Revisit on congenital bronchopulmonary vascular malformations: a haphazard branching theory of malinosculations and its clinical classification and implication.

We propose a haphazard branching theory to support the concept of bronchopulmonary malinosculations, and we apply this theory to classify congenital bronchopulmonary vascular malformation (BPVM) based on the anatomical results we have found. Between January 1990 and December 1997, a total of 22 pediatric patients (10 male and 12 female), aged 2 days to 14 years (median, 19.6 months), with congenital BPVM were enrolled in this retrospective study. Study modalities include the clinical features and plain chest films (n = 22) plus at least two of the following: echocardiography (n = 13), barium esophagraphy (n = 2), bronchoscopy (n = 4), contrast bronchography (n = 8), high-resolution direct coronal CT (n = 1) and electron beam or ultrafast CT (n = 1) of the chest, MRI (n = 10), MRA (n = 1), contrast cineangiocardiography (n = 9), surgery (n = 11), or autopsy (n = 2). The salient clinical features were recurrent lung infections in 14 patients, acute respiratory distress in 13, associated cardiovascular malformations in 8, dextroversion in 7, congestive heart failure in 7, dextrocardia in 4, and complex congenital heart diseases in 4. There were abnormal openings (malinosculations) of the pulmonary airway in 20 patients: to an artery in 12, to a vein in 8, and to the lung parenchyma in 9. These 22 patients with congenital BPVM can be classified into bronchial malinosculation (10 cases), arterial malinosculation (2 cases), and bronchoarterial malinosculation (10 cases). Congenital BPVM can be classified in terms of bronchopulmonary malinosculation based upon a haphazard branching theory, in which abnormal communications between two independent systems (primitive foregut system and aortic-pulmonary arch system) occurred coincidentally rather than causally.     

Quantitative processed images acquired by histogram-SNR imaging used to evaluate parenchymal heterogeneity in the liver

Purpose: To evaluate a new system for displaying processed images of liver parenchyma based on quantitative estimation of heterogeneity by texture analysis.Methods: We measured the signal to noise ratio, one of the first-order statistics in the histogram of enveloped amplitude of radio-frequency backscattered echoes, using a 3.75-MHz transducer with texture analysis in conjunction with a new method in which the small ROI (region of interest) is segmented into multiple layers to minimize the influence of tissue attenuation and beam diffraction. In our computerized system, gray-display and color-display images, two types of processed images, were produced from the visual intensity of each small ROI, which was based on its signal to noise ratio. We studied 10 cases of normal liver, 10 cases of fatty liver, and 10 cases of cirrhotic liver. The processed images obtained from these livers were reviewed to observe their features and to compare their usefulness in estimating the heterogeneity of the liver parenchyma with that of conventional B-mode images.Results: Gray-display images of cirrhotic livers appeared much blacker than the images produced from other disorders, and color-display images of cirrhotic liver appeared much bluer or greener than the others. Rate of correct diagnosis from B-mode images was 68.3 ±6.8%; from gray-display images, 85.8±7.4%; and from color-display images, 91.7±8.2%. Rate of correct assessment from B-mode images and gray-display images was significantly correlated (p=0.0015), as was rate of correct assessment from the B-mode images and the color-display images (p=0.0060).Conclusion: The processed images obtained using this computerized system contributed to the correct and objective interpretation of the heterogeneity of the liver parenchyma.     

6-Hydroxydopamine induces thymocyte apoptosis in mice

6-Hydroxydopamine (6-OHDA) induces degeneration of noradrenergic nerves and has been shown to alter the immune responses. In this study, intraperitoneal administration of 6-OHDA induces mouse thymus atrophy. The lowest levels of thymus weight and cell number were reached at days 3 and 5 in mice receiving 6-OHDA treatment; they gradually recovered thereafter. On flow cytometry analysis, the most substantial reductions were recorded for CD4⁺CD8⁺ thymocytes, although the numbers of other subpopulations i.e. CD4⁺CD8⁻, CD4⁻CD8⁺ and CD4⁻CD8⁻ cells were also reduced. DNA fragmentation, a characteristic of apoptosis, was detected in the thymocytes following 6-OHDA injection. Pretreatment with desipramine greatly blocked the reduction in thymus size and thymocyte number, the changes in thymocyte subpopulations, the percentage of subdiploid (apoptotic) cells and the appearance of DNA fragmented bands. Furthermore, 6-OHDA-induced thymocyte apoptosis could also be detected in vitro, and was blocked by desipramine treatment. These results indicate that 6-OHDA induces mouse thymocytes to undergo apoptosis both in vivo and in vitro, and this effect is inhibited by catecholamine uptake blocker.     

Cholesterol-induced upregulation of angiotensin II and its effects on monocyte-endothelial interaction and superoxide production.

Atherogenesis involves an early endothelial dysfunction hallmarked by elevated free radical production and increased adhesiveness for monocytes. It was hypothesized that activation of the tissue renin angiotensin system may contribute to the endothelial alteration. To test this hypothesis, thoracic aortae were isolated from normocholesterolemic (NC; n = 6) and hypercholesterolemic (HC; n = 6; diet: 0.5% cholesterol; 6 weeks) New Zealand white rabbits, and incubated for 2 h with the angiotensin II (Ang II) receptor antagonist Sar-1,Ile-8-Ang II, the antioxidant pyrolidine dithiocarbamate (PDTC) and the protein kinase C (PKC) antagonist staurosporin. Superoxide production from aortic segments was measured by lucigenin-enhanced chemiluminescence. In comparison to the normocholesterolemic state, hypercholesterolemia led to a significant increase in superoxide production (221 +/- 44%, p < 0.02); this was reduced by ex vivo treatment of the vessel segment with Ang II-antagonist (to 130 +/- 29%; p < 0.04 vs HC), or PKC-antagonist (to 86 +/- 26%; p < 0.001 vs HC), or PDTC (to 103 +/- 27%; p < 0.02 vs HC). Monocyte-endothelial interaction was assessed by functional binding assay. When compared to normocholesterolemic rabbits, hypercholesterolemia led to a twofold increase in monocyte binding (74 +/- 13 vs 37 +/- 4 monocytoid cells per high power field (m/hpf); p < 0.03). The Ang II-antagonist and the PKC-antagonist led to a normalization of monocyte-endothelial binding (Ang II-antagonist: 37 +/- 9 m/hpf; PKC-antagonist: 41 +/- 17 m/hpf; p < 0.05). In conclusion, these results indicate that hypercholesterolemia activates the tissue renin angiotensin system, which results in an increased endothelial production of superoxide and monocyte adhesiveness. Ang II-antagonist inhibits free radical production and monocyte adhesion through a mechanism which may include PKC.     

Morphological changes of the triceps surae muscle-tendon unit during passive extension: an in vivo rabbit model

Objective. To elucidate the morphological and biomechanical manifestation of the triceps surae muscle-tendon unit during passive extension.

Design. The instantaneous changes within the load-deformation curve of muscle-tendon unit were analyzed by an in vivo rabbit model.

Background. Although muscle strains occur more frequently than complete failures, the failure mechanism of these sub-failure injuries is rarely investigated. Monitoring of the instantaneous changes in the load-deformation curve allows correlation with the morphological changes that occur during passive extension.

Methods. After anesthesia, the triceps surae muscle of rabbit was dissected and then stretched to failure by a MTS Bionix 858 machine. The morphological changes in failure patterns were recorded by photographs.

Results. The morphological and biomechanical manifestations of the triceps surae muscle-tendon unit was divided into five different portions: first, the viscoelastic portion with minimal morphologic change; second, the portion of micro-failure with local ecchymosis; third and fourth, the portions of macrofailure with sequential rupture of the muscle fibers; and fifth, the portion of rupture and separation of muscle parenchyma.

Conclusions. A threshold for stretch-induced injury does exist. The threshold of the initiation of micro-failure in this model was 16.5% of the strain, which corresponded to 16.6% of the maximal sustainable force.     

Biatrial substrate properties in patients with atrial fibrillation

Introduction: The atrial substrate plays an important role in the maintenance of atrial fibrillation (AF). Further investigation of the biatrial substrate may be helpful for understanding the mechanism of AF. The aim of this study was to investigate the properties of right and left atrial (RA and LA) substrate in AF patients and their impact on the catheter ablation.
Methods: Biatrial electroanatomic mapping using a three-dimensional mapping system (NavX) was performed in 117 consecutive patients with paroxysmal (n = 99) and persistent (n = 18) AF. The biatrial voltage and total activation time (TAT) were obtained during sinus rhythm.
Results: The LA had a lower voltage (1.6 ± 0.5 vs 2.0 ± 0.6 mV, P < 0.001) than the RA. The TAT correlated with the voltage (r =–0.65, P< 0.001). The patients with persistent AF had a lower atrial voltage, higher coefficient of variance for the LA voltage, longer LA TAT, and more extensive scar than those with paroxysmal. The patients with recurrent AF after catheter ablation had a lower LA voltage and higher incidence of LA scarring than those without recurrence. A scar located in the low anteroseptal or low posterior wall of LA was related to recurrence of AF. LA scarring was the independent predictor of AF recurrence after catheter ablation.
Conclusion: The LA voltage was lower than the RA, and the atrial voltage correlated with the TAT. Electroanatomical remodeling of the atria could be crucial to the maintenance of AF. The LA substrate properties may play an important role in the recurrence of AF after catheter ablation of AF.     

Latent membrane protein-1 of Epstein-Barr virus inhibits cell growth and induces sensitivity to cisplatin in nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) and the EBV encoded latent membrane protein-1 expression (LMP1) is commonly found in the tumour cells. LMP1 has been shown to be involved in modulation of cell growth in B cells but the biological properties of LMP1 expression in nasopharyngeal carcinoma cells are less defined. In this study, a full length LMP1 gene was introduced into an EBV negative nasopharyngeal carcinoma cell line, CNE2, and five LMP1-expressing clones were isolated. Expression of LMP1 did not confer cell growth advantage in CNE2 cells; instead, it induced growth inhibition both in vitro and in vivo. In addition, the LMP1 transfected cells were more susceptible to cisplatin-induced cell death and showed 1.4-4.0-fold increased sensitivity to cisplatin compared to the vector infected control clones. The effect of LMP1 on the balance of Bcl-2 and Bax ratio may play a role in inducing susceptibility to cisplatin-induced cell death. These results demonstrated that LMP1 did not confer growth advantage in CNE2 cells, suggesting that expression of LMP1 may not be crucial in sustaining cell growth in established cell lines. Alternatively, LMP1 alone may not be sufficient to facilitate nasopharyngeal carcinoma cell growth and additional oncogenic factors may be needed along with LMP1 in modulating the malignant property of nasopharyngeal carcinoma.