Bone morphogenetic protein 2/SMAD signalling in human ligamentocytes of degenerated and aged anterior cruciate ligaments.

OBJECTIVE: Anterior cruciate ligament (ACL) degeneration leads to knee instability and favors osteoarthritis (OA) progression. During ageing the growth factor sensitivity of ligaments changes but nothing is known about BMP2-signalling and -sensitivity in degenerated ACLs. This study addressed the question whether a dysregulated BMP2 signalling might contribute to age- and OA-dependent ACL degeneration. METHOD: ACL samples from patients with/without OA of different ages (<60 and ≥60 years, males, females) were graded histopathologically (n = 45). After stimulation of cultured ACL fibroblasts with 5 nM BMP2 for different time points, phosphorylation of SMAD1/5/8 and gene expression of crucial BMP2 signalling proteins, ligamentogenic and chondrogenic transcription factors, scleraxis (SCX) and SOX9, were analyzed. RESULTS: ACL samples displayed different grades of degeneration, often associated with synovitis and calcium deposits. Degeneration correlated significantly with synovitis. ACL fibroblasts expressed BMP type I receptors ALK3 and ALK6 and the BMP type II receptor BMPRII. Donors could be divided into "responders" and "non responders" since their BMP2 mediated SMAD1/5/8 phosphorylation level differed. Basal ID1 expression was lower in cells derived from OA compared with non-OA patients and BMP2 led to an ID1 induction in both. Irrespective of BMP2 stimulation, the donor age significantly influenced the expression profile of BMP6 and SCX but not BMP signalling. The BMP2-mediated SMAD6 expression differed between OA and healthy ACL fibroblasts. CONCLUSION: Our data indicate that the expression level of BMP2/SMAD target genes such as ID1 and SMAD6 was reduced in ACL fibroblasts derived from OA compared with non OA patients.

[Evaluation of testicular volume in 0- to 18-year-old boys by sonography]. / Sonographische Bestimmung der Hodenmaße im Alter von 0 bis 18 Jahren.

BACKGROUND: Reference values are necessary in clinical practice in order to correctly evaluate testicular volume and detect disorders. OBJECTIVES: The objective of this prospective cross-sectional study was to evaluate reference values for testicular volume dependent on age, height, and weight in boys aged 0-18 years. MATERIAL AND METHODS: During their inpatient stay, the testes of 174 boys, who were free of disease or therapy that might influence testicular development, were examined by sonography. High resolution ultrasound transducers ranging from 7.5-14 MHz were used for evaluation. The testicular volume was calculated by the ellipsoid formula: length • width • height • (π/6). RESULTS: The subject age ranged from 0-18 years (average 7.1 ± 5.3 years). At the age of 0-8 years, the left testicular volume (1.2 ml) was less than the right testicular volume (1.3 ml). At the age of 13 years, the testicular volume of all subjects was over 3 ml. Left testicular volume of boys aged 16.5-18 years ranged from 7 to 22 ml and the right testicular volume ranged from 6 to 22 ml. CONCLUSION: Reference value tables of testicular volume dependent on age, and for the first time dependent on weight and height in boys aged from 0-18 years were compiled. Tables of testicular length, width, and height dependent on age are provided.

Evaluation of the prognostic meaning of C-reactive protein (CRP) in children and adolescents with classical Hodgkin's lymphoma (HL).

BACKGROUND: In adult cancer patients the negative predictive value of elevated CRP levels has been described for several malignancies. Only few studies have analyzed the prognostic role of CRP in children and adolescents with classical HL. In these studies elevated CRP levels correlate with the presence of classical risk factors and adverse outcome. PATIENTS AND METHODS: The prognostic role of CRP for patients with classical HL admitted to the GPOH-HD-2002 study was analyzed retrospectively. RESULTS: CRP levels were documented for 369 of 573 patients. Significant (p<0.05) increased median CRP levels were found in the presence of B-Symptoms (25.7 vs. 5.1 mg/l), extranodal involvement (21.5 vs. 7.5 mg/l), elevated erythrocyte sedimentation rate (ESR, 13.0 vs. 1.0 mg/l) and stage III/IV disease (15.5 vs. 5.3 mg/l). 83.9% of patients with elevated and 45.8% of patients with normal CRP had an ESR >30 mm/h. CONCLUSION: Elevated CRP levels were associated with classical risk factors of HL. CRP and ESR may reflect different biological processes. CRP was prognostic within early stage TG-1 patients treated with reduced treatment, but not within advanced stage TG-2+3.

Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features.

OBJECTIVES: The purpose of this study was to determine the prevalence, clinical signs and radiological features of breast lymphoma. METHODS: This is a retrospective review of 36 patients with breast lymphoma (22 primary and 14 secondary). 35 patients were female and 1 was male; their median age was 65 years (range 24-88 years). In all patients, the diagnosis was confirmed histopathologically. RESULTS: The prevalence of breast lymphoma was 1.6% of all identified cases with non-Hodgkin lymphoma and 0.5% of cases with breast cancer. B-cell lymphoma was found in 94% and T-cell lymphoma in 6%. 96 lesions were identified (2.7 per patient). The mean size was 15.8 ± 8.3 mm. The number of intramammary lesions was higher in secondary than in primary lymphoma. The size of the identified intramammary lesions was larger in primary than in secondary lymphoma. Clinically, 86% of the patients presented with solitary or multiple breast lumps. In 14%, breast involvement was diagnosed incidentally during staging examinations. CONCLUSION: On mammography, intramammary masses were the most commonly seen (27 patients, 82%). Architectural distortion occurred in three patients (9%). In three patients (9%), no abnormalities were found on mammography. On ultrasound, the identified lesions were homogeneously hypoechoic or heterogeneously mixed hypo- to hyperechoic. On MRI, the morphology of the lesions was variable. After intravenous administration of contrast medium, a marked inhomogeneous contrast enhancement was seen in most cases. On CT, most lesions presented as circumscribed round or oval masses with moderate or high enhancement.

Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans.

AIMS/HYPOTHESIS: Recently, FTO was identified as a candidate gene contributing to both childhood and severe adult obesity. We tested the hypothesis that mRNA expression of FTO and/or of the neighbouring RPGRIP1L in adipose tissue correlates with measures of obesity and fat distribution. We also investigated whether the FTO obesity risk alleles might explain variability in FTO and RPGRIP1L mRNA expression. METHODS: In paired samples of visceral and subcutaneous adipose tissue from 55 lean and obese participants, we investigated whether FTO and RPGRIP1L mRNA expression is fat depot-specific, altered in obesity and related to measures of fat accumulation, insulin sensitivity and glucose metabolism. All participants were genotyped for the obesity-associated rs8050136 FTO variant. RESULTS: FTO mRNA expression was threefold higher in subcutaneous than in visceral adipose tissue. Subcutaneous FTO expression correlated with visceral FTO expression. FTO gene expression in both depots correlated with age and was negatively correlated to BMI and per cent body fat. FTO mRNA levels were not related to measures of insulin sensitivity and glucose metabolism. RPGRIP1L mRNA expression was 1.6-fold higher in visceral than in subcutaneous adipose tissue, but did not correlate with anthropometric and metabolic characteristics. There was no association between rs8050136 and FTO or RPGRIP1L mRNA expression in adipose tissue. CONCLUSIONS/INTERPRETATION: Expression of adipose tissue FTO mRNA is fat depot-specific and negatively correlates with measures of obesity. However, the direction of this relationship still needs to be elucidated.

Adipose triglyceride lipase gene expression in human visceral obesity.

In comparison to subcutaneous (SC) fat, visceral adipose tissue is more sensitive to catecholamine-induced lipolysis and less sensitive to the antilipolytic effects of insulin. Variation in the expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) have been reported. We therefore hypothesized that expression of adipose triglyceride lipase (ATGL) is different in visceral and SC depot and investigated whether ATGL mRNA expression is related to obesity, fat distribution and insulin sensitivity. ATGL, LPL, and HSL mRNA expression was measured in 85 paired samples of omental and subcutaneous adipose tissue in normal glucose tolerant lean and obese individuals. In addition, we included a subgroup of obese (BMI >30 kg/m2) individuals with either impaired or preserved insulin sensitivity determined by euglycemic-hyperinsulinemic clamps. ATGL mRNA levels are significantly decreased in insulin resistant obese subjects. Independently of body fat mass, omental ATGL mRNA correlates with fasting insulin concentration, glucose uptake during the steady state of the clamp and HSL mRNA expression. In obese, but not in lean subjects, LPL and HSL mRNA expression was significantly higher in omental compared to SC fat. In both depots, HSL mRNA was significantly lower in obese individuals. Visceral HSL mRNA expression is closely related to adipocyte size and fasting plasma insulin concentrations, whereas visceral fat area significantly predicts visceral LPL mRNA expression. ATGL mRNA expression is not significantly different between omental and SC fat. HSL, but not ATGL mRNA expression is closely related to individual and regional differences in adipocyte size. Impaired insulin sensitivity was associated with decreased ATGL and HSL mRNA expression, independently of body fat mass and fat distribution.

Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Increased expression and activity of the lipogenic pathways in adipose tissue may contribute to the development of obesity. As a central enzyme in lipogenesis, the gene encoding fatty acid synthase (FASN) was identified as a candidate gene for determining body fat. In the present study we tested the hypothesis that increased FASN expression links metabolic alterations of excess energy intake, including hyperinsulinaemia, dyslipidaemia and altered adipokine profile to increased body fat mass. SUBJECTS AND METHODS: In paired samples of visceral and subcutaneous adipose tissue from 196 participants (lean or obese), we investigated whether FASN mRNA expression (assessed by PCR) in adipose tissue is increased in obesity and related to visceral fat accumulation, measures of insulin sensitivity (euglycaemic-hyperinsulinaemic clamp) and glucose metabolism. RESULTS: FASN mRNA expression was increased by 1.7-fold in visceral vs subcutaneous fat. Visceral adipose tissue FASN expression was correlated with FASN protein levels, subcutaneous FASN expression, visceral fat area, fasting plasma insulin, serum concentrations of IL-6, leptin and retinol-binding protein 4 (RBP4), and inversely with measures of insulin sensitivity, independently of age, sex and BMI. Moreover, we found significant correlations between FASN expression and markers of renal function, including serum creatinine and urinary albumin excretion. CONCLUSIONS/INTERPRETATION: Increased FASN gene expression in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, IL-6, leptin and RBP4, suggesting an important role of lipogenic pathways in the causal relationship between consequences of excess energy intake and the development of obesity and type 2 diabetes.