[Evaluation of potentially influential factors for positron emission tomography image quality in liver signal-to-noise ratio utilizing a delivery ¹8F-fluoro-2-deoxy-D-glucose study on Bi4Ge3O12-positron emission tomography/computed tomography].

UNLABELLED: The purpose of this study was to evaluate the relationship of body habitus, blood glucose level and injected dose, respectively, with BGO (Bi4Ge3O12) positron emission tomography (PET) image quality using commercially available 2-deoxy-2-[¹8F] fluoro-D-glucose (FDG). We also evaluated the relationship between PET image quality and acquisition time for each weight group. METHOD: One hundred twenty-five patients (66 male, 59 female) were enrolled in the study. We adopted liver signal-to-noise ratio (liver SNR) as an image quality index, derived from the region of interest (ROI) placed on the axial image of the liver. RESULTS: The correlation coefficient between liver SNR and dose per weight was 0.502. The liver SNR indicated a negative relationship with body weight, body mass index (BMI) and cross sectional area of the patient's body, with the correlation coefficients of -0.594, -0.479 and -0.522, respectively. For all weight groups, an extended acquisition time of at least 60 s/bed was necessary to improve liver SNR. CONCLUSION: The findings of this study are potentially of use for designing imaging protocols for the BGO-PET/CT system when using commercially available FDG. It is easy to obtain good image quality for patients of low to average body size with the standard injection dose. However, large patients should be injected, wherever possible, with an FDG dose of up to 5 MBq/kg. The acquisition time in overweight and obese patients should be as longer as possible than in standard weight patients.

Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation.

We investigated whether or not the topographic regulation of melanocyte differentiation is determined by mesenchymal-epithelial interactions via fibroblast-derived factors. The melanocyte density in palmoplantar human skin (i.e., skin on the palms and the soles) is five times lower than that found in nonpalmoplantar sites. Palmoplantar fibroblasts significantly suppressed the growth and pigmentation of melanocytes compared with nonpalmoplantar fibroblasts. Using cDNA microarray analysis, fibroblasts derived from palmoplantar skin expressed high levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling pathway), whereas nonpalmoplantar fibroblasts expressed higher levels of DKK3. Transfection studies revealed that DKK1 decreased melanocyte function, probably through beta-catenin-mediated regulation of microphthalmia-associated transcription factor activity, which in turn modulates the growth and differentiation of melanocytes. Thus, our results provide a basis to explain why skin on the palms and the soles is generally hypopigmented compared with other areas of the body, and might explain why melanocytes stop migrating in the palmoplantar area during human embryogenesis.

Fixed eruption due to quinine: report of two cases.

Fixed eruption is a characteristic condition with recurrent an erythematous macule in the same location. Because fixed eruption is caused by medical drugs in the majority of cases, it is not so difficult to identify suspicious material by interview. However, it may be difficult in cases in which food additives are responsible. We report two rare cases of fixed eruption due to quinine contained in tonic water. In case 1, a 37-year-old man had repeated erythema on the same sites after drinking a variety of cocktails. We suspected tonic water as the causative material. Oral challenge test of tonic water was positive and patch test with quinine sulfate was positive also. In case 2, a 24-year-old woman in had noticed that her eruption appeared after drinking liquor, especially cocktails as in case 1. She was also positive upon an oral challenge test of tonic water and in a patch test of quinine sulfate.

[Case of urticaria due to cochineal dye in red-colored diet].

We herein describe a 33-year-old female who recurrently exhibited urticaria accompanied by vomiting, diarrhea and dyspnea after taking red-colored food. From her history, we suspected the cochineal dye, the commonly used natural red dye in red-colored food and beverage, to be the cause of her symptoms. Oral provocation test using cochineal dye-stained red-colored boiled-fish-paste induced urticaria and respiratory symptoms. Furthermore the prick tests and the scratch tests with cochineal dye and carminic acid, the major ingredient of cochineal dye, were also positive. These results indicate that type 1 allergy to cochineal dye caused urticaria in this patient. Thereafter, she avoided the foods containing a cochineal dye and showed a complete clinical remission. Recently, the number of literatures described about increased incidence of type 1 allergy to cochineal dye. As the usage of cochineal dye is increasing in the Japanese market, we should keep in mind that cochineal dye can be a cause of urticaria in daily practice.

[Diagnostic criteria of male osteoporosis].

With coming of aged society, male patients with osteoporosis are increasing, and it is important to prevent and treat them. In male osteoporosis, secondary osteoporosis is relatively common as an etiology, and therefore it is necessary to exclude secondary causes, when it will be diagnosed. In female a rapid decrease of bone mineral density (BMD) is observed after menopause, while in male such changes are not. Japanese Society of Bone and Mineral Research proposed diagnostic criteria of male osteoporosis, which 70% of young adult mean (YAM) of hip BMD was used as cut-off value for osteoporosis.

[DXA, QUS, and radiogram].

In this article, an outline of dual energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS), and radiogram, and their characteristics, problems, and assessment of osteoporosis in the elderly were reviewed. It is well known that both DXA and QUS are available to risk assessment of fractures. However, because lumbar bone mineral density (BMD) is overestimated in the elderly complicated with fracture, deformity, and osteosclerotic change in the lumbar vertebra (e), some cases are unsuitable to measurement of BMD with lumbar DXA. To define vertebral fracture, visual semiquantitative and morphometric methods are used. In addition, differential diagnosis of osteoporotic vertebral fractures is necessary. Thus, to establish an exact diagnosis of osteoporosis in the elderly, it is important to understand some problems associated with the elderly.

Mesenchymal-epithelial interactions in the skin: aiming for site-specific tissue regeneration.

Since trunk skin (or non-palmoplantar skin) is less durable under mechanical stress than sole skin (palm, plantar or palmoplantar skin), conventional trunk-derived skin grafts (including the trunk dermis) commonly result in erosion and ulceration when transplanted on to plantar wounds caused by various injuries including, diabetes mellitus or collagen diseases (including systemic sclerosis, polyarthritis nodosa and rheumatoid arthritis). However, trunk-derived epidermis can adopt a plantar phenotype, characterized by keratin 9 expression, hypopigmentation and thick suprabasal layers, through factors derived from plantar dermal fibroblasts in the wounds. Thus, intractable plantar wounds with exposed bones can be treated with the combination of bone marrow exposure, occlusive dressing and epidermal grafting. The higher expression of dickkopf 1 (DKK1), an inhibitor of canonical Wnt/beta-catenin signals, in the plantar dermis partly explains these phenomena. Thus, mesenchymal-epithelial interactions play important roles not only in embryogenesis (the embryonic development) but also in maintaining the homeostasis of adult tissue. The topographical (site-specific) interactions of growth factors and substances, including DKKs, fibroblast growth factors (FGFs) and transforming growth factor-beta (TGF-beta) family proteins including bone morphogenetic proteins (BMPs), may explain the site-specific differences in the skin in addition to the expression patterns of HOX genes and sonic hedgehogs (Shhs). We review the importance of dermal-epidermal interactions in tissue homeostasis and regeneration, especially in palms and soles.

Androgen-inducible TGF-beta1 from balding dermal papilla cells inhibits epithelial cell growth: a clue to understand paradoxical effects of androgen on human hair growth.

We attempted establishing an in vitro coculture system by using human dermal papilla cells (DPCs) from androgenetic alopecia (AGA) and keratinocytes (KCs) to explore the role of androgens in hair growth regulation. Androgen showed no significant effect on the growth of KCs when they were cocultured with DPCs from AGA. Because the expressions of mRNA of androgen receptor (AR) decreased during subcultivation of DPCs in vitro, we transiently transfected the AR expression vector into the DPCs and cocultured them with KCs. In this modified coculture, androgen significantly suppressed the growth of KCs by approximately 50%, indicating that overexpression of AR can restore the responsiveness of the DPCs to androgen in vivo. We found that androgen stimulated the expression of TGF-beta1 mRNA in the cocultured DPCs. ELISA assays demonstrated that androgen treatment increased the secretion of both total and active TGF-beta1 in the conditioned medium. Moreover, the neutralizing anti-TGF-beta1 antibody reversed the androgen-elicited growth inhibition of KCs in a dose-dependent manner. These findings suggest that androgen-inducible TGF-beta1 derived from DPCs of AGA is involved in epithelial cell growth suppression in our coculture system, providing the clue to understand the paradoxical effects of androgens for human hair growth.

In vivo cooperation between Bcl-xL and the phosphoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis.

To investigate the function of Bcl-xL in the skin, we established keratinocyte-specific Bcl-x gene-targeted mice under the keratin 5 promoter (K5). K5.Bcl-xL-/- mice were viable, devoid of alteration in the development of skin or appendages. However, they harbored spontaneous apoptotic keratinocytes in the epidermis. Bcl-xL-deficient keratinocytes cultured in vitro readily underwent apoptosis in the absence of growth factors, but the addition of HGF or EGF resulted in restoration of cell survival, which was reversed by treatment with wortmannin, an inhibitor of phosphoinositide-3 kinase (PI3K). Topical treatment of K5.Bcl-xL-/- mice with wortmannin sensitized the skin for apoptosis induced by UV (UV) B, although wild-type epidermis was only marginally affected by this treatment, suggesting that the resistance to UVB largely depended on PI3K-Akt signaling in Bcl-xL-deficient mice but not in wild-type mice. Furthermore, UVB irradiation resulted in redistribution of phosphorylated Akt from the basal layer to the suprabasal layer, indicating that Akt could spatially cooperate with Bcl-xL upon UVB exposure in the upper epidermis where Bcl-xL is normally localized. These results suggest that Bcl-xL and the PI3K-Akt pathway form a cooperative, intercompensatory axis for the protection of epidermal keratinocytes from apoptosis in vivo.

Neutralization of hepatocyte growth factor leads to retarded cutaneous wound healing associated with decreased neovascularization and granulation tissue formation.

To elucidate biologic functions of hepatocyte growth factor and the c-Met receptor in cutaneous wound healing, we analyzed expression and localization of hepatocyte growth factor and c-Met receptor and used a strategy to neutralize endogenous hepatocyte growth factor in a cutaneous wound healing model in mice. Following excision of full-thickness skin on the dorsum of mice, expression of both hepatocyte growth factor and the c-Met receptor increased transiently in cutaneous tissues. Expressions of hepatocyte growth factor increased as early as 2 d postwounding and reached a peak on day 2, whereas the c-Met receptor expression reached a peak 2-4 d postwounding. Immunolocalization of the c-Met receptor indicated that c-Met receptor expression was upregulated in keratinocytes, vascular endothelial cells, and myofibroblasts in granulation tissue, hence these are potential target cells of hepatocyte growth factor. When normal rabbit IgG or neutralizing anti-hepatocyte growth factor IgG was locally and continuously delivered to subcutaneous lesions, the number of capillary vessels decreased with the neutralization of hepatocyte growth factor and there was an associated decreased expansion of granulation tissue. Likewise, retardation in re-epithelialization and the rate of wound closure occurred with neutralization of endogenous hepatocyte growth factor on days 4 and 7 postwounding. Therefore, hepatocyte growth factor is definitely involved in enhancing cutaneous wound healing processes, including re-epithelialization, neovascularization, and granulation tissue formation.

Rapid compensation for glycosylphosphatidylinositol anchor deficient keratinocytes after birth: visualization of glycosylphosphatidylinositol-anchored proteins in situ.

Pig-a, an X-linked gene, is a key component of glycosylphosphatidylinositol (GPI) anchor biosynthesis based on the fact that lack of this gene causes deficiencies of hundreds of GPI-anchored proteins. We previously demonstrated an essential role for the GPI-anchor in keratinocyte differentiation using male Pig-a knockout mice (K5-Cre:Pig-a flox). Here we analyzed keratinocytes of the female K5-Cre: Pig-a flox/+ mice with heterozygous knockout of Pig-a. These cells exhibited the mosaic pattern of GPI-anchor positive and negative expression typical of random inactivation of the X chromosome. The female K5-Cre:Pig-a flox/+ mice appeared slightly wrinkled with dry skin at birth and white scales starting from 4 d after birth without any histologic abnormality. This phenotype was temporary and milder than that seen in the male knockout mice. To characterize the fate of GPI-anchor-positive cells more clearly, we introduced a transgenic mouse line that expresses enhanced green fluorescent protein in GPI-anchored form into female K5-Cre:Pig-a flox/+ mice and monitored GPI-anchor-positive keratinocytes in situ. Within 36 h after birth, the upper layer of the GPI-anchor-negative zone in epidermis was replaced by the GPI-anchor-positive counterpart. This tissue replacement was accompanied by recovery in trans-epidermal water loss over a similar time course. These observations suggest that the GPI-anchoring is associated with the barrier function as well as with organized differentiation of the epidermis after birth.

Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia.

The gene encoding a transmembrane glycoprotein LIG-1, of which the extracellular region was organized with the leucine-rich repeats and immunoglobulin-like domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed a skin change on the tail and facial area after birth. The affected skin was histologically reminiscent of the epidermis in human common skin disease 'psoriasis'. LIG-1 was expressed in basal cells of the epidermis and outer root sheath cells of hair follicles in mice. Interestingly, the LIG-1 expression was apparently down-regulated in the psoriatic lesions, suggesting that LIG-1 inversely correlates with proliferative ability of epidermal keratinocytes.

Evaluation of provocation test monitoring palmoplantar temperature with the use of thermography for diagnosis of focal tonsillar infection in palmoplantar pustulosis.

BACKGROUND: Since focal tonsillar infections are often associated with palmoplantar pustulosis (PPP), provocation tests have been performed for preoperative evaluation of tonsillectomy. However, these tests have not been fully established. OBJECTIVES: To introduce a more sensitive operative indication for tonsillectomy to the patients with PPP, we have monitored the temperature after provocation tests at palmoplantar sites, as measured by thermography, and we hypothesized that this methodology may lead to a more sensitive marker for tonsillectomy. METHODS: Twenty-two PPP patients with/without clinical tonsillitis were included in this study. After mechanical tonsillar massage, using infrared thermography, we have monitored the surface temperature at palmoplantar sites of 22 patients with PPP, five chronic tonsillitis patients without PPP, and four healthy controls, to compare the findings with the skin lesional outcome after tonsillectomy. RESULTS: There was a significant relationship between the effects of tonsillectomy and the results of provocation tests assessed by thermography. The sensitivity, specificity, and efficiency of the provocation tests with thermography of detecting a favorable outcome of tonsillectomy were 75.0, 83.3, and 77.3%, respectively, while those of the provocation tests as estimated with the conventional criteria were 37.5, 83.3, and 50.0%, respectively. CONCLUSION: Our results suggest that a new indicator using non-invasive thermography for the provocation tests is useful in predicting the effects of tonsillectomy for PPP.

CD4+ T-lymphocyte-induced Epstein-Barr virus reactivation in a patient with severe hypersensitivity to mosquito bites and Epstein-Barr virus-infected NK cell lymphocytosis.

BACKGROUND: Natural killer (NK) cell lymphocytosis associated with Epstein-Barr virus (EBV) infection often shows severe hypersensitivity to mosquito bites (HMB) characterized by intense local skin reactions and systemic symptoms such as high fever, lymphadenopathy, and hepatosplenomegaly. However, the induction mechanism of HMB is still unclear. OBSERVATIONS: We investigated a typical case of HMB with EBV-positive NK cell lymphocytosis. CD4+ T cells dominantly infiltrated the site of the mosquito bite, while EBV-positive cells were few in comparison. CD4+ T cells, but not CD8+ T cells or NK cells, responded to the mosquito salivary gland extracts. Interestingly, coculturing of the NK cells and CD4+ T cells activated by mosquito extracts induced expression of EBV lytic-cycle proteins in the NK cells. Furthermore, the expression of BZLF1, a viral lytic-cycle transactivator, was detectable at the skin lesion induced by scratch patch testing with mosquito extract. The EBV DNA copy number levels in the plasma were elevated in systemic HMB symptoms compared with the normal condition. CONCLUSIONS: CD4+ T cells are important for the primary skin reaction to mosquito bites and might play a key role in reactivation of latent EBV infection in NK cells. This viral reactivation contributed to the pathogenesis of the infectious mononucleosis-like systemic symptoms of HMB in our present case.

Vitamin D and the skin.

Vitamin D was originally discovered as a factor that regulates calcium and bone metabolism. Recent advances in investigation have shown that vitamin D also functions as a regulator of cellular growth and differentiation in various tissues. The skin is not an exception from such effects of vitamin D; it is regarded as a site of its activation and action. Evidence has accumulated showing that the active form of vitamin D and its analogs suppress growth and stimulate the terminal differentiation of keratinocytes. In psoriatic lesions, epidermal keratinocytes exhibit hyper-proliferation and impaired differentiation triggered by inflammation. Therefore, it is quite reasonable that vitamin D is effective on psoriasis. Indeed, within the past decade, analogs of vitamin D3 have been used as topical therapy for psoriasis. In this review, we summarize the fundamental features of vitamin D and the development of vitamin D therapy for psoriasis. Clinical application to other skin diseases and the future of vitamin D therapy in dermatology are also discussed.

Aneurysmal fibrous histiocytoma showing transition from factor XIIIa-positive to -negative.

A 39-year-old woman visited us because of a subcutaneous induration on her forehead of 7 months' duration. The tumor was tender, firm, and colored blue-black. Microscopically, the tumor was composed of fibroblastic and histiocytic cells showing no atypicality. In some part intra- or extracellular haemosiderin was diffusely seen. There were some blood-filled spaces of varying size without endothelial lining. From these findings, this case was diagnosed as aneurysmal fibrous histiocytoma (AFH), a variant form of dermatofibroma. Immunohistochemical analysis showed that factor XIIIa-positive histiocytic cells were distributed in the area without haemosiderin, but such cells were absent in the area with its deposition. Furthermore, the cells near the blood-filled space showed transition from factor XIIIa-positive to -negative, suggesting that the stromal instability induced by the attenuation of factor XIII may lead the formation of the blood-filled spaces in AFH.

Melkersson-Rosenthal syndrome caused by saprodontia: a case report.

A 24-year-old female patient with Melkersson-Rosenthal syndrome (MRS) in association with saprodontia is reported. She presented with lower labial swelling and left facial edema. Histological examination of the involved oral mucosa showed a noncaseating epithelioid granuloma. Results from the laboratory and imaging examinations were normal or negative. Her orofacial swelling disappeared after treatment of the saprodontia of the left first molar.

English version of the interim report published in 1998 by the members of the Advisory Committee on Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.

The Japanese Dermatological Association established an advisory committee in 1995 to set up severity scoring systems for atopic dermatitis (AD). Its interim report was published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998) by Chairman Hikotaro Yoshida. Because of the strong demand for an English version, we have decided to publish the report in English. This prospective study was designed to evaluate the status of 259 AD patients using Method 1, which involves a simple global evaluation of disease severity; Method 2, which involves global evaluation by summing severity scores obtained from five body regions (i.e. the head and neck, anterior and posterior trunks, and upper and lower limbs); Method 3, which consists of both assessment of the extent of involved areas at each of the five body regions and that of the severity scores of each eruption component observed in the most severely affected body region; and Method 4, which consists of the evaluation of only subjective components (daytime pruritus and sleep disturbance). Employing the results obtained with Method 1 as a tentative benchmark, we analyzed its correlation with those of Methods 2, 3 and 4 to statistically assess the validity and reliability of these methods. Method 2, Method 3 and the portion of Method 4 involving evaluation of only the subjective symptom of daytime pruritus but not the sleep disturbance were considered useful in evaluating AD severity.