Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.     

Changes in plasma retinol of American kestrels (Falco sparverius) in response to dietary or in ovo exposure to environmentally relevant concentrations of a penta-brominated diphenyl ether mixture, DE-71

Polybrominated diphenyl ethers (PBDE) are ubiquitous, lipophilic, and bioaccumulative brominated flame retardants. Plasma retinol concentrations of captive adult American kestrels were assessed at the beginning of the breeding season following 3 wk of daily dietary exposure to vehicle (control), low (0.3 ng/g wet weight [ww]), or high (1.6 ng/g ww) concentrations of DE-71 and in their 25-d-old nestlings following embryonic exposure by maternal deposition to environmentally relevant low (291 ± 48 ng/g ww) or high (1111 ± 160 ng/g ww) sum (Σ) PBDE concentrations. Unexpectedly, low in ovo concentrations of total-α-hexabromocyclododecane (HBCD) were detected. Plasma retinol concentrations of adult males exposed to higher DE-71 concentrations were negatively correlated with in ovo ΣPBDE, BDE-100, and HBCD levels. Maternal (13%) and nestling (11%) retinol levels were lower in the low-exposure group compared to respective controls, and biologically significant since their retinol levels were correlated with hatching success and growth, respectively. Maternal retinol levels were also correlated with BDE-153. The underlying mechanisms may involve (1) PBDE exposure, hydroxylated (OH-) metabolites, and subsequent changes in retinol mobilization; (2) decreased maternal food consumption; and (3) reduced maternal retinol yolk deposits. The apparent lack of retinol changes in the high-exposure kestrel may reflect compensation occurring, either by increased mobilization and transportation of retinol, and/or higher food consumption in these birds. When highly mobile as evidenced during reproduction or development, retinol concentrations of adult and nestling kestrels are sensitive to environmentally relevant PBDE and HBCD levels.     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

Cloning of cDNA coding for connective tissue activating peptide III from a human platelet-derived lambda gt11 expression library

We report here the cloning of the cDNA coding for platelet connective tissue-activating peptide-III (CTAP-III) from a lambda gt11 expression library prepared using messenger RNA (mRNA) isolated from human platelets. The open reading frame of the clone coded for a protein with 128 amino acid residues. Since the precursor of CTAP-III, platelet basic protein (PBP is 94 amino acids long, the 5'-translated region of the cDNA codes for a leader sequence 34 amino acids long. This leader sequence, like the sequence of mature CTAP-III, shows significant homology to the sequence of platelet factor 4 (PF4), the only other platelet specific alpha-granule protein cloned until now, from a human erythroleukemic (HEL) cell line-derived cDNA library. These leader sequences are probably critical for targeting such proteins to the alpha-granule. Northern blot hybridization with platelet and megakaryocyte mRNA shows a single species mRNA of approximately 0.8 kb, suggesting that the corresponding cDNA is full length. The cloning of platelet specific CTAP-III provides additional evidence for the platelet specificity of the cDNA library used.