Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy

In a distinct autosomal recessive variant of epidermolysis bullosa, EB- MD, life-long skin blistering is associated with late-onset muscular dystrophy of unknown etiology. Electron microscopy of these patients' skin suggests that tissue separation occurs intracellularly at the level of the hemidesmosomal inner plaque, which contains plectin, a high molecular weight cytoskeletal associated protein, also expressed in the sarcolemma of the muscle. In this study, we report two patients with EB-MD, each with a homozygous deletion mutation in the plectin gene, PLEC1. In the first case, the proband and her similarly affected sister had a homozygous 9 bp deletion mutation, designated as 2719de19, which resulted in elimination of three amino acids, QEA, in a sequence of 23 amino acids entirely conserved between the mouse and human sequences. The proband in the second family demonstrated a single nucleotide deletion at position 5866, designated as 5866delC, which resulted in frameshift and a premature termination codon for translation 16 bp downstream from the site of deletion. The absence of plectin in the hemidesmosomes, as reflected by negative immunofluorescence with an anti-plectin antibody (HD-1), associated with fragility of basal keratinocytes, implicates plectin as critical for binding of intermediate keratin filament network to hemidesmosomal complexes. The function of plectin as a putative attachment protein also in the muscle would explain the clinical phenotype consisting of cutaneous fragility and muscular dystrophy in EB-MD.      

Perceived prevalence of peanut allergy in Great Britain and its association with other atopic conditions and with peanut allergy in other household members

BACKGROUND: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two-stage interview survey conducted in Great Britain. METHODS: A total of 16434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow-up interviews were conducted with identified sufferers from peanut allergy (stage 2). RESULTS: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%-0.55%). The prevalence in children (0.61%, 0.41%-0.82%) was slightly higher than in adults; age-of-onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree-nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. CONCLUSIONS: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to demographic factors, other food allergies, atopic conditions, and allergy in family/household members. Our study comprised a screening survey and detailed interviews with sufferers identified. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management [corrected].     

Automated sequencing detects all mutations in Northern Irish patients with phenylketonuria and mild hyperphenylalaninaemia

In the first phase of the Northern Ireland PKU Study, we used automated sequencing to identify the spectrum of mutations in a random group of 32 unrelated phenylketonuria (PKU) families. We also investigated 7 Northern Irish patients with mild hyperphenylalaninaemia not requiring dietary intervention (MHP, previously referred to as non-PKU HPA). Disease-causing mutations were identified on all 78 investigated chromosomes. We found 23 different mutations, including 20 missense, 1 nonsense and 2 splice site mutations. All mutations were located within exons or at intronexon boundaries of the phenylalanine hydroxylase gene. Seven mutations occurred at CpG sites, confirming these sites as mutation hot-spots in PKU. Mutations R408W and I65T are the two commonest PKU mutations in the Northern Irish population. Two mutations (T380M and V245A) can be characterized as MHP mutations; they are quasi dominant markers for MHP since they cause mild hyperphenylalaninaemia even when occurring in conjunction with the most severe PKU mutations. The results have proven valuable for the development of a routine PKU mutation analysis system in Northern Ireland.     

Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study) [see comments]

A deficiency of protein C (PC), antithrombin, or protein S is strongly associated with deep-vein thrombosis in selected patients and their families. However, the strength of the association with venous thrombosis in the general population is unknown. This study was a population-based, patient-control study of 474 consecutive outpatients, aged less than 70 years, with a first, objectively diagnosed, episode of venous thrombosis and without an underlying malignant disease, and 474 healthy controls who matched for age and sex. Relative risks were estimated as matched odds ratios. Based on a single measurement, there were 22 (4.6%) patients with a PC deficiency (PC activity, less than 0.67 U/mL or PC antigen, less than 0.33 U/mL when using coumarins). Among the controls, the frequency was 1.5% (seven subjects). Thus, there is a threefold increase in risk of thrombosis in subjects with PC levels below 0.67 or 0.33 U/mL [matched odds ratio, 3.1; 95% confidence interval (CI), 1.4 to 7.0]. When a PC deficiency was based on two repeated measurements, the relative risk for thrombosis increased to 3.8 (95% CI, 1.3 to 10); when it was based on DNA-confirmation, the relative risk increased further to 6.5 (95% CI, 1.8 to 24). In addition, there was a gradient in thrombosis risk, according to PC levels. The results for antithrombin are similar to those for PC, although less pronounced (relative risk, 2.2; 95% CI, 1.0 to 4.7). We could not find an association between reduced total protein S (relative risk, 0.7; 95% CI, 0.3 to 1.8) or free protein S levels (relative risk, 1.6; 95% CI, 0.6 to 4.0) and thrombosis risk. Although not very frequent, PC and antithrombin deficiency are clearly associated with an increase in thrombosis risk.     

三维超声心动图测定左心耳容量及其收缩功能的初步研究

目的　观察三维超声心动图测定左心耳容量的可行性。方法　对 10名患者行多平面经食管超声心动图 (TEE)检查。应用三维超声心动图采取圆盘总和方法 (disksummation)测定左心耳舒张末期容量 (EDV)和左心耳收缩末期容量 (ESV)。用二维超声心动图测定左心耳舒张末期面积 (EDA)和左心耳收缩末期面积(ESA)。上述左心耳容量和面积的测定均在二个独立的观察者之间以及同一观察者两次观察间重复进行。由三维超声心动图容量测定结果计算出左心耳的射血分数 (EFv) ,由二维超声心动图的面积测定结果计算出左心耳射血分数 (EFa)。结果　三维超声心动图测定左心耳EDV为 ( 19.5± 10 .9)ml,ESV为 ( 13 .5± 9.5 )ml ,EFv为0 .3 5± 0 .14。二维超声心动图测定左心耳EDA为 ( 8.7± 2 .2 )cm2 ,ESV为 ( 5 .9± 3 .5 )cm2 ,EFa为 0 .3 5± 0 .2 2。以上测量内容在观察者之间及观察者内的重复性检验中均未见显著性差异 ,EFv与EFa之间亦无显著性差异。但无论在观察者间或观察者内的重复性检验中EFa的范围和两测量数值之差均大于EFv的相应值。结论　三维超声心动图测量左心耳容量和评价其收缩功能是可行的 ,这种测定方法可能有助于改善二维超声心动图评价左心耳功能的准确性。     

Arterial disease in lupus and secondary antiphospholipid syndrome: association with anti-beta2-glycoprotein I antibodies but not with antibodies against oxidized low-density lipoprotein

The prevalence and clinical significance of antibodies against beta2- glycoprotein I (anti-beta2GPI) and antibodies against oxidized low- density lipoprotein (anti-ox-LDL) were evaluated as potential indicators of arterial disease in patients with systemic lupus erythematosus (SLE) and SLE with secondary antiphospholipid syndrome (APS). IgG anti-beta2GPI and IgG anti-ox-LDL were measured by enzyme- linked immunosorbent assay (ELISA) in serum samples from 118 patients with SLE, including 40 with secondary APS. IgG anti-beta2GPI were positive in 17% (20/118) of SLE patients. The presence and titres of IgG anti-beta2GPI were strongly associated with a history of arterial thrombosis. Haemolytic anaemia was also significantly associated with the presence of IgG anti-beta2GPI. The prevalence of IgG anti-ox-LDL was 53% (63/118), but there was no association with arterial thrombosis. No correlation between the values of anti-ox-LDL and those of anti-beta2GPI was found. These results suggest that IgG anti- beta2GPI could be a marker for arterial thrombosis in SLE patients, while IgG anti-ox-LDL were not associated with arterial disease in this group of lupus patients.      

An update on the implications of cyclin D1 in oral carcinogenesis

Cyclin D1 promotes cell cycle progression during G1 phase, a key event in G1‐S transition. The protein is encoded by gene CCND1, located in chromosomal band 11q13. Cyclin D1 plays key roles in cell biology, including cell proliferation and growth regulation, mitochondrial activity modulation, DNA repair, and cell migration control. CCND1 gene and its protein cyclin D1 are frequently altered by different molecular mechanisms, including amplification, chromosomal translocations, mutations, and activation of the pathways involved in cyclin D1 expression, alterations which appear to be essential in the development of human cancers, including oral carcinoma. This is the first published review of the specific features of cyclin D1 overexpression in oral oncogenesis. Starting with the physiological regulation of cyclin D1, there is an evaluation of its functions, overexpression mechanisms, and the implications of the oncogenic activation of CCND1/cyclin D1 in oral squamous cell carcinoma . The potential diagnostic and prognostic value of cyclin D1 is reviewed. The influence of CCND1/cyclin D1 on tumor size and clinical stage is reported, and an update is provided on the utilization of cyclin D1 as therapeutic target and on the combination of cyclin D1 inhibitors with cytotoxic agents. Future research lines in this field are also proposed.     

100 classic papers of interventional radiology: A citation analysis

AIM: To define the 100 citation classic papers of interventional radiology.METHODS: Using the database of Journal Citation Reports the 40 highest impact factor radiology journals were chosen. From these journals the 100 most cited interventional radiology papers were chosen and analysed.RESULTS: The top paper received 2497 citations and the 100 th paper 200 citations. The average number of citations was 320. Dates of publication ranged from 1953- 2005. Most papers originated in the United States(n = 67) followed by Italy(n = 20) and France(n = 10). Harvard University(n = 18) and Osped Civile(n = 11) were the most prolific institutions. Ten journals produced all of the top 100 papers with "Radiology" and "AJR" making up the majority. SN Goldberg and T Livraghi were the most prolific authors. Nearly two thirds of the papers(n = 61) were published after 1990.CONCLUSION: This analysis identifies many of the landmark interventional radiology papers and provides a fascinating insight into the changing discourse within the field. It also identifies topics, authors and institutions which have impacted greatly on the specialty.