Birt‐Hogg‐Dubé syndrome‐associated renal cell carcinoma: Histopathological features and diagnostic conundrum

Birt‐Hogg‐Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome‐associated RCC (BHD‐RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD‐RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD‐RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD‐RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD‐RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD‐RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD‐RCC from other hereditary RCC are also briefly discussed.     

Atopic dermatitis without serum immunoglobulin E elevation or loss-of-function filaggrin gene mutation in a patient with X-linked agammaglobulinemia

A case of atopic dermatitis (AD) with X-linked agammaglobulinemia (XLA), which is one of the primary immunodeficiency diseases, is reported. A 12-year-old boy had suffered from dry skin and recurrent itchy eruptions since he was 2 years old, and he was diagnosed as having XLA at the age of 4 years. His total immunoglobulin (Ig)E level was 7 IU/mL, even with regular Ig replacement therapy. Furthermore, filaggrin (FLG) mutations known in the Japanese population were not found. His skin lesions were well controlled by the application of a mild-class topical steroid and a moisturizer, though he developed folliculitis due to Staphylococcus aureus infection during treatment with a strong-class topical steroid. This case suggests that the FLG mutation and IgE-mediated sensitization are not necessary to induce AD skin manifestation.     

Fate of full‐house immunofluorescence staining in renal allograft: A case report

Here, we report the case of a patient with renal allograft with full‐house immunofluorescence staining in the zero‐hour biopsy. Full‐house immunofluorescence staining is a well‐known characteristic of lupus nephritis. Previous studies have reported patients with full‐house immunofluorescence staining, but without other symptoms or serological findings; this condition is referred to as full‐house nephropathy. We identified only one case out of 2203 zero‐hour biopsies over 13 years. Zero‐hour biopsy presented no glomerular changes but showed full‐house immunofluorescence staining. Electron microscopy revealed a nonorganized electron‐dense deposit mainly in the mesangial lesion. Systemic lupus erythematosus (SLE)‐associated antibodies were negative, and complement deficiency was not observed in the donor patients. Deposition of immunoglobulin and complement levels markedly decreased within 1–3 years post transplantation. Neither donor nor recipient developed clinical or biological features of SLE; they showed good renal prognosis.     

Aspects of interleukin-8 gene expression by gingival and dermal fibroblasts stimulated with interleukin-1beta or tumour necrosis factor alpha

Fibroblast-derived interleukin (IL)-8 is thought to have an important role in the orchestration of immuno-participant cells infiltrating the skin and gingiva in response to continuously recurring bacterial infection. Therefore, the IL-8 gene expression should be under tight regulatory control and it might be temporally and spatially limited in inflammatory tissue. The purpose of this study was to examine the aspect of the IL-8 gene expression by fibroblasts stimulated with pro-inflammatory cytokines, IL-1beta and TNF-alpha. In situ hybridisation revealed that fibroblasts did not express IL-8 mRNA whereas keratinocytes and endothelial cells did in IL-1beta- or TNF-alpha-injected mice skin. However, cultured mouse dermal fibroblasts expressed not only IL-8 but also IL-1beta mRNA without stimulation by exogenous IL-1beta and TNF-alpha, and the expression was not enhanced by the exogenous cytokines. A similar result was obtained in late-passage human gingival fibroblasts. These results suggest that fibroblasts remain insensitive to IL-1beta and TNF-alpha so as to induce the IL-8 gene expression in non-inflammatory mice skin. Mouse dermal and late-passage human gingival fibroblasts in vitro are likely to be altered in phenotype into IL-8-producing cells along with the production of IL-1beta. In skin inflammation and periodontal diseases, fibroblasts may express the IL-8 gene even without an exogenous cytokine, IL-1beta or TNF-alpha, during their proliferation similar to the situation in our culture system.     

Assessment of in vitro interleukin-2-producing capacity of peripheral blood lymphocytes from patients with periodontitis.

Abstract In this cross-sectional study, we assessed the in vitro interleukin-2 (IL-2) producing capacity of peripheral blood mononuclear cells (PBMC) and lymphocytes from patients with different forms of periodontitis. 45 patients (12 with localised early onset periodontitis (LEOP), 20 with generalised early onset periodontitis (GEOP), and 13 with adult periodontitis (AP), and 20 periodontally healthy subjects (HS), participated in this study. PBMC and lymphocytes were isolated from the subjects and their cells were stimulated with an anti-CD3 monoclonal antibody (anti-CD3 MoAb) and the secreted IL-2 levels in the culture were bioassayed. No significant differences could be found in IL-2 producing activity of PBMC between the patients and HS group. There was wide interindividual variation and high and low “IL-2 producers” were noted. We found a LEOP patient who was a high producer of IL-2 (>mean+8 SD) and 2 LEOP patients and a HS who were low producers of IL-2 (相似文献   

Effect of xylitol gum on the level of oral mutans streptococci of preschoolers: block-randomised trial

Objectives: To assess the influence of xylitol chewing gum consumption on mutans streptococci level of 3–4 years old Japanese preschoolers. Methods: 248 participants were examined regarding caries‐related factors at baseline and were followed up at 6, 9, and 12 months after the baseline: assessors were blinded, subjects were open labelled and blocked parallel randomised; 142 were selected to use xylitol gum for 3 months (from months 6 to 9) and 106 were controls. Results: 161 participants were analysed (xylitol n = 76, control n = 85). Nineteen caries‐related variables, including xylitol gum consumption, were analysed for any association with the main outcome, plaque mutans streptococci scores development within the intervention period, by logistic regression. Six showed statistically significant associations by univariate analysis (P < 0.05). However, only xylitol gum consumption remained a significant negative association (P < 0.05) by multiple analyses. Interestingly, over 10% xylitol group children experienced diarrhoea, which was larger than previous investigations. Conclusion: Xylitol gum is effective in avoiding increased plaque mutans streptococci in young children.     

Regional brain imaging of vesicular acetylcholine transporter using o‐[125I]iodo‐trans‐decalinvesamicol as a new potential imaging probe

In this study, the regional rat brain distribution of radioiodinated o‐iodo‐trans‐decalinvesamicol ([¹²⁵I]OIDV) was determined in vivo to evaluate its potential as a single‐photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [¹²⁵I]OIDV passed freely across the blood–brain barrier and accumulated in rat brain. The accumulation of [¹²⁵I]OIDV in rat brain was significantly reduced by coadministration of (+/?)‐vesamicol (0.125 µmol). In contrast, the coadministration of σ‐receptor ligands, such as (+)‐pentazocine (0.125 µmol) as a σ‐1 receptor ligand and (+)?3‐(3‐hydroxyphenyl)‐N‐propylpiperidine (0.125 µmol) as a σ‐1 and σ‐2 receptor ligands, barely affected the accumulation of [¹²⁵I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations. Synapse 68:107–113, 2014. © 2013 Wiley Periodicals, Inc.