Glial fibrillary acidic protein mutations in adult‐onset Alexander disease: clinical features observed in 12 Japanese patients

Yoshida T, Sasayama H, Mizuta I, Okamoto Y, Yoshida M, Riku Y, Hayashi Y, Yonezu T, Takata Y, Ohnari K, Okuda S, Aiba I, Nakagawa M. Glial fibrillary acidic protein mutations in adult‐onset Alexander disease: clinical features observed in 12 Japanese patients.
Acta Neurol Scand: 2011: 124: 104–108.
© 2010 John Wiley & Sons A/S. Objective – To clarify the clinical manifestations of adult‐onset Alexander disease (AOAD) in Japanese patients with glial fibrillary acidic protein (GFAP) gene mutations. Methods and materials – Twelve patients of AOAD with GFAP mutations detected in our centre were examined for neurological and magnetic resonance imaging (MRI) findings. Results – Major symptoms were pyramidal and bulbar signs. In addition, three patients presented abnormal behaviour and/or memory disturbance. Two of the three patients also had Parkinsonism and had been diagnosed with fronto‐temporal dementia or progressive supranuclear palsy until GFAP mutations were detected. Abnormalities of the medulla oblongata and cervical spinal cord were observed on MRI in all patients. Conclusions – Patients presenting with pyramidal and/or bulbar signs with abnormalities of the medulla oblongata and cervical spinal cord on MRI should be considered for GFAP analysis as this is the typical presentation of AOAD. Abnormal behaviour and cognitive disorders including deterioration of memory were rare symptoms but could be an obstacle to diagnosing Alexander disease.     

Previous fracture surgery is a major risk factor of infection after total knee arthroplasty

Purpose  

Total knee arthroplasty (TKA) has been proven to be the most effective treatment for patients with severe joint disease. Although infection is not a frequent complication, it is certainly one of the most dreaded. The purpose of this study was to identify factors associated with infection after TKA.     

Statistical analysis of diagnostic failure of fine needle aspiration cytology (FNAC) in breast cancer

Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among those, 57 cases failed in accurate diagnosis of malignancy and 243 were successful. Fourteen clinicopathological factors altogether were analyzed to elucidate any correlation with FNAC failure using uni- and multivariate analysis. The univariate analysis in each clinicopathlogical factor showed that these error cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers, small-sized of tumors, scattered type of cancer cell distribution in tumor tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with benign-like ultrasound findings and with low TNM stage. The multivariate analysis revealed tumor grade was the strongest factor for all, followed by cellular distribution type of cancer cells and benign-like ultrasound findings. From these results, we speculated that diagnostic failure of FNAC at first clinic visit seemed to be caused by mainly two histocytological factors: extrinsic factor (structural factors of tissue-like tumor cells' distribution pattern, etc.); and intrinsic one (cellular factors of low atypism such as benign-like ultrasound finding, low tumor grade, and so on).     

Anin vitro invasion model for human renal cell carcinoma cell lines mimicking their metastatic abilities

We developed a modifiedin vitro invasion assay system using monolayers of vascular endothelial cells. A type I collagen gel was formed in plastic dishes, and overlaid with type IV collagen. Calf pulmonary arterial endothelial (CPAE) cells were seeded onto these plates, and incubated until they reached confluence. Five human renal cell carcinoma cell lines with various metastatic potentialsin vivo were then seeded on the monolayer CPAE cells, and their colony formation and invasion activities were examined for 9 days. At day 4, the highly metastatic cell lines increased the number of colony foci on monolayer CPAE cells several fold higher than their poorly metastatic counterpart. The horizontal spreading patterns were also different between poorly and highly metastatic cell lines. On day 9, the number of carcinoma foci that penetrated the monolayer of CPAE cells and type IV collagen sheets into type I collagen gels in highly metastatic cell lines greatly increased as compared with that of poorly metastatic cell lines. Ourin vitro invasion assay using monolayer CPAE cells would be useful to evaluate protease activities and colony formation during invasion.     

Malignant thymoma associated with liposarcoma of the mediastinum —A case report—

Malignant thymoma occurring concurrently with mediastinal liposarcoma in a 49-year-old man is described. The patient underwent an incomplete resection of the mediastinal mass followed by irradiation therapy and additional chemotherapy. He died about 9 months after the detection of a mediastinal mass on chest X-ray films and the immediate cause of death was superior vena cava syndrome. The incidence of primary liposarcoma of the mediastinum alone is extremely rare. Only a few more than 20 with such a lesion have been docummented in Japan. A review of the literature of patients with mediastinal liposacoma and thymoma associated with malignancies revealed no case of an association of thymoma and liposacoma.     

Endogenous Fructose Production and Fructokinase Activation Mediate Renal Injury in Diabetic Nephropathy

Diabetes is associated with activation of the polyol pathway, in which glucose is converted to sorbitol by aldose reductase. Previous studies focused on the role of sorbitol in mediating diabetic complications. However, in the proximal tubule, sorbitol can be converted to fructose, which is then metabolized largely by fructokinase, also known as ketohexokinase, leading to ATP depletion, proinflammatory cytokine expression, and oxidative stress. We and others recently identified a potential deleterious role of dietary fructose in the generation of tubulointerstitial injury and the acceleration of CKD. In this study, we investigated the potential role of endogenous fructose production, as opposed to dietary fructose, and its metabolism through fructokinase in the development of diabetic nephropathy. Wild-type mice with streptozotocin-induced diabetes developed proteinuria, reduced GFR, and renal glomerular and proximal tubular injury. Increased renal expression of aldose reductase; elevated levels of renal sorbitol, fructose, and uric acid; and low levels of ATP confirmed activation of the fructokinase pathway. Furthermore, renal expression of inflammatory cytokines with macrophage infiltration was prominent. In contrast, diabetic fructokinase–deficient mice demonstrated significantly less proteinuria, renal dysfunction, renal injury, and inflammation. These studies identify fructokinase as a novel mediator of diabetic nephropathy and document a novel role for endogenous fructose production, or fructoneogenesis, in driving renal disease.Diabetic nephropathy is the most common kidney disease causing ESRD worldwide and also one of the most difficult diseases to treat. To date, treatment includes tight blood glucose and BP control and inhibition of the renin-angiotensin-aldosterone system. These efforts typically slow but do not arrest the progression of kidney disease.¹ It is therefore imperative to better understand the mechanisms responsible for renal injury and to develop additional therapies.Recently, fructose has emerged as a potential nephrotoxin. Fructose-fed rats develop modest tubulointerstitial injury,² and fructose supplementation accelerates renal disease in the remnant kidney model.³ While all studies to date have focused on dietary fructose as the source of fructose, fructose can also be generated from glucose in diabetes because of the activation of the polyol pathway in the proximal tubule. To date, no studies have examined the role of this endogenous fructose production or fructoneogenesis in driving diabetic nephropathy. Therefore, we tested the hypothesis that mice lacking fructokinase-ketohexokinase (khk−/−) show protection from diabetic nephropathy, even in the absence of dietary fructose, as a result of their inability to metabolize endogenously produced fructose.     

Impact of sleep-disordered breathing, visceral fat accumulation and adiponectin levels in patients with night-time onset of acute coronary syndrome

Acute coronary syndrome (ACS) during sleep occurs at a relatively low frequency and the pathogenic background remains uncertain. The aim of the present study was to determine the significance of sleep-disordered breathing (SDB) and excess visceral fat with nocturnal dysregulation of adipocytokines in night-time onset of ACS. SDB, visceral fat area (VFA), and changes in circulating adipocytokine levels were assessed in 109 consecutive patients with ACS. SDB and VFA were assessed by cardiorespiratory monitoring and computed tomographic scan, respectively. Visceral fat accumulation was more common in patients with (12 to 7 a.m.) than without (7 to 12 a.m.) night-time onset of ACS (p <0.05). In patients with night-time onset of ACS, those with excess visceral fat were significantly more likely to have SDB and nocturnal dysregulation of adiponectin than those without such accumulation (p <0.05), but there was no difference between those with and without excess visceral fat (VFA cutoff 100 cm(2)) in patients with non-night-time onset of ACS. In conclusion, night-time onset of ACS is associated with excess visceral fat and SDB (referred as to "syndrome Z"). SDB and excess visceral fat are treatable risk factors. Decrease of excess visceral fat and treatment of SDB could be beneficial in in preventing nocturnal cardiac events.     

Association between pre‐pregnancy body mass index and gestational weight gain and perinatal outcomes in pregnant women diagnosed with gestational diabetes mellitus: The Japan Environment and Children's Study

Aims/IntroductionWe investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG).Materials and MethodsData from the national birth cohort in the Japan Environment and Children''s Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM.ResultsThe OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m² and insufficient GWG (<2.75 kg) was 1.78 (1.02–3.12). The OR of having a large for gestational age infant of the same BMI group with excessive GWG (>7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m² in the GDM group than in the non‐GDM group.ConclusionsLarge for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m² are at risk of having small for gestational age and large for gestational age infants depending on GWG.