Clinical and genetic analysis in a family with familial renal glucosuria: Identification of an N101K mutation in the sodium–glucose cotransporter 2 encoded by a solute carrier family 5 member 2 gene

We report the identification of a mutation in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium–glucose cotransporter 2, in a family with familial renal glucosuria. The proband was a 26‐year‐old Japanese man referred to the diabetes division with repeated glucosuria without hyperglycemia. His mother, uncle and grandfather also had a history of glucosuria. A heterozygous missense mutation (c.303T>A:p.N101K) in SLC5A2 was identified in the patient and his mother, but not in 200 chromosomes from 100 healthy and unrelated individuals, or in 3,408 Japanese individuals in the Tohoku Medical Megabank. Furthermore, bioinformatics software predicted that this lesion would be pathogenic. We infer that the mutation led to clinically relevant sodium–glucose cotransporter 2 dysfunction. The patient showed no symptoms of hypoglycemia, but continuous glucose monitoring confirmed asymptomatic hypoglycemia.     

Dynamic intersection of the longitudinal muscle and external anal sphincter in the layered structure of the anal canal posterior wall

Purpose

The minute details of the structure of the anal canal are still not well understood. The complex structural configuration of the muscles, ligaments and raphes remains unclarified. This study was undertaken to determine the precise structure of the posterior part of the anal canal and to facilitate an understanding of previous studies.

Methods

For macroscopic examination, 14 right pelvic halves from 14 Japanese cadavers were used. Observation and dissection were performed from the median plane. In the histological examination, six left pelvic halves were used. The sections of the posterior parts of the anal canal were stained with hematoxylin and eosin, Elastic van Gieson, anti-smooth actin antibody and anti-skeletal myosin antibody.

Results

We identified the following muscles arranged from the internal side to the external side: internal anal sphincter, longitudinal muscle (LM), external anal sphincter (EAS) and levator ani muscle (LAM). Two different types of conformation of the posterior part of the anal canal were found, each bearing a different shape of EAS. In both types, LM penetrated the inferior part of EAS. After penetrating EAS, some fibers of LM ran posterosuperiorly and attached to the “the posterior fibers” which reach the dorsal side of the coccyx.

Conclusions

We defined and labeled the connective tissues between the anal canal and coccyx on the basis of their relative position to LAM. Based on a comparison of the two types of the posterior part of the anal canal, we propose that there are two phases due to constriction and relaxation of LM.     

Notch Signaling May Be Involved in the Abnormal Differentiation of Epidermal Keratinocytes in Psoriasis

Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions.     

Case Report: Adrenal Oncocytoma Associated with Markedly Increased FDG Uptake and Immunohistochemically Positive for GLUT1

Usually, benign tumors are not associated with an increased F-18 fluorodeoxyglucose (F-18 FDG) uptake on positron emission tomography (PET), although some exceptions have been reported in adrenal neoplasms. We present a rare case of adrenocortical oncocytoma associated with markedly increased FDG uptake, demonstrating a maximum standardized uptake value of 46.8. Histological examination demonstrated diffuse proliferation of tumor cells with eosinophilic and granular cytoplasm that were diffusely immunopositive for mitochondria and glucose transport protein 1, with focal and weak immunopositivity for 3β-hydroxysteroid dehydrogenase. Ultrastructural examination also revealed abundant mitochondria in the tumor cells. The tumor was diagnosed as adrenocortical oncocytoma and was considered benign according to Lin-Weiss-Bisceglia criteria. Diagnosis of adrenocortical oncocytoma can pose difficulties during both preoperative radiological and postoperative histopathological investigations.     

Clinical utility of treatment method conversion during single-session endoscopic ultrasound-guided biliary drainage

BACKGROUND Although several techniques for endoscopic ultrasound-guided biliary drainage(EUS-BD)are available at present,an optimal treatment algorithm of EUS-BD has not yet been established.AIM To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD.METHODS This was a single-center retrospective analysis using a prospectively accumulated database.Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included.The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session.Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success,clinical success,and adverse events(AEs).RESULTS A total of 208 patients underwent EUS-BD during the study period.For 18.8%(39/208)of the patients,the treatment methods were converted to another EUSBD technique from the initial plan.Biliary obstruction was caused by pancreatobiliary malignancies,other malignant lesions,biliary stones,and other benign lesions in 22,11,4,and 2 patients,respectively.The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures:Target puncture(n=13),guidewire manipulation(n=18),and puncture tract dilation(n=8).Technical success was achieved in 97.4%(38/39)of the cases and clinical success was achieved in 89.5%of patients(34/38).AEs occurred in 10.3%of patients,including bile leakage(n=2),bleeding(n=1),and cholecystitis(n=1).The puncture target and drainage technique were altered in subsequent EUSBD procedures in 25 and 14 patients,respectively.The final technical success rate with 95%CI for all 208 cases was 97.1%(95%CI:93.8%-98.9%),while that of the initially planned EUS-BD was 78.8%(95%CI:72.6%-84.2%).CONCLUSION Among multi-step procedures in EUS-BD,guidewire manipulation appeared to be the most technically challenging.When initially planned EUS-BD is technically difficult,treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.