Penile keratoacanthoma associated with urothelial carcinoma of the bladder in Muir-Torre syndrome

A combination of some specific skin tumors with visceral cancers characterize Muir-Torre syndrome. A 60-year-old male patient who presented with penile keratoacanthoma accompanied by bladder and colorectal cancer is presented.     

Comparison of pulse and oral steroid in childhood membranoproliferative glomerulonephritis

BACKGROUND: There has been no controlled study comparing efficacy of pulse versus oral steroid therapy in childhood membranoproliferative glomerulonephritis (MPGN). This study aimed to compare these therapies and renal outcome over a long-term period for MPGN. METHODS: Outcome measures in 11 patients with MPGN treated with pulse methylprednisolone (MP) were compared with 8 patients with MPGN treated with oral prednisolone (P). RESULTS: Nineteen children with idiopathic MPGN (mean age 9.75 years, range 3.7-14 years) were followed for a mean period of 68.21 months (range 4-124 months). Both treatment groups were similar in demographic, clinical, laboratory and histopathological characteristics on presentation. In the pulse MP group, only 1 patient out of 11 progressed to end-stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group (p=0.041). For long-term renal survival, those patients with more than 8 years of follow-up were further evaluated. Twelve patients had completed 8 years of follow-up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5 patients in the oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation biopsy and lack of remission in patients with nephrotic syndrome (NS) were positively associated with adverse renal outcome (p=0.02, p=0.006, respectively). CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with MPGN in preserving renal function without any increase in steroid-related side effects. Chronic damage in the presentation biopsy and lack of remission of NS are adverse features.     

Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity

Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P < 0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P < 0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.     

Simultaneous gradient-echo/spin-echo EPI of graded ischemia in human skeletal muscle

The goal of this study was to evaluate the usefulness of blood oxygenation level-dependent (BOLD) methodologies to provide temporal and spatial information about skeletal muscle perfusion. A simultaneous gradient echo (GE) and spin-echo (SE) imaging sequence (GE/SE) with alternating TE was used to acquire images of leg skeletal muscle throughout a stepped reactive hyperemia paradigm. The change in both the GE and SE relaxation rates (ΔR2*, ΔR2) measured during ischemia and reactive hyperemia scaled with the duration of cuff inflation (the ischemic period) plateaued for cuff inflations lasting longer than 120 seconds and were greater in soleus muscle than in gastrocnemius. The ratio ΔR2*/ΔR2 was found to be less during the reactive hyperemia period relative to ischemia. Considering that a greater proportion of capillary vessels are perfused during reactive hyperemia than during ischemia, this finding suggests that magnetic susceptibility methodologies, with their dependence on compartment size, may provide a measure of the relative distribution of small and large vessels in skeletal muscle.     

Effect of age on the response to short-term partial bladder outlet obstruction in the rabbit

OBJECTIVE: To compare the physiological and structural changes after short-term partial bladder outlet obstruction (PBOO) in young and old rabbits, as PBOO results in marked contractile and histological alterations in the bladder. MATERIALS AND METHODS: In all, 20 young (7-8-week-old) and 20 old (2 years old) male rabbits were divided into four subgroups of five each (four obstructed and one sham control rabbit). The rabbits in the groups were evaluated after 1, 3, 7 and 14 days of PBOO, respectively. At the end of the respective periods, cystometry and contractile responses to field stimulation (FS), ATP, carbachol and potassium chloride were determined. Full-thickness sections of the bladder body and base were used to determine the vascular density, nerve density and smooth muscle/collagen ratios. RESULTS: The bladder weight of young rabbits increased at 1-7 days of PBOO and returned toward control levels at 14 days of PBOO, while in old rabbits it was higher than the control during the entire experiment. For the young rabbits, the responses to field stimulation decreased progressively for 1, 3 and 7 days, and increased significantly at 14 days. For old rabbits there was a progressive decrease to a minimal response by 3 days of PBOO and the response remained at this level over 14 days. The contractile response to ATP, carbachol and KCl were similar to the responses to FS. The vascular density in both groups increased to a maximum at 7 days and then decreased toward control values at 14 days. For the young rabbits, nerve density decreased more than in old rabbits. In the old group, the smooth muscle/collagen ratio was increased throughout PBOO and was higher than in young rabbits. The connective tissue compartment was markedly greater than in the young rabbits and the basal mucosa had vacuoles which were not apparent in the young bladders. CONCLUSIONS: This study shows that the adaptive changes to PBOO are faster in young rabbit bladders than in older rabbits.     

Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin.

Obesity is a complex disease with multiple features that has confounded efforts to unravel its pathophysiology. As a means of distinguishing primary from secondary characteristics, we compared levels of fasting plasma leptin and insulin in a cohort of weight-reduced obese women who have attained and maintained a normal BMI for more than 1 year with the levels in cohorts of never-obese and currently obese women. Weight-reduced obese women showed decreased plasma concentrations of leptin and insulin compared with obese women, but these levels remained significantly higher than those of never-obese women. Plasma leptin levels were highly correlated with plasma insulin levels (r = 0.60, P < 0.001). To further explore relationships with body composition, total body fat was determined by dual-energy X-ray absorptiometry and body fat distribution by computed tomography in subsets of these groups. Weight-reduced obese women had a significantly greater percent body fat and subcutaneous abdominal fat mass than did the never-obese women, and these were highly correlated with plasma leptin (r = 0.90, P < 0.001, and r = 0.52, P < 0.001, respectively). In these weight-reduced obese women, visceral fat mass was similar to that of the never-obese. The insulin sensitivity index and first-phase insulin response were also comparable. These results demonstrate that higher leptin levels in weight-reduced obese women are related to the higher total fat and particularly the subcutaneous fat masses. Normalization of visceral fat mass in the weight-reduced obese was accompanied by normalization of insulin sensitivity index and first-phase insulin response. This study suggests that increases in plasma leptin and insulin in obesity are secondary features of the obese state.     

Relationship between SP1 polymorphism and osteoporosis in β-thalassemia major patients

Background: β-Thalassemia is an autosomal recessive disease characterized by defective β-globin chain production. Osteoporosis is an important cause of morbidity in patients with β-thalassemia major. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetics factors have been implicated in other populations of patients with osteoporosis. Polymorphism at the Sp1 binding site of the collagen type I A1 ( COLIA1 ) gene is thought to be an important factor in the development of osteoporosis.
Methods: Alleles S and s , detected by presence of a G or T nucleotide, respectively in a regulatory site of the COLIA1 gene were investigated in 37 β-thalassemia major patients with osteoporosis and 92 controls without osteoporosis or osteopenia using polymerase chain reaction–restriction fragment length polymorphism.
Results: Fifteen and nine β-thalassemia major patients displayed SS and Ss genotypes, respectively, whereas 13 were found to have an ss genotype. The mean BMD of the β-thalassemia major patients with ss genotype was similar to those with the Ss and SS genotypes. In the control group, 77 and 15 subjects had SS and Ss genotypes, respectively, with no ss genotype. Allelic and genotypic distribution in patients were significantly different from controls.
Conclusion: Determining base substitutions at the Sp1 binding site on the COLIA1 gene in early years may be important in preventing osteoporosis in children with β-thalassemia major.     

Analysis of NKX3.1 expression in prostate cancer tissues and correlation with clinicopathologic features

This study aimed to analyze NKX3.1 expression in tissue samples of benign prostate hyperplasia (BPH) and in three different prostate cancer categories. The correlation of NKX3.1 expression with clinical and pathologic features of patients having undergone radical prostatectomy also was investigated. NKX3.1 expression was determined in tissue samples obtained from four different histopathological categories: (1) from patients treated with transurethral prostatectomy for BPH (n = 26), (2) localized prostate cancer patients subjected to radical prostatectomy (n = 38), (3) biopsy samples from prostate cancer patients who were metastatic at the initial admission (n = 10), and (4) tissue samples of prostate cancer patients administered antiandrogens, but who had undergone transurethral prostatectomy for infravesical obstruction (n = 11). Standard immunohistochemical staining was performed using an antiserum raised against recombinant human NKX3.1. Staining was seen in all categories of prostatic tissues. Immunohistochemistry staining scores were lower in prostate cancer patients. The staining scores were significantly higher in patients with BPH compared to metastatic or localized prostate cancer patients. Staining scores of patients with BPH and of those under antiandrogen therapy were similar. No significant correlation was found between NKX3.1 expression and tumor volume, Gleason sum scores, the presence of extraprostatic extension, tumor stage, or serum PSA. NKX3.1 expression is significantly decreased in prostate cancer patients when compared to BPH. However, the decline of NKX3.1 expression was not correlated with prostate cancer progression and was not associated with advanced stage. Thus, NKX3.1 expression is not a clinically valuable prognostic factor.