Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene

EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1 alpha promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 -- possible heterodimeric partners for EAT in the anti-apoptotic process -- were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.     

Influence of renal function on clinico-pathological features of primary hyperparathyroidism

OBJECTIVE: Disturbed renal function may play an important role in the clinico-pathological presentation of primary hyperparathyroidism (pHPT). We studied the influence of renal function on the clinico-pathological characteristics of 141 patients (123 women and 18 men) with surgically proven pHPT. METHODS: The 141 patients were assigned to one of two groups based on creatinine clearance (C(cr)) level: a renal insufficiency group (n=37) in which C(cr) of patients was <70 ml/min and a normal renal function group (n=104) in which C(cr) was > or =70 ml/min. Clinical presentation and biochemical indices were evaluated and compared between the two groups. RESULTS: Age, and frequency of hypertension and of diabetes mellitus were significantly (P<0.001, P<0.05 and P<0.05 respectively) higher in the renal insufficiency group than in the normal renal function group. Serum levels of calcium, intact parathyroid hormone and bone Gla protein were significantly (P<0.05) higher and the excised parathyroid weighed significantly more (P<0.05) in the renal insufficiency group than in the normal renal function group; however, serum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and 24 h urinary calcium excretion were significantly (P<0.001 and P<0.05 respectively) lower in the former than in the latter group. There was a significant inverse correlation between C(cr) level and serum calcium (r=0.315, P<0.001) and a significant positive correlation between C(cr) level, 1,25(OH)(2)D (r=0.315, P<0.001), and 24 h calcium excretion (r=0.458, P<0.0001). CONCLUSIONS: Clinico-pathological features of pHPT were notably influenced by even moderate renal insufficiency. Urinary calcium excretion decreased according to the decrease in glomerular filtration rate. Therefore, endocrinologists need to appraise urinary calcium excretion and renal function of pHPT patients when considering surgery or in discriminating familial hypocalciuric hypercalcemia.     

Risk factors of renal involvement and significant proteinuria in Henoch-Schönlein purpura

Risk factors of renal involvement and significant proteinuria in patients with Henoch-Sch?nlein purpura (HSP) were retrospectively evaluated by univariate and multivariate analyses. The analysis was performed in 134 patients with HSP. Renal involvement was found in 65 patients (49%) and 97% of the renal involvement was found within 3 months of disease onset. Moderate or severe proteinuria was recognised in 25 patients. A univariate analysis revealed that an age of more than 4 years at the onset, severe abdominal pain with gastrointestinal bleeding, persistent purpura over a month, coagulation factor XIII activity < 80%, and treatment with factor XIII concentrate were associated with developing renal involvement. A multivariate analysis showed that severe abdominal symptoms, an age of more than 4 years, and persistent purpura increased the risk of renal involvement. Risk factors of moderate or severe proteinuria were also examined. The risk factors in a univariate analysis were severe abdominal symptoms, persistent purpura, decreased factor XIII activity, treatment with steroids, and treatment with factor XIII concentrate. Of those, persistent purpura, treatment with factor XIII concentrate, and factor XIII activity < 80% were associated with significant proteinuria in a multivariate analysis. Among the patients with severe abdominal symptoms, factor XIII activity was significantly decreased in patients with significant proteinuria compared to other patients without significant proteinuria. CONCLUSION: Long-term prognosis of Henoch-Sch?nlein purpura is dependent on the severity of renal involvement. In those patients who have the risk factors of renal involvement, especially significant proteinuria, close attention should be paid to a urinalysis for at least 3 months from the onset of the disease.     

Studies of Magnesium in Congenital Long QT Syndrome

We studied the role of magnesium (Mg) in congenital long QT syndrome (LQTS). Twenty-two congenital LQTS patients and 30 control subjects were included in this study. We measured serum Mg (SMg) level and Mg retention (MgR) level, and evaluated the role of Mg (a high MgR level reflects Mg deficiency in the body). The influence of intravenous Mg infusion on Mg level was evaluated. Relatively low SMg level and high MgR level (LQTS:control = 53:33%, p < 0.01) were recognized in congenital LQTS patients, but there was an overlap with controls. Mg supplementation did not shorten QT interval and there was no significant correlation between Mg levels and QTc interval. Patients with syncopal history showed a higher MgR level (syncope (+):syncope (-) = 70:46%, p < 0.01) and intravenous Mg infusion improved Mg deficiency. These results suggest that some (not all) congenital LQTS patients are in a Mg-deficient state, which may be associated with syncope, and Mg supplementation may prevent recurrent syncope in these patients. Because there are several subtypes of congenital LQTS, perhaps with genetic testing Mg deficiency may be identified as a significant cofactor in some forms, whereas in other forms it is not relevant.     

Developmental changes in cyclooxygenase mRNA expression in the gastric mucosa of rats

BACKGROUND: In newborn rats, gastric mucosa is more susceptible to various damaging agents and recovers from injury more quickly than in older animals. To determine whether metabolism of prostaglandins is responsible for this mucosal protective mechanism in developing rats, we studied cyclooxygenase (COX) mRNA expression in the mucosa using quantitative real-time polymerase chain reaction (PRC). METHODS: Cyclooxygenase-1 and COX-2 mRNA was extracted from the gastric mucosa of rats of various ages and quantitatively analyzed using real-time PCR with dual-labeled fluorogenic probes. The copy numbers of cDNA for COX-1 and COX-2 were standardized to glyceraldehyde-3-phosphate dehydrogenase from the same sample. RESULTS: Cyclooxygenase-1 mRNA expression was lowest in 1-week-old rats and highest in 4-week-old rats. Mucosal damage produced by 150 mmol/L HCl and 60% ethyl alcohol did not increase COX-1 mRNA expression in any age group. Cyclooxygenase-2 mRNA expression increased significantly with age. Mucosal injury increased COX-2 mRNA in each age group, especially in 1-week-old rats. Intraperitoneal lipopolysaccharide also increased COX-2 mRNA in both 1- and 4-week old rats. CONCLUSION: The high level of COX-2 mRNA expression in the gastric mucosa of 1-week-old rats may be responsible for the physiologic characteristics of gastric mucosal defenses in this age group.     

Localization of intestinal intraepithelial T lymphocytes involves regulation of alphaEbeta7 expression by transforming growth factor-beta

Induction of alphaEbeta7 expression on T cells by transforming growth factor (TGF)-beta is thought to be important for intestinal intraepithelial T lymphocyte (IEL) entry into the epithelial compartment. However, there has been no in vivo evidence that up-regulation of alphaEbeta7 expression on T cells by TGF-beta is critical for the selective localization of intestinal IEL in the epithelial area. We have recently established transgenic mice expressing Smad7 under the control of a distal lck promoter where TGF-beta/Smad signaling is specifically blocked in mature T cells. Here we showed that TGF-beta-mediated up-regulation of alphaEbeta7 was impaired on T cells isolated from the Smad7 transgenic mice associated with reduced numbers of intestinal IEL when compared with that in wild-type littermates. These results indicated that failure to induce alphaEbeta7 on T cells by TGF-beta resulted in reduced numbers of intestinal IEL, suggesting the importance of alphaEbeta7 expression by TGF-beta in selective localization of intestinal IEL.     

Dense bone island: clinical features and possible complications

Summary. A case of dense bone island in a girl aged 10 years, 1 month old is presented. The lesion was asymptomatic and was an incidental finding on a radiograph taken for another purpose. Nine months after the patient's first visit, an obvious inclination of adjacent teeth was identified. The size and density of the lesion had increased by 10 and 7%, respectively. As the patient was still in adolescence, the lesion may increase in size and density, potentially resulting in further problems such as increased inclination of the adjacent teeth. In addition, the presence of the lesion may complicate any future orthodontic treatment. The lesion should be kept under observation until its growth ceases.     

Spontaneous communication between a simple renal cyst and the pyelocaliceal system with a gas-producing infection

We present the extremely rare case of a 44-year-old woman who presented with right flank pain and high fever, which proved to be a case of spontaneous communication between a renal cyst and the pyelocaliceal system caused by increased pressure in the renal pelvic cavity exerted by a stone leading to infection.