RESUMEN
The patient is a 47-year-old female. MRI revealed a well-defined submuscular mass in the bladder muscle layer. Bladder paraganglioma was suspected based on MRI findings. Endocrinologic Testing showed no significant elevation. 123I-MIBG scintigraphy of the mass showed a significant uptake, and we made diagnosis of bladder paraganglioma. The mass was nonrising and showed no color differentiation making its location undetectable. Using MRI with a ureteral stent and urethral catheter in place, we were able to determine its location. The possibility of damage to the ureteral or internal urethral opening was feared. We chose open bladder surgery, emphasizing ease of operation and visualization. Although a transient increase in blood pressure was observed during the operation, the mass was resected as a single mass from all layers of the bladder without damaging the ureteral or internal urethral opening. Histopathological examination revealed a paraganglioma.MRI (ureteral stent and urethral catheter placement) and open bladder surgery were useful for identifying the location and resecting this case of this otherwise undetectable bladder paraganglioma.
Asunto(s)
Paraganglioma , Uréter , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Persona de Mediana Edad , Vejiga Urinaria/diagnóstico por imagen , Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/cirugía , Procedimientos Quirúrgicos Urológicos , Paraganglioma/diagnóstico por imagen , Paraganglioma/cirugíaRESUMEN
BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS. METHODS: We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating (n=21, from 14 families) and nontruncating (n=25, from 15 families) mutations at the transcript level. RESULTS: We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns (n=14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations (P=0.001). CONCLUSIONS: We report unpredictable atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations.
Asunto(s)
Colágeno Tipo IV/genética , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad/epidemiología , Nefritis Hereditaria/genética , Mutación Puntual/genética , Adulto , Estudios de Cohortes , Análisis Mutacional de ADN , Humanos , Japón , Masculino , Nefritis Hereditaria/diagnóstico , Nefritis Hereditaria/epidemiología , Linaje , Estudios RetrospectivosRESUMEN
BACKGROUND: The pathogenesis of thiazolidinediones (TZDs)-induced hepatic steatosis in genetically obese diabetic mice has not been fully clarified. We herein examined the effects of pioglitazone treatment on liver histology. METHODS: To investigate TZDs-induced hepatic steatosis, KKAy mice were treated with pioglitazone orally or by intraperitoneal injection. RESULTS: Orally administered pioglitazone at 15 and/or 50 mg/kg/day worsened the hepatic steatosis in KKAy mice, however, the treatment at 50 mg/kg/day was not worse than that at 15 mg/kg/day. The basal expression of peroxisome proliferator-activated receptor (Ppar)γ mRNA in the liver was upregulated to approximately 10% of that in white adipose tissue in these mice. Although no induction of hepatic Pparg mRNA by pioglitazone treatment was observed, the mRNA expression of the downstream lipogenic enzymes significantly increased. On the other hand, intraperitoneal administration of 15 mg/kg/day did not lead to deterioration of the hepatic steatosis of KKAy mice. Moreover, intraperitoneal administration led to an accompanying shift of fat distribution from intra-abdominal to subcutaneous adipose depots, and further increases in the serum adiponectin levels. In addition, a 5 day treatment without any change in body weight led to an obvious improvement in hepatic steatosis. CONCLUSIONS: Intraperitoneal administration of pioglitazone can act more strongly on intra-abdominal adipose tissues, and attenuates TZDs-induced hepatic steatosis in KKAy mice. The present study suggests that hepatic steatosis due to chronic treatment with TZDs is affected by the balance between endogenous lipogenesis in the liver and the lipid storage in adipose tissues, both occurring through PPARγ.
RESUMEN
Sterol regulatory element binding protein (SREBP)-1 is a membrane-bound transcription factor that regulates the expression of several genes involved in cellular fatty acid synthesis in the peripheral tissues, including liver. Although SREBP-1 is expressed in brain, little is known about its function. The aim of the present study was to clarify the characteristics of SREBP-1 mRNA expression in rat brain under various nutritional and hormonal conditions. In genetically obese (fa/fa) Zucker rats, expression of SREBP-1 mRNA was greater in liver than in hypothalamus or cerebrum compared to the lean littermates of these rats. Fasting for 45 h and refeeding for 3 h did not affect expression in brains of Wistar rats of SREBP-1 mRNA or the mRNAs of lipogenic enzymes that are targets of SREBP-1, i.e., fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC). Infusion of 2.0 mIU insulin or 3.0 microg leptin into the third cerebroventricle did not affect SREBP-1 mRNA expression in either hypothalamus or cerebrum. SREBP-1 mRNA expression in brains of transgenic mice that overexpressed leptin did not differ from that of wild-type mice. However, we observed a unique age-related alteration in SREBP-1 mRNA expression in brains of Sprague-Dawley rats. Specifically, SREBP-1 mRNA expression increased between 1 and 20 months of age, while there was no such change in the expression of FAS or ACC. This raises the possibility that increased SREBP-1 expression secondary to aging-related decline of polyunsaturated fatty acid (PUFA) might compensate for the reduction of FAS expression in brain. These findings suggest that the expression of SREBP-1 and downstream lipogenic enzymes in brain is probably not regulated by peripheral nutritional conditions or humoral factors. Aging-related changes in SREBP-1 mRNA expression may be involved in developmental changes in brain lipid metabolism.
Asunto(s)
Envejecimiento/fisiología , Encéfalo/metabolismo , Regulación de la Expresión Génica/fisiología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Acetil-CoA Carboxilasa/administración & dosificación , Factores de Edad , Animales , Northern Blotting/métodos , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Ayuno/fisiología , Ácidos Grasos/administración & dosificación , Expresión Génica/efectos de los fármacos , Expresión Génica/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Insulina/farmacología , Leptina/deficiencia , Leptina/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Ratas Zucker , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
We examined the effects of chronic centrally administered leptin on the glucose metabolism of streptozotocin-induced diabetic (STZ-D) rats, a model for insulin-dependent diabetes mellitus. When 3 microg.rat(-1).day(-1) of leptin was infused into the third ventricle for 6 consecutive days (STZ-LEP), STZ-D rats became completely euglycemic. The effect was not seen when the same dosage was administered s.c. Centrally administered leptin did not affect peripheral insulin levels. The feeding volume of STZ-LEP rats was suppressed to the level of non-STZ-D control rats. No improvement of hyperglycemia was noted when STZ-D rats were pair-fed to match the feeding volume of STZ-LEP rats. Thus, the euglycemia of STZ-LEP rats cannot be due to the decreased feeding volume. In the STZ-D rat, glucokinase mRNA, a marker of glycolysis, is down-regulated whereas glucose-6-phosphatase mRNA, a marker of gluconeogenesis, and glucose transporter (GLUT) 2, which is implicated in the release of glucose from liver, are up-regulated. GLUT4, uncoupling protein (UCP) 1, and UCP3 were down-regulated in brown adipose tissue. These parameters returned to normal upon central infusion of leptin. GLUT4 was not down-regulated in the skeletal muscle of STZ-D rats; however, fatty acid binding protein and carnitine palmitoyltransferase I, markers for utilization and beta-oxidation of fatty acids, were up-regulated and restored when the rats were treated with leptin. The increase and subsequent decrease of fatty acid utilization suggests a decrease of glucose uptake in the skeletal muscle of STZ-D rats, which was restored upon central leptin administration. We conclude that centrally infused leptin does not control serum glucose by regulating feeding volume or elevating peripheral insulin, but by regulating hepatic glucose production, peripheral glucose uptake, and energy expenditure. The present study indicates the possibility of future development of a new class of anti-diabetic agents that act centrally and independent of insulin action.