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A letter to the editor is presented which discusses the case of a 75-year-old woman with one month history of yellowish rhinorrhoea, nasal stuffiness, and nasal epistaxis who was diagnosed with lipid-rich carcinoma.

Background and Purpose: The connexin (Cx) 32 gene, a member of the gap junction gene family, acts as a tumour suppressor gene in human renal cell carcinoma (RCC) and is down-regulated by the hypermethylation of CpG islands in a promoter region of the Cx gene. The current study investigated whether the restoration of Cx32 silenced by hypermethylation in RCC by a DNA demethylating agent could be an effective treatment against RCC.Experimental Approach: Using nude mice bearing Caki-1 cells (a human metastatic RCC cell line), the effects of 5-aza-2'-deoxycytidine (5-aza-CdR), a DNA demethylase inhibitor, on Cx32 mRNA expression and tumour growth were examined by RT-PCR, and by measuring tumour weight and volume. Cx32 expression in Caki-1 tumours was inhibited by Cx32 short interfering (si) RNA, and the effect of siRNA on 5-aza-CdR-dependent suppression of tumour growth in nude mice was evaluated.Key Results: 5-aza-CdR treatment inhibited the growth of Caki-1 cells in nude mice by 70% and increased 7-fold the level of Cx32 mRNA. The intratumour injection of Cx32 siRNA almost totally inhibited the expression of Cx32 mRNA and significantly reduced the suppression of tumour growth in 5-aza-CdR-treated nude mice.Conclusions and Implications: 5-aza-CdR suppressed the growth of Caki-1 tumours in a xenograft model, by restoring Cx32 expression. This finding suggests that treatment with 5-aza-CdR could be a new effective therapy against human metastatic RCC and that Cx32 could be a potential target for the treatment of RCC. [ABSTRACT FROM AUTHOR]

The Birt-Hogg-Dubé ( BHD) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumours, spontaneous pneumothorax and renal neoplasms with diverse histology. To elucidate its involvement in the development of renal neoplasms, we examined a total of 100 sporadic renal tumours with various histological subtypes for BHD mutation by SSCP-sequencing analyses. We found one germline insertion mutation in the C8 hotspot of exon 11 (c.1733insC), which is known to have a strong association with renal tumour occurrence. The germline-mutated patient suffered from solitary renal cell carcinoma (RCC) but did not have any other BHD manifestations or family history. The tumour revealed heterogeneous cytomorphology, mainly a mixture of eosinophilic and focally clear cells with tubulopapillary architecture. In this tumour, both BHD alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of BHD mRNA detected by real-time quantitative PCR (RQ-PCR) was very low. Renal tumour subtype/nephron segment-specific gene expression detected by RQ-PCR demonstrated that the tumour expressed relatively high amounts of α-methylacyl-CoA racemase ( AMACR) and the KIT oncogene, but relatively low amounts of carbonic anhydrase IX ( CA9), aquaporin 1 ( AQP1), claudin 7 ( CLDN7), parvalbumin ( PVALB), chloride channel Kb ( CLCNKB) and 11-β-hydroxysteroid dehydrogenase 2 ( HSD11B2), suggesting diverse mRNA signatures. Further clustering analysis of 88 renal tumours based on expression of these eight genes sub-classified the tumour as close to oncocytomas and chromophobe RCCs, which are considered distal nephron-associated tumours. These data suggest that somatic mutation of BHD is relatively rare in Japanese patients. The BHD-mutated RCC identified in this study, which exhibits heterogeneous biological features in both morphology and gene expression signatures, seems to deviate from our current understanding of renal tumour classification. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A 22-month-old, male Labrador retriever was presented with anorexia, dyspnoea, and fainting. The dog was diagnosed with a double-chambered right ventricle and tricuspid valve dysplasia using echocardiography and cardiac catheterisation. A marked bilateral pleural effusion was also present and chemical analysis of the fluid confirmed the diagnosis of chylothorax. Using echocardiography, a pressure gradient of 87·1 mmHg was found between the proximal and distal chambers of the double-chambered right ventricle. Initiation of cardiopulmonary bypass allowed the anomalous muscle bundle that divided the right ventricle into two chambers to be resected via a right ventriculotomy. The fainting completely resolved postoperatively, and this treatment seemed quite effective in the reduction of pressure overload ascribable to ejection disturbance. Because the tricuspid dysplasia was not corrected in the first operation, the postoperative chyle effusion was reduced but did not cease. A combination of thoracic duct ligation and passive pleuroperitoneal shunting was effective in the resolution of the chyle effusion. [ABSTRACT FROM AUTHOR]

Background: Fish is one of the most frequent causes of immunoglobulin E (IgE)-mediated food allergy. Although the fish dark muscle is often ingested with the white muscle, no information about its allergenicity and allergens is available. Methods: Heated extracts were prepared from both white and dark muscles of five species of fish and examined for reactivity with IgE in fish-allergic patients by enzyme-linked immunosorbent assay (ELISA) and for allergens by immunoblotting. Cloning of cDNAs encoding parvalbumins was performed by rapid amplification cDNA ends. Parvalbumin contents in both white and dark muscles were determined by ELISA using antiserum against mackerel parvalbumin. Results: Patient sera were less reactive to the heated extract from the dark muscle than to that from the white muscle. A prominent IgE-reactive protein of 12 kDa, which was detected in both white and dark muscles, was identified as parvalbumin. Molecular cloning experiments revealed that the same parvalbumin molecule is contained in both white and dark muscles of either horse mackerel or Pacific mackerel. Parvalbumin contents were four to eight times lower in the dark muscle than in the white muscle. Conclusions: The fish dark muscle is less allergenic than the white muscle, because the same allergen molecule (parvalbumin) is contained at much lower levels in the dark muscle than in the white muscle. Thus, the dark muscle is less implicated in fish allergy than the white muscle. [ABSTRACT FROM AUTHOR]

We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS., (© 2016 Wiley Periodicals, Inc.)

It is already known that some typical dermoscopic patterns seen in melanocytic nevi on the sole have their own favorite site. In the weight-bearing area, melanocytic nevi with a parallel furrow pattern were preferentially observed. Those with a lattice-like pattern were observed in the arch area, whereas those with a crista reticulated pattern were seen in the border area. To investigate the relationship between the distribution of the dermoscopic patterns seen in plantar melanocytic nevi and the 3-D structures of the epidermis, the basal surfaces of the plantar epidermis from 14 skin lesions were observed by scanning electron microscopy (SEM). Our SEM observations revealed that transverse ridges formed a couple of parallel lamellae on the crista profunda limitans (limiting ridges). Between the limiting ridges and the crista profunda intermedia (intermediate ridges), the transverse ridges had different shapes according to the anatomical location of the sole. From these results, it was suggested that the characteristic dermoscopic patterns seen in acquired and junctional melanocytic nevi on the sole simulate the arrangement of transverse ridges., (© 2011 Japanese Dermatological Association.)

Background/aims: Nitric oxide synthase 2 (NOS2) is expressed during liver regeneration after a partial hepatectomy (PHx); NOS2 subsequently synthesizes nitric oxide (NO). However, the role of NOS2-synthesized NO in post-PHx liver regeneration remains unclear. We investigated the role of NOS2-synthesized NO in liver regeneration., Methods: NOS2 knockout (NOS2-KO) mice and control mice were subjected to PHx. Liver mass recovery and serum alanine aminotransferase (ALT) levels were then evaluated. The expressions of Ki-67 and single-strand DNA were also evaluated in remnant liver specimens. Differences in the gene expression profiles of the two groups of remnant liver specimens were analysed using a microarray and were validated using a reverse transcription-polymerase chain reaction (RT-PCR)., Results: In NOS2-KO mice, liver regeneration was delayed and apoptosis and serum ALT levels were higher than the levels in the control mice. A microarray study and RT-PCR revealed that heat shock protein 70 family (HSP70 family), haeme oxygenase 1 (Hmox1), neuropilin 1 (Nrp1) and epidermal growth factor receptor (EGFR) were downregulated in NOS2-KO mice., Conclusions: NOS2-synthesized NO may improve hepatocyte viability through the induction of the HSP70 family and Hmox1 and may sensitize the remnant liver to growth factors through the induction of Nrp1 and EGFR post-PHx.

What Is Already Known About This Subject: Relationships between smell sensation and autonomic changes have been studied extensively. However, the possibility that odorants may also act on the lung and lower airway remains unknown., What This Study Adds: The present results provide the first evidence that the lung and lower airway exert an inhibitory influence on the cardiovascular system in response to Cedrol (odorant) in the air under physiological conditions., Aims: Previous studies reported that Cedrol (odorant) inhalation (CI) induced changes in autonomic balance and baroreceptor sensitivity (BRS) in both healthy subjects and anosmic patients. This suggests that Cedrol may act on the lower airway, and that the pulmonary system may exert an inhibitory influence on the cardiovascular system., Method: To test the above possibility, vaporized Cedrol (64.0 +/- 7.7 10(-9)m) or blank air was directly inhaled through the lower airway from a hole in the trachea, but not through the upper airway, using totally laryngectomized subjects. During the experiment, ECG, systolic (SBP) and diastolic (DBP) blood pressures were measured. Sympathetic and parasympathetic nervous activity was estimated by spectral analyses of variability in these parameters (heart rate variability (HRV), SBP variability (SBPV) and DBP variability (DBPV)). BRS was computed from transfer gain between SBP and the R-R interval of the ECG., Results: SBP and DBP significantly decreased during CI, although there were no significant differences in HR and respiratory rate. BRS significantly increased during CI. The low frequency components of SBPV and DBPV (indices for sympathetic activity) significantly decreased during CI, while high frequency components of HRV (an index for parasympathetic activity) significantly increased., Conclusions: The present experiment using totally laryngectomized patients replicated the similar results in healthy subjects who inhaled Cedrol through the nose, suppression of sympathetic outflow and increase in parasympathetic outflow. These results demonstrated that Cedrol acts on the lower airway and pulmonary system, and suggest a new target for drug therapy of hypertension.