Crossed Total Hemiatrophy Associated with Atrophoderma of Pasini-Pierini.

A 45-year-old Chinese man had begun to show asymmetry of the face 30 years previously. Subsequently, he developed visual extinction of the right eye, slight numbness, and weakness of the left extremities. Simultaneously, multiple atrophic brownish patches occurred on his side. He denied prior trauma or tick bites at those sites. There was no report of preceding redness, induration, or a history of trauma. The atrophic lesions extended and enlarged slowly. Ten years previously, some brownish patches with normal texture had appeared on the right side of the trunk. There was no further progression of the lesions. In November 2010, the patient consulted our department for the final diagnosis and prognosis of his disease. He did not suffer from epileptic seizures and had no history of a tick bite or Lyme disease.

Centrally located acquired bilateral nevus of ota-like macules: a bizarre pattern.

A 22-year-old woman was referred to our hospital for pigmented lesions located on her face. These had gradually increased during the past 4 years. Computed tomography (CT) of her head revealed no significant parenchymal abnormalities of temporal, maxillary and sphenoid bones or of either parietal bone. Further screening, including neurologic, ophthalmologic, orthopedic, and visceral investigations, did not reveal any abnormalities. There was no family history of abnormal cutaneous pigmentation.

Stem cell factor combined with matrix proteins regulates the attachment and migration of melanocyte precursors of human hair follicles in vitro.

In conjunction with matrix proteins, stem cell factor (SCF) plays an important role in the migration of melanocyte precursors (MPs) derived from the mouse embryo. However, no studies have demonstrated an effect of SCF on human follicular MPs migration in vitro. In this report, first we demonstrate the immature state of the follicular MPs. Then cell attachment rate was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Standard 48-well chemotaxis chambers were used for a transfilter migration assay. F-actin was labeled by rhodamine-conjugated phalloidin, and then organization of the actin cytoskeleton was observed by confocal microscope. In the results, we directly show that MPs adhere more strongly to fibronectin (FN), laminin (LN) and type IV collagen (CIV) than to the negative control. SCF decreased the adhesion of MPs to FN and CIV. A chemotaxis analysis showed that FN and CIV have chemotactic effects on MPs. FN showed an obvious increase in chemotactic effects on MPs with SCF treatment comparing with the control group, but there were no significant changes in the levels of chemotaxis with CIV and LN when the cells were treated with SCF. SCF was chemotactic to MPs, and the presence of FN caused a statistically significant increase in MPs migration at various concentrations of SCF. Furthermore, we showed that SCF, in combination with FN, could induce an apparent increase in actin stress fiber formation in MPs. Our results indicate that SCF, in combination with matrix proteins and in particular with FN, regulates the movement of MPs by both altering cell attachment and increasing cell chemotaxis.

Pentachrome vitiligo in a segmental pattern.

We describe a 22-year-old male with a pigmentary disorder that first appeared when he was 5 years of age. Examination revealed that these lesions were distributed in a segmental pattern on the left side of his trunk. Five shades of colors--white, tan, medium brown, dark brown, and black--were present. The patient told us there had been no preceding inflammation in the affected areas. A biopsy specimen from the inguinal region showed a complete absence of melanocytes, whereas most of the hyperpigmented areas were characterized by increased amounts of epidermal pigment and numbers of melanocytes. Based on the clinical appearance, pentachrome vitiligo in a segmental type was diagnosed.

Three paraneoplastic signs in the same patient with gastric adenocarcinoma.

This is the report of a 76-year-old male with typical lesions of acanthosis nigricans maligna (ANM), florid cutaneous papillomatosis (FCP), and tripe palms (TP) for 2 years. He did not have any gastrointestinal complaints. Pathologic findings of skin supported the diagnosis of ANM. Because gastric adenocarcinoma is the most common neoplasm associated with these paraneoplastic dermatoses, further tests were carried out. Endoscopic examination was performed and an adenocarcinoma of the esophagogastric junction was confirmed. Meanwhile, multiple small polyps in the middle and the lower thirds of the esophagus were observed. The patient was referred for further evaluation and subsequent surgical resection of the tumor.Acanthosis nigricans (AN) is a hyperkeratotic mucocutaneous eruption of heterogenous etiology, which is characterized by hyperpigmentation, velvety cutaneous thickening, intensified skin markings, and development of verrucous excrescences typically involving the intertriginous areas. AN is classified into benign and malignant forms on the basis of clinical associations. Malignant acanthosis nigricans (MAN) tends to be extensive and involves mucosal surfaces, mostly in elderly people. Florid cutaneous papillomatosis (FCP), also known as the Schwartz-Burgess syndrome, is characterized by the rapid appearance of multiple verrucous lesions that are clinically indistinguishable from common warts [1]. Tripe palms (TP) is characterized by diffuse, yellowish palmar hyperkeratosis, with enhancement of the epidermal ridges on the hands (dermatoglyphics), resembling intestinal villosities [1]. The association of these three paraneoplastic dermatoses (FCP, ANM and TP) in the same patient has been reported. Herein, we report an elderly male with three paraneoplastic dermatoses for two years. On the initial presentation, he did not report any systemic complaints; diagnostic tests confirmed the presence of a gastric adenocarcinoma.

Bilateral milia en plaque in a 6-year-old Chinese boy.

Milia en plaque is a rare variant of miliathat occurs spontaneously on an erythematous base without identifiable causative factors. Approximately 40 cases have been recorded in the literature. Most occurred in the periauricular area, affected middle-aged patients, and showed a predilection for women. Here, we report a case of milia en plaque on the bilateral posterior helices in a 6-year-old Chinese boy.

Combining fermentation to produce O-succinyl-l-homoserine and enzyme catalysis for the synthesis of l-methionine in one pot.

The biosynthetic pathway of l-methionine in microorganisms was complex and regulated at multiple levels. In this study, a two-step method for l-methionine production combined fermentation and biocatalysis was realized in one pot. The O-succinyl-l-homoserine (OSH) producing strain Escherichia coli W3110(DE3) ΔIJB∗TrcmetL/pTrc-metAfbr-Trc-thrAfbr-yjeH (ΔIJB) was constructed initially. OSH in the fermentation supernatant was then converted to l-methionine in the presence of O-succinyl-l-homoserine sulfhydrylase (OSHS) and sodium methanethiol. The titer of l-methionine could reach 21.1 g/L after 88 h (84 h fermentation and 4 h catalysis) in a two-step method (process 1). In a one-pot two-strain system (process 2), two strains ΔIJB and E. coli BL21(DE3)/pET28b-OSHS-cutinase were co-cultured, and 8.24 g/L l-methionine was obtained. In another one-pot one-strain system (process 3), strain E. coli ΔIJB/pET28b-OSHS-cutinase could co-express OSHS and cutinase during ΔIJB fermentation at the same time, obtaining 13.6 g/L l-methionine in a 5 L fermentor after 84 h. By comparing the three processes for l-methionine production based on the process 1, the simplified process in process 3 provided in this study showed potent in the large-scale production of l-methionine with convenient handling and production efficiency, but further works still need to be carried out to improve the l-methionine production.

Identification and Characterization of an O-Succinyl-L-Homoserine Sulfhydrylase From Thioalkalivibrio sulfidiphilus.

L-methionine is an important natural amino acid with broad application prospects. A novel gene encoding the enzyme with the ability to catalyze O-succinyl-L-homoserine (OSH) to L-methionine was screened and characterized. The recombinant O-succinyl-L-homoserine sulfhydrylase from Thioalkalivibrio sulfidiphilus (tsOSHS) exhibited maximum activity at 35°C and pH 6.5. OSHS displayed an excellent thermostability with a half-life of 21.72 h at 30°C. Furthermore, the activity of OSHS increased 115% after Fe2+ added. L-methionine was obtained with a total yield reaching 42.63 g/L under the concentration of O-succinyl-L-homoserine 400 mM (87.6 g/L). These results indicated that OSHS is a potential candidate for applying in the large-scale bioproduction of L-methionine.

O-Succinyl-l-homoserine overproduction with enhancement of the precursor succinyl-CoA supply by engineered Escherichia coli.

O-Succinyl-l-homoserine (OSH) is an important platform chemical in production of C4 chemicals such as succinic acid, homoserine lactone, γ­butyrolactone, and 1,4­butanediol. The production of OSH through chemical method or the current engineering strain is difficult and not optimal, and thereby there remains a need to develop new engineering strategy. Here, we engineered an OSH overproducing Escherichia coli strain through deleting the degradation and competitive pathways, overexpressing thrA and metL to enhance the metabolic flux from l-asparate to l-homoserine. Additionally, increasing the precursor succinyl-CoA supply through simultaneously knocking out sucD and overexpressing sucA further increased the yield of OSH. The engineered strain OSH9/pTrc-metA11-yjeH with above strategies produced OSH at the concentration of 24.1 g/L (0.609 g/g glucose) in batch fermentation. To gain detailed insight into metabolism of the engineered strain, comparative metabolic profiling was performed between the engineered and wide-type strain. The metabolomics data deciphered that the carbon was directed toward the OSH biosynthesis resulting in less flexibility of the genetically modified strain than the wide-type strain.

Blaschkoid pityriasis versicolor.

A 31-year-old male patient complained of having follicular and brownish red maculopapules along the Blaschko's lines on the right chest for 2 days. On examination, follicular brownish maculopapules were present on the chest with a uniform size of about 3 mm in diameter. The lesions were isolated without a tendency to merge, giving several S-shaped, band-like appearances. Direct mycological examination of the skin flakes revealed many pseudomycelial hyphae and yeast cells with typical spaghetti and meatball appearance. Wood's light examination of the lesion revealed a golden yellow fluorescence. A diagnosis of blaschkoid pityriasis versicolor was suggested because of blaschkoid distribution of the lesions in this new variant of PV.

Annular fixed drug eruption.

Fixed drug eruption (FDE) usually presents as a single oval to round violaceous patch after administration of the causative drug. We describe a case of FDE presenting with multiple annular erythematous lesions over dorsal aspects of both feet following the administration of phenobarbital. To the best of our knowledge, such an atypical demonstration had never been reported. Fixed drug eruption should be considered in the differential diagnosis of annular lesions.

The distribution of melanocytes and the degradation of melanosomes in fetal hair follicles.

There have been many studies about the formation, storage, transport and degradation of melanosomes in epidermal melanocytes but studies of melanocytes and melanosomes in fetal hair follicles (HFs) have been limited and ambiguous. The goal of this study was to investigate the distribution of melanocytes and the degradation of melanosomes in fetal HFs. After obtaining approval and informed consent for the study, a scalp specimen from a 5 month gestational age fetus was obtained and was divided into two parts. One part was subjected to immunohistochemical staining with the melanocyte-specific marker HMB-45 and was then observed by light microscopy to detect the distribution of melanocytes in HFs. The other part underwent conventional processing for transmission electron microcopy (TEM). Subsequently, the morphology of melanosomes in HF melanocytes and their degradation in cortical keratinocytes were observed. Immunohistochemically, scattered round melanocytes lacking dendrites were mainly observed along the outer root sheath of the lower part of the HF. A few fusiform or tri-dendritic melanocytes were located at the bottom of the hair bulbs. Significantly melanized melanocytes with multiple dendrites were concentrated in the pigmented area in the center of the hair bulbs, only above the dermal papilla. Analysis by TEM revealed melanocytes containing melanosomes at all stages of development. Autophagosomes containing stage mature IV melanosomes were observed in some melanocytes. Many phagolysosomes containing numerous melanosomes were observed in the cortical keratinocytes. Some phagolysosomes were concentrically surrounded by 3-5 layers of endoplasmic reticulum. Melanosomes that had been degraded or were being degraded in phagolysosomes in keratinocytes had lost their integrity and had become an ill-defined melanosomal dust that were arranged irregularly. Partial melanin particles were released into the cytosol. Melanocytes in different regions of fetal HFs had different morphologies and were at various stages of differentiation. Fetal HF melanocytes contained not only melanosomes at different developmental stages, but autophagosomes were seen occasionally. Melanosomes were degraded into irregular pigment particles in the phagolysosomes of cortical keratinocytes. These results provide important clues to elucidate the mechanism of melanosome biodegradation.

Linear and whorled nevoid hypermelanosis complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris.

We report a 17-year-old girl who presented with linear and whorled melanosis following Blaschko lines mainly on her trunk. Ichthyosiform lesions and linear scaling erythemas were observed respectively on her lower limbs and the dorsa of her hands, left knee, ankle and foot. No abnormality was found in systemic examination and blood tests. A biopsy specimen of pigmentation of her back showed there was increased pigmentation within the basal keratinocytes, with focal incontinentia pigmenti. Notable lymphangiectasis could also be seen in the mid part of dermis, which had never previously been described. The biopsy of scaling erythemas of her hand showed dominant hyperkeratosis with focal parakeratosis, acanthosis and papillomatous hyperplasia in the epidermis. The diagnosis of linear and whorled nevoid hypermelanosis (LWNH) complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris was made in accordance with clinical and pathological manifestations. LWNH ought to be differentiated from incontinentia pigmenti and hypomelanosis of Ito.

[Advancements in melanocytes in hair follicle].

Melanoblasts, the precursors to melanocytes, originate in the neural crest. Some melanoblasts can travel to the hair follicle and further differentiate into pigment melanin-producing melanocytes. Hair follicles contain a pool of undifferentiated melanocyte stem cells (MSCs), which are sources of differentiated melanocytes, and functional melanocytes exhist in the hair bulb. The volume, life, and activity of melanocytes in a hair follicle is closely related with the growth cycle of follicle. Appearance of gray hair gray results from incomplete MSCs maintenance.

A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3.

Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted and reticulate pigmentation of the flexures. The gene, or even the chromosomal location, for RPAF has not yet been identified. In this study, one Chinese family with RPAF was identified and subjected to a genomewide screen for linkage analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination fraction theta=0.00). Haplotype analyses indicated that the disease gene is located within the 6.8 cM region distal to D17S1798. It is the first locus identified for RPAF. This study provides a map location for isolation of a disease gene causing RPAF.

A modified method for purifying amelanotic melanocytes from human hair follicles.

We describe a modified method for establishing long-term pure cultures of amelanotic melanocytes (AMMC) derived from human hair follicles. Normal human corpse scalp (just after death, 1 h) was transected 1 mm below the epidermis, and hair follicles in the remaining dermis were isolated by a two-step enzyme treatment. Hair follicle cell suspensions were prepared by 0.50% trypsin treatment for 30 min and cultured in an optimized melanoblast proliferation nature mitogen medium. Cells attached to the substratum were mostly amelanotic melanocytic in character with small, bipolar shapes in the early stage; only a few keratinocytes and rare fibroblasts were observed. Keratinocytes were easily removed by differential trypsinization. After the third passage, the proliferating cells were all amelanotic melanocytes as confirmed by immunostaining with polyclonal antibodies to alphaPEP7h, which recognized the tyrosinase protein located on melanosomes and NKI/beteb, which is a pre-melanosomal antigen against synthetic peptides corresponding to the carboxyl termini of human melanosomal protein GP100. Cultured AMMC were highly positive to L-dopa reactivity after the addition of IBMX to the culture medium for 7 days. Many stage I and II melanosomes and occasional stage III melanosomes without stage IV melanosomes were found in the cytoplasm by transmission electron microscope. This modified technique is potentially more suitable for cultivating amelanotic melanocytes. The availability of pure cultures of hair-follicle amelanotic melanocytes will facilitate investigations of the roles of those cells in migration and differentiation during treatment of vitiligo.