Rett syndrome is a neurodevelopmental disorder with severe mental retardation caused by mutations in the MECP2 gene. Mutations in the MECP2 gene are also associated with other genetic disorders, ...including X linked mental retardation in males. Missense mutations identified so far are present primarily in the methyl CpG binding domain (MBD) of MECP2. Here, the functional significance of 28 MBD missense mutations identified in patients were analysed by transient expression of the mutant proteins in cultured cells. The effects of mutations were evaluated by analysis of the affinity of MeCP2 to pericentromeric heterochromatin in mouse L929 cells and on transcriptional repressive activity of MeCP2 in Drosophila SL2 cells. These analyses showed that approximately one-third (9/28) of MBD missense mutations showed strong impairment of MeCP2 function. The mutation of the R111 residue, which directly interacts with the methyl group of methyl cytosine, completely abolished MeCP2 function and mutations affecting β-sheets and a hairpin loop have substantial functional consequences. In contrast, mutations that showed marginal or mild impairment of the function fell in unstructured regions with no DNA interaction. Since each of these mutations is known to be pathogenic, the mutations may indicate residues that are important for specific functions of MeCP2 in neurones.
Recent reports on the results of endoscopic ablation of Barrett's mucosa have been promising, particularly when total mucosal ablation is coupled with aggressive acid-suppression treatment using ...high-dose proton-pump inhibitor therapy. There is also a considerable literature on reepithelialization after ablative treatments in Barrett's esophagus. This report describes a case of multifocal superficial adenocarcinoma arising in Barrett's mucosa that was successfully treated with total circumferential endoscopic mucosal resection, with a subsequent follow-up of more than 2 years. This is the first report describing the process of squamous reepithelialization after endoscopic mucosal resection in Barrett's esophagus.
To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images.
Dynamic MR images of breast lesions ...(invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1.
Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis.
Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.
Perineural invasion is regarded as a factor associated with local recurrence of pancreatic cancer.
To examine perineural invasion of pancreatic cancer pathologically and clinically.
In 24 cases of ...surgically resected pancreatic cancer, correlations among the degree of perineural invasion, differentiation, interstitial connective tissue, lymph node metastasis, and survival rate were examined. Consecutive 5-microm serial sections (n = 1072) were made in six cases that showed characteristic mode of perineural invasion.
Perineural invasion was observed in 17 cases (70.8%; ne0-7; ne1-6; ne2-9; and ne3-2 cases). Perineural invasion was absent in three of five cases of papillary carcinoma, but was observed in 12 of 14 cases of moderately differentiated carcinoma. The survival rate for ne0 was better than that of the other groups, with the 3-year survival rate being 57.1%. Perineural cancer glands had developed discontinuously in two cases.
Perineural invasion is an important prognostic factor in pancreatic cancer, increasing as the cancer becomes undifferentiated. Even if there are no cancer cells at the margin of the pancreas at the time of surgery, the cancer cells may spread further to the noncancerous pancreas or retroperitoneum. Sufficient dissection of the neural plexus or intraoperative radiation may be required.
Summary Objective The aim of this study is to develop a rat model of full-thickness articular cartilage defects that is suitable for detailed molecular analyses of the regenerative repair of ...cartilage. Materials and methods The V-shaped full-thickness defects (width: 0.7 mm; depth: 0.8 mm; and length: 4 mm) were created in the femoral patellar groove of 6 weeks old male rats using a custom-built twin-blade device. Prior to starting the repair experiments, our device was examined for its accuracy and reliability in generating defects. Then, the time course of the repair response in these cartilage defects was examined using a semi-quantitative histological grading scale. The expression of chondrogenic differentiation markers in the reparative regions was examined with immunohistochemistry and in situ hybridization. Results Our device creates full-thickness articular cartilage defects uniformly. In these defects, undifferentiated mesenchymal cells filled the defect cavities (4 days) and initiated chondrogenic differentiation at the center of the defect (7 days). Cartilage formation was observed in the same region (2 weeks). Finally, hyaline-like articular cartilage and subchodral bone layers were reconstituted in their appropriate locations (4 weeks). Conclusions We have successfully developed a rat model containing identically sized full-thickness defects of articular cartilage that can undergo chondrogenic repair in a reproducible fashion.
Limited epidemiological evidence suggests that genetic polymorphisms of drug-metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be ...involved in tobacco-related hepatocarcinogenesis. We conducted a case–control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups 275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC, to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group. However, we found a significant interaction (P = 0.0045) between CYP1A2 -3860G>A polymorphism and current smoking on HCC risk when we compared HCC cases with CLD patients; adjusted odds ratios ORs; and 95% confidence intervals (CIs) for G/A and A/A genotypes relative to G/G genotype were 0.28 (0.12–0.66) and 0.18 (0.04–0.94), respectively, among current smokers (P trend = 0.002), as compared with 1.28 (0.80–2.06) and 0.76 (0.34–1.71), respectively, among never/former smokers (P trend = 0.96). Similarly, in CYP1A2 G/G genotype, significant risk increase was observed for current smoking (OR = 4.08, 95% CI = 2.02–8.25) or more recent cigarette use (e.g. pack-years during last 5 years, P trend = 0.0003) but not in G/A and A/A genotypes combined (OR for current smoking = 1.39, 95% CI = 0.63–3.03; P trend for pack-years during last 5 years = 0.40). These results suggest that the CYP1A2 -3860G>A polymorphism modifies the smoking-related HCC risk among CLD patients.
We report three patients with a cerebrovascular accident studied serially by MRI, including diffusion-weighted imaging (DWI). In case 1, DWI 1 day after the onset of left frontoparietal cortical ...infarcts showed no abnormal signal in the left corticospinal tract. DWI 12 days after onset showed high signal in the corticospinal tract, interpreted as early wallerian degeneration. This had disappeared by 22 days after onset. In case 2, DWI obtained 7 days after the onset of a right internal capsule lacunar infarct showed high signal from the right corticospinal tract in the brainstem, which was less marked 15 days after onset. In case 3, MRI on postnatal day 7 showed a cerebral haemorrhage in the right corona radiata and high signal from the right corticospinal tract on DWI. The latter disappeared by day 23. DWI shows early wallerian degeneration; transient signal abnormalities within 2 weeks of stroke should not be mistaken for new ischaemic lesions.
The purpose of this study was to scrutinize morphological characteristics of thin-section CT of the histopathological subtypes of adenocarcinoma of the lung. The subjects consisted of 83 patients ...with 87 adenocarcinomas measuring 3 cm or less in the largest. The tumors were divided into three groups (group I: Noguchi's histological subtypes type A and B tumors, group II: type C tumors, and group III: type D, E, and F tumors). In each group, tumor size, shape (round versus polygonal), presence of air bronchogram, bubble-like areas, coarse spiculation, pleural tag, and ratio of ground glass attenuation (GGA) were evaluated. Most of the group II lesions showed polygonal shape, whereas tumors in other groups were round in shape (P<0.01). Air bronchogram and bubble-like areas of low attenuation was seen more frequently in group II compared with those in group III (P<0.01). GGA areas were largest in group I and smallest in group III (P<0.01). We believe thin-section CT findings reflect the histopathological subtypes of adenocarcinoma of the lung. The presence of air bronchogram and bubble-like areas of low attenuation areas in particular is useful to differentiate replacement growth tumors from non-replacement growth tumors.
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