Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

Association between speed of sound of calcaneal bone assessed by quantitative ultrasound and sarcopenia in a general older adult population: A cross-sectional study

BackgroundLower calcaneal speed of sound may be related to sarcopenia because sarcopenia and osteopenia/osteoporosis show a linked relationship in older adults. The purpose of this study is to clarify whether the speed of sound of calcaneal bone assessed by quantitative ultrasound is associated with sarcopenia in a community-dwelling older adult population.MethodsThis was a cross-sectional observational study. The participants in the study were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. The inclusion criteria for participation in the study were (1) aged older than 40 years, (2) living independently, and (3) able to walk without assistance. Those who had nursing care insurance were excluded. Four hundred sixty-seven residents (182 men, 285 women) were registered in the study. Demographic information, fall history, muscle mass index, grip strength, and gait speed were assessed. The speed of sound through the calcaneal bone was evaluated using a CM-200 sonometer. The assessment for sarcopenia is based on the recommendations of the Asian Working Group for Sarcopenia.ResultsSpeed of sound was positively correlated with muscle mass index and gait speed in men, and was positively correlated with grip strength and gait speed in women, when adjusted for age and body mass index. In a multivariate logistic regression analysis adjusted for age and sex and other confounders, speed of sound was independently related with lower gait speed and sarcopenia in women. Speed of sound under 1470.5 m/sec had discriminated for sarcopenia in females.ConclusionWe propose that the speed of sound of calcaneal bone may be used to screen for sarcopenia in women. Sarcopenia should be considered if the speed of sound value is less than 1470.5 m/s in older women.     

Parenchymal calcification is associated with the neurological prognosis in patients with congenital rubella syndrome

Congenital rubella syndrome (CRS) results from maternal rubella virus infection in early pregnancy. Abnormal neuroimaging findings have been analyzed in a small number of CRS patients in the past; however, their clinical significance has been poorly addressed. Therefore, we have investigated the neuroimaging findings of 31 patients with CRS from previous studies. The most common finding was parenchymal calcification, which was observed in 18 of 31 patients (58.1%). A multivariable logistic regression model showed that it was associated with psychomotor or mental retardation (p = 0.018), suggesting that parenchymal calcification in CRS could be a prognostic factor.     

Real-world efficacy and safety of interleukin-17 inhibitors for psoriasis: A single-center experience

We evaluated the efficacy and safety of interleukin (IL)-17 inhibitors (IL-17i) by analyzing 66 patients with psoriasis treated with secukinumab (n = 25), ixekizumab (n = 17) and brodalumab (n = 24) at Kurume University Hospital between December 2014 and June 2019. The mean Psoriasis Area and Severity Index (PASI) scores at baseline were 12.9, 13.4 and 9.9 in the secukinumab, ixekizumab and brodalumab groups (SECg, IXEg and BROg), respectively. At the 6-month evaluation, the mean PASI scores were 1.7, 1.1 and 0.5 in SECg, IXEg and BROg, respectively. The proportion of patients achieving PASI of 3.0 or less was significantly lower in SECg. Drug survivals showed no significant difference among the groups. Although one patient in IXEg died due to an unknown cause, no serious IL-17i-associated adverse event was observed. This study showed high efficacy and relatively low risk of the treatment with IL-17i.     

Epidermal polymeric immunoglobulin receptors: leads from intraepidermal neutrophilic IgA dermatosis‐type IgA pemphigus

In this study, we attempted to identify unknown autoantigen for intraepidermal neutrophilic IgA dermatosis‐type IgA pemphigus by novel IgA‐specific immunoprecipitation. Mass‐spectrometry study identified polymeric immunoglobulin receptor (PIGR) as the candidate protein, and we confirmed that PIGR expressed in both epidermis and cultured keratinocytes. Eukaryotic recombinant protein of PIGR expressed in COS7 cells was reacted with both patient and normal sera, indicating that PIGR binds physiologically to IgA. To detect antigen‐specific binding by IgA autoantibodies, we performed several experiments using deglycosylated PIGR and F(ab)₂ fragments from patient sera. However, these analyses suggested that patient IgA bound physiologically, but not immunologically, to PIGR. Nevertheless, our study provided two important insights. Newly developed IgA‐immunoprecipitation system should be a useful tool in the future study of identification of antigens for IgA autoantibodies. Detection of epidermal PIGR in this study confirmed previous results and indicated possible immunological role of PIGR in epidermis.     

Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative

The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal regenerative therapy has been demonstrated in recent clinical studies, however, little is known about its molecular mechanism (s). We examined the mitogenic response of cultured periodontal ligament (PDL) cells to EMD and characterized associated changes in proliferation-related intracellular signaling molecules, including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response to EMD was associated with the selective activation of extracellular signal-regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were diminished by pretreatment with suramin, an inhibitor of receptor tyrosine kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was similar to that activated by epidermal growth factor (EGF), although the specific binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant treatment with EMD. These findings suggest that EMD elicits its mitogenic signal through an EMD-specific RTK towards ERK 1/2.     

Biochemical and serological studies on oral ureaplasma

This study was conducted to study chemically and serologically the characteristics of the Ureaplasmas isolated from the human oral cavity. Two hundred and fifty-one healthy and 12 periodontitis subjects were examined for the incidence of the isolation of Ureaplasmas from their oral cavity. A total of twenty-six strains was isolated from the healthy human saliva. But no strains could be isolated from a variety of clinical specimens obtained from the patients. The serological properties of the isolates were tested by the method of metabolism inhibition test (MI test). Seven out of 26 isolates were serologically identical with either one of the ATCC standard strains. However, the serological types of the other strains could not be demonstrated by the MI test. The biological characteristics of 4 isolates and ATCC strains were tested by the usual method. The isolates did not metabolize glucose and arginine, while all strains hydrolyzed urea. On the other hand, none of the isolates lysed skimmed milk and gelatin. The proteolytic activity of the isolates could be demonstrated by using casein and horse serum proteins as substrates. Zymogram patterns from one of the isolates and Streptococcus salivarius were obtained by polyacrylamide gel electrophoresis of the cells lysed with digitonin or cell protein extracts. On the basis of the gel electrophoresis patterns, it is clear that the urease of the Ureaplasma is different from that of the Streptococcus salivarius.