Targeted disruption of mouse centromere protein C gene leads to mitotic disarray and early embryo death

Centromere protein C (CENPC) is a key protein that has been localized to the inner kinetochore plate of active mammalian centromeres. Using gene targeting techniques, we have disrupted the mouse Cenpc gene and shown that the gene is essential for normal mouse embryonic development. Heterozygous mice carrying one functional copy of the gene are healthy and fertile, whereas homozygous embryos fail to thrive. In these embryos, mitotic arrest and gross morphological degeneration become apparent as early as the morula stage of development. The degenerating embryos demonstrate highly irregular cell and nuclear morphologies, including the presence of a large number of micronuclei. Mitotic chromosomes of these embryos display a scattered and often highly condensed configuration and do not segregate in an ordered fashion. These results describing the phenotype of the mutant mouse embryos indicate that CENPC has a direct role in the mitotic progression from metaphase to anaphase.     

Classification of cardiac patient states using artificial neural networks

Electrocardiogram (ECG) is a nonstationary signal; therefore, the disease indicators may occur at random in the time scale. This may require the patient be kept under observation for long intervals in the intensive care unit of hospitals for accurate diagnosis. The present study examined the classification of the states of patients with certain diseases in the intensive care unit using their ECG and an Artificial Neural Networks (ANN) classification system. The states were classified into normal, abnormal and life threatening. Seven significant features extracted from the ECG were fed as input parameters to the ANN for classification. Three neural network techniques, namely, back propagation, self-organizing maps and radial basis functions, were used for classification of the patient states. The ANN classifier in this case was observed to be correct in approximately 99% of the test cases. This result was further improved by taking 13 features of the ECG as input for the ANN classifier.     

Echocardiographic characteristics of professional football players

OBJECTIVES: We examined the echocardiographic characteristics of highly trained American football players. BACKGROUND: Intense physical training is associated with morphologic and physiologic cardiac changes often referred to as the "athlete's heart." Echocardiographic features peculiar to elite football players have not been described. METHODS: We studied cardiac morphology and function as assessed by rest and stress echocardiography in 156 asymptomatic National Football League players. Resting and stress ejection fraction (EF), wall thickness, and diastolic left ventricular internal diameter (LVID) were measured. Left ventricular (LV) mass was calculated, as was relative wall thickness (RWT) defined as septal and posterior wall thickness divided by LVID. Control data were obtained from published studies. RESULTS: The mean LVID (53 +/- 0.5 mm) and maximal wall thickness (11.2 +/- 0.2 mm) were increased over normal reported control subjects. There was a correlation between LVID and body weight (p = 0.01) and body surface area (BSA) (p = 0.01). The average LVID indexed to BSA was 23 +/- 2 mm/M(2). There was also a correlation between maximal wall thickness and body weight (p = 0.01) and BSA (p = 0.01). The average wall thickness indexed to BSA was 5.05 +/- 0.88 mm/M(2). Of the players, 23% had evidence of LV hypertrophy. Two players had an increased septal-to-posterior-wall-thickness ratio (> or =1.3), although no player had an outflow gradient. The RWT for the players was 0.424 (+/- 0.1). The mean resting EF was 58% (+/- 4.4%), and every player undergoing exercise testing had an appropriate hyperdynamic response in cardiac function. CONCLUSIONS: Both wall thickness and LVID of elite American football players are increased and correlate with body size. There is a high RWT, reflecting an emphasis on strength training. The LV EF was normal and not supranormal, as is sometimes believed. Regardless of the resting EF, all players had hyperdynamic cardiac responses with exercise.     

Purification and characterization of the prothoracicotropic hormone of Drosophila melanogaster

The prothoracicotropic hormone (PTTH) of Drosophila melanogaster is a modulator of ecdysteroid (molting hormone) synthesis and was isolated and characterized from extracts of whole larvae (≈4 × 10⁵ larvae). The purification protocol included delipidation, salt-extraction, heat treatment, conventional column chromatography, and HPLC, and yielded about 50 μg of pure hormone. Biological activity was followed using a ring gland in vitro assay in which ecdysteroidogenesis by control ring glands as measured by radioimmunoassay was compared with ring gland incubations containing active fractions. The molecular weight of the purified PTTH was 45 kDa and N-terminal amino acid sequence analysis indicated that those analyzed sequences displayed no significant homology with known peptides or peptide hormones, including PTTH from the silkmoth, Bombyx mori. Western blot analysis indicated that the native form of Drosophila PTTH was a single 66-kDa polypeptide with N-linked carbohydrate chains and intrachain disulfide bonds. The purified 45-kDa peptide is the deglycosylated form, a result of glycosidase activity present during preparation of the PTTH extract. The deglycosylated form shows heterogeneity, presumably as a result of varying degrees of deglycosylation at the N terminus.     

Peripheral blood flow changes in response to postexercise cold water immersion

This study compared the effect of postexercise water immersion (WI) at different temperatures on common femoral artery blood flow (CFA), muscle (total haemoglobin; tHb) and skin perfusion (cutaneous vascular conductance; CVC), assessed by Doppler ultrasound, near‐infrared spectroscopy (NIRS) and laser Doppler flowmetry, respectively. Given that heat stress may influence the vascular response during cooling, nine men cycled for 25 min at the first ventilatory threshold followed by intermittent 30‐s cycling at 90% peak power until exhaustion at 32·8 ± 0·4°C and 32 ± 5% RH. They then received 5‐min WI at 8·6 ± 0·2°C (WI₉), 14·6 ± 0·3°C (WI₁₅), 35·0 ± 0·4°C (WI₃₅) or passive rest (CON) in a randomized, crossover manner. Heart rate (HR), mean arterial pressure (MAP), muscle (T_mu), thigh skin (T_thigh), rectal (T_re) and mean body (T_body) temperatures were assessed. At 60 min postimmersion, decreases in T_re after WI₃₅ (?0·6 ± 0·3°C) and CON (?0·6 ± 0·3°C) were different from WI₁₅ (?1·0 ± 0·3°C; P<0·05), but not from WI₉ (?1·0 ± 0·3°C; P = 0·074–0·092). WI₉ and WI₁₅ had reduced T_body, T_thigh and T_mu compared with WI₃₅ and CON (P <0·05). CFA, tHb and CVC were lower in WI₉ and WI₁₅ compared with CON (P<0·05). tHb following WI₉ remained lower than CON (P = 0·044) at 30 min postimmersion. CVC correlated with tHb during non‐cooling (WI₃₅ and CON) (r² = 0·532; P<0·001) and cooling recovery (WI₉ and WI₁₅) (r² = 0·19; P = 0·035). WI₉ resulted in prolonged reduction in muscle perfusion. This suggests that CWI below 10°C should not be used for short‐term (i.e. <60 min) recovery after exercise.     

Influence of diabetes mellitus on long-term (five-year) outcomes of drug-eluting stents and coronary artery bypass grafting for multivessel coronary revascularization

Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and for diffuse and progressive atherosclerosis. We evaluated the outcomes of drug-eluting stent (DES) placement and coronary artery bypass grafting (CABG) in 891 diabetic patients (489 for DES implantation and 402 for CABG) and 2,151 nondiabetic patients (1,058 for DES implantation and 1,093 for CABG) with multivessel CAD treated from January 2003 through December 2005 and followed up for a median 5.6 years. Outcomes of interest included death; the composite outcome of death, myocardial infarction (MI), or stroke; and repeat revascularization. In diabetic patients, after adjusting for baseline covariates, 5-year risk of death (hazard ratio 1.01, 95% confidence interval 0.77 to 1.33, p = 0.96) and the composite of death, MI, or stroke (hazard ratio 1.03, 95% confidence interval 0.80 to 1.31, p = 0.91) were similar in patients undergoing DES or CABG. However, rate of repeat revascularization was significantly higher in the DES group (hazard ratio 3.69, 95% confidence interval 2.64 to 5.17, p <0.001). These trends were consistent in nondiabetic patients (hazard ratio 0.80, 95% confidence interval 0.55 to 1.16, p = 0.23 for death; hazard ratio 0.77, 95% confidence interval 0.56 to 1.05, p = 0.10 for composite of death, MI, or stroke; hazard ratio 2.77, 95% CI 1.95 to 3.91, p <0.001 for repeat revascularization). There was no significant interaction between diabetic status and treatment strategy on clinical outcomes (p for interaction = 0.36 for death; 0.20 for the composite of death, MI, or stroke; and 0.40 for repeat revascularization). In conclusion, there was no significant prognostic influence of diabetes on long-term treatment with DES or CABG in patients with multivessel CAD.     

Communication disruption as perceived by significant others of thai aphasic speakers

Abstract

This study investigated the perceptions of significant others (SOs) of Thai aphasic speakers about the communication difficulties that were the most salient to their mutual communication and most disruptive to their day-to-day communication. The SOs were first interviewed and then asked to complete a questionnaire. From both the interview and the questionnaire, verbal expression and pragmatic conversation difficulties were perceived as being more salient to communication breakdown than were auditory comprehension difficulties. Aphasic speakers' word-finding difficulties and the SOs' efforts in keeping conversation going were the specific verbal expression and pragmatic conversational characteristics, respectively, which SOs perceived as most salient and disruptive. A less clear pattern of communication disruption caused by specific auditory comprehension problems was found. Identifying the perceptions of SOs through both interview and questionnaire procedures appeared to have advantages in tapping information about communication disability and handicap that could lend valuable insights in planning ecologically valid intervention.