Background Hepatocyte nuclear factor 1β (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. Methods We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. Results Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in 6 the patients with heterozygous variants compared to those in patients harboring the deletion (median: 37.6 vs 58.8 ml/min/1.73 m ; p = 0.0091). Conclusion We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.

Objective Our aim was to examine the clinical characteristics and phenotype of lipodystrophy of six diabetic Japanese women with partial lipodystrophy (PL) who received a genetic analysis at a diabetic outpatient clinic. Methods We screened for PL using dual energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) among patients who had a reduced peripheral skinfold thickness at the diabetic outpatient clinic of Kusatsu General Hospital between August 2003 and August 2013. We performed a mutation analysis of candidate genes, including LMNA and PPARG, in two patients with PL and whole-exome sequencing in four patients with PL. Results We identified 15 patients with PL and performed a genetic analysis in 6 of them. They had no mutations in candidate genes known to be associated with familial partial lipodystrophy (FPLD). They all had near-complete loss of subcutaneous fat, particularly in the antero-lateral and posterior thigh region and the calf region. As almost all patients were characterized by fat loss in the lower limbs with abdominal fat accumulation, a high rate of positivity for a family history, diabetes, and an unknown genetic cause, we suspected they might have FPLD1. Some patients have shown relatively severe insulin resistance, while others have shown insulin deficiency. Four and one had severe atherosclerosis and liver cirrhosis, probably due to nonalcoholic steatohepatitis, respectively. Conclusion Almost all patients with PL identified in a diabetic outpatient clinic had subcutaneous fat loss in the lower limbs with excess truncal fat and might have had FPLD1.

We experienced a case of primary intestinal follicular lymphoma and premature atherosclerosis in a diabetic patient with familial partial lipodystrophy (FPL) that was detected when the patient was evaluated for laparoscopic sleeve gastrectomy (LSG). As FPL is generally considered to be rare, FPL is often underdiagnosed, especially in obese patients. Therefore, the prevalence of FPL is higher than previous estimates. Our case illustrates that clinicians should perform screening for atherosclerosis and malignancy at the preoperative evaluation and may need to perform metabolic surgery earlier to prevent the development of excess truncal fat, complicated diabetes and atherosclerosis in patients with FPL.

Expression of human T-cell leukemia virus type-1 (HTLV-1) in adult T-cell leukemia (ATL) cells is known to be marginal in vivo and inducible in short-term culture. In this study, we demonstrated that withdrawal of interleukin (IL)-2 from IL-2-dependent ATL cell lines resulted in induction of HTLV-1 mRNA and protein expression, and that viral induction was associated with phosphorylation of the stress kinase p38 and its downstream CREB. Pharmacological inhibitors of the p38 pathway suppressed viral expression induced by IL-2 depletion. These results indicate that the stress-induced p38 pathway might up-regulate HTLV-1 gene expression through at least CREB activation.

Introduction: Various types of skin lesions with pruritus have been reported in participants of Asian clinical trials on sodium-glucose cotransporter-2 (SGLT2) inhibitors. The aim of this study was to determine whether the diuretic effect of a SGLT2 inhibitor could modify skin hydration status in patients with type 2 diabetes mellitus. Methods: A prospective, short-term, open-label, two-parallel-arm, pilot study was conducted. Eligible patients were assigned to either a SGLT2 inhibitor (50 mg ipragliflozin once daily) group or to a dipeptidyl peptidase-4 inhibitor (50 mg sitagliptin once daily) group (control). The biophysical characteristics of the skin were measured and blood chemistry tests were run in all participants 1 day prior to medication initiation (pre-treatment values) and 14 days thereafter (post-treatment values). Results: Fourteen patients were enrolled in the study, of whom eight were in the ipragliflozin group and six in the sitagliptin group. Compared to the pre-treatment values, the glycated hemoglobin (HbA1c) levels were slightly but significantly reduced in the ipragliflozin group (p = 0.02), but the changes in HbA1c from the pre-treatment to post-treatment time points did not significantly differ between the two treatment groups. Serum 3-hydroxy butyrate levels were significantly higher in the ipragliflozin group than in the sitagliptin group (p \ 0.02). Neither electrical capacitance nor electrical conductance of the stratum corneum (SC), parameters that reflect skin water content, was reduced by 14 days of ipragliflozin treatment; similarly, no changes in these parameters were found in the sitagliptin control group. There was also no difference in the changes in water barrier function of the SC between the two treatment groups. There was a significant linear correlation (p \ 0.01) in skin water content at pre-treatment and that 14 days after treatment with each drug, respectively. Conclusion: Ipragliflozin treatment for 14 days did not significantly affect the skin hydration status in patients with well-controlled type 2