy between NPA and cutaneous AL-amyloidoma include evidence of monotypic restriction for kappa light chain of immunoglobulins in most NPA cases, as well as the fact that occasional patients with NPA may also develop extranodal MZL, including pcMZL.2,6,10 NPA may be thus regarded as the pulmonary counterpart of cutaneous AL-amyloidoma.10 Importantly, NPA is currently considered as a localized low-grade B-cell neoplasm, bearing a close relationship with lymphoplasmacytic neoplasms in the spectrum of MALT lymphomas.10 In conclusion, we believe that the remarkable association between SjS, a chronic autoimmune disease characterized by a well-known risk of development of nodal and extranodal MZL, and cutaneous AL-amyloidoma, as exemplified by our case, further supports the concept that AL-amyloidoma of the skin should be regarded as a peculiar clinicopathological variant of pcMZL.1

IgA Vasculitis After Initiation of Ivermectin for Scabies: Coincident or Drug-Induced?

Plaque psoriasis in a patient with sarcoidosis

Acral lichen myxedematosus showing acro-osteolysis in a patient with Sjögren syndrome.

Dear Editor, Secondary calcification in eccrine poroma is rarely observed, and ossification has yet to be reported. In the present report, we describe a case of eccrine poroma on the chest, with concurrent histological calcification and metaplastic ossification. A 66-year-old man visited our hospital complaining of an asymptomatic nodule on the chest which had appeared 20 years previously. He had experienced occasional bleeding for a few years before presentation. Physical examination revealed a well-circumscribed reddish nodule on the chest with an erosive surface covered with necrotic tissues (Fig. 1a). The nodule was completely removed under local anesthesia. Histological features showed cords of tumor cells extending from the erosive epidermis into the mid-dermis (Fig. 1b). The tumor cells had basophilic cells with small, round nuclei. Of note, lamellar bony structures containing osteoblasts were found beneath the tumor islands (Fig. 1c). Further, calcification was observed within the tumor islands (Fig. 1d). Von Kossa staining revealed ossification and calcification. To date, secondary ossification has been reported in association with various benign as well as malignant tumors, such as melanocytic nevus (nevus of Nanta), blue nevus, organoid nevus, acne, mixed tumor, epidermal and dermoid cysts, trichoepithelioma, pilomatricoma, lipoma, dermatofibroma, keratoacanthoma, pyogenic granuloma, basal cell carcinoma, squamous cell carcinoma and melanoma. To the best of our knowledge, this is the first case of eccrine poroma with metaplastic ossification. Secondary ossification has been observed within the facial lesions in most of the cases. By contrast, eccrine poroma arose on the chest. Osteoblasts play a central role in bone formation, and secrete several inducing factors such as bone morphogenetic protein (BMP)-2, BMP-4, b-catenin, osteopontin, osteonectin and osteocalcin, which exert effects on precursor cells derived from mesenchymal or adipose-derived cells. BMP are members of transforming growth factor (TGF)-b, and transform fibroblasts, primitive mesenchymal cells or progenitor cells in the bone marrow into osteoblasts. In particular, BMP-2 has intense osteoinduction activity, and promotes the differentiation of immature undifferentiated mesenchymal cells into osteoblasts. TGF-b and connective tissue growth factor, which is regulated by TGF-b, may stimulate primitive mesenchymal cells or displaced embryonic cells in the stroma to differentiate into osteocytes.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1346-8138.13473

Eccrine poroma with calcification and metaplastic ossification

巨大尖圭コンジローマはBuschke-Lowenstein腫瘍とも呼ばれ, 主に外陰部で外方に向かって増殖し, 巨大化するHuman papilloma virus (HPV) 感染症に由来する腫瘍性病変である。外観は悪性を思わせるものの, 組織学的には良性の所見をとることが特徴とされる。転移することはないが, 局所での浸潤が深部におよび致命的になることも少なくないため, 治療は根治的切除が一般的である。今回我々は肛門周囲に出現した巨大尖圭コンジローマに対し焼灼術を施行し, 良好な結果を得たので報告する。

https://www.jstage.jst.go.jp/article/skincancer1986/23/1/23_1_80/_pdf

Toshiyuki Yamamoto

Papers

IgA Vasculitis After Initiation of Ivermectin for Scabies: Coincident or Drug-Induced?

Plaque psoriasis in a patient with sarcoidosis

Acral lichen myxedematosus showing acro-osteolysis in a patient with Sjögren syndrome.

Eccrine poroma with calcification and metaplastic ossification

A case of perianal giant condyloma acuminatum