Effect of venous air embolization on pulmonary microvascular protein permeability

OBJECTIVE: An increase in pulmonary lymph flow and lymph protein clearance following pulmonary air embolization has been interpreted as evidence of increased pulmonary microvascular permeability. The authors hypothesized that air embolization does not alter the pulmonary microvascular permeability to protein and that this could be demonstrated by determining the effect of air embolization on the pulmonary solvent drag reflection coefficient (sigma(f)). METHODS: Anesthetized dogs were instrumented with left atrial balloon-tipped catheters, pulmonary lymphatic cannulae, and inferior vena caval catheters. Values were determined for pulmonary lymph flow (Q(L)) and the lymph-to-plasma protein concentration ratio (C(L)/C(P)) at baseline, after C(L)/C(P) was decreased to a filtration independent value by raising left atrial pressure via progressive balloon inflation and after 2 h of air embolization into the inferior vena cava with continued left atrial hypertension. RESULTS: Q(L) increased and C(L)/C(P) decreased to a filtration-independent value following induction of left atrial hypertension. Air embolization induced during left atrial hypertension resulted in no significant change in C(L)/C(P). The authors were unable to demonstrate that sigma(f) changed following pulmonary air embolization. CONCLUSIONS: Utilizing the washdown technique, the authors could not find any evidence that pulmonary microvascular protein permeability is altered by air embolization.     

Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology

Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid beta (Abeta) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (DeltaTau) by executioner caspases. Following caspase-cleavage, DeltaTau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. DeltaTau can be phosphorylated by glycogen synthase kinase-3beta and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, DeltaTau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, DeltaTau colocalizes with Abeta(1-42) and is induced by Abeta(1-42) in vitro. Collectively, our data imply that Abeta accumulation triggers caspase activation, leading to caspase-cleavage of tau, and that this is an early event that may precede hyperphosphorylation in the evolution of AD tangle pathology. These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.     

Nipple (papilla) development in puberty: longitudinal observations in girls

The purpose of this study was to determine the manner of breast nipple (papilla) development occurring during puberty in girls on a longitudinal basis and to compare this development to the established criteria of sexual maturation. Forty-six girls (19 white and 27 black) were followed for periods of 2 to 5 years (mean 2.67 years). In each, the nipple diameter was measured and the Tanner stage assessed. Minimal nipple development occurred from stages PH1 to PH3 (3.24 to 4.44 mm) and B1 to B3 (3.00 to 4.72 mm) or more than 1 year prior to menarche (3.75 mm). Significant growth occurred beyond stages PH3 (PH4 6.54 mm, PH5 8.98 mm) and B3 (B4 7.25 mm, B5 9.41 mm) and from less than 1 year prior to menarche to more than 1 year after menarche (5.92 mm for girls less than 1 year premenarche, 7.88 mm for girls in their first year after menarche, and 9.05 mm for girls more than 1 year beyond menarche). A more objective definition for breast stages B4 and B5, based upon nipple diameter, is now feasible. Thus, these data enhance the precision with which physiologic events occurring toward the close of puberty in girls can be studied.     

An animal model of acute otitis media consequent to beta-lactamase-producing nontypable Haemophilus influenzae.

A chinchilla model of acute otitis media with effusion consequent to beta-lactamase-producing nontypable Haemophilus influenzae was developed using the method of direct inoculation of 145 colony-forming units (CFU) or 252 CFU of beta-lactamase-producing nontypable H influenzae into the right superior bullae of 40 chinchillas. The course of the disease was documented longitudinally by otomicroscopy, tympanometry, and periodic culturing of the middle ears. Onset of the disease occurred in 100% of the animals between two and six days postinoculation and resolution was complete in all ears by day 36. Results of rechallenge with the same organism support the combined effect of a local and weaker systemic middle ear protective mechanism rendering resistance to reinfection with a homologous organism in the chinchilla.     

Potential errors in the laboratory diagnosis of paroxysmal nocturnal hemoglobinuria

In a retrospective study of laboratory tests for paroxysmal nocturnal hemoglobinuria (PNH), the red blood cells of several patients gave conflicting results when different testing procedures were used. To resolve these discrepancies, an examination of the various procedures was undertaken, using sulfhydryl reagent-treated red blood cells as model PNH cells. Rabbit antiserum to human red blood cells was used to sensitize erythrocytes for specific antibody-dependent complement lysis sensitivity tests. Acidified serum and inulin were used in fluid-phase complement activation tests. For the general laboratory, a modification of the sucrose lysis test is described, which can give the relative complement sensitivity and size of an abnormal subpopulation of red blood cells. Considering the results of our patients and the reports in the literature of the association of PNH with a variety of lymphoproliferative and myeloproliferative disorders, it is stressed that testing procedures for PNH be controlled more carefully for a better understanding of the nature of the membrane defect.     

Streptococcus mutans-like bacteria from human dental plaque in a Sri Lanka (Ceylon) population

Abstract – This paper reports on the presence of low numbers of Streptococcus mutans among the oral streptococci present in human dental plaque in a Sri Lanka (Ceylon) population, where the caries activity is low and a low sucrose intake is combined with the presence of heavy plaque deposits. Plaque samples of unknown age were collected from 10 individuals in a tea estate, and another 10 samples were collected from dental students 19 days following interruption of oral hygiene. Of 670 such strains of oral streptococci studied, none showed typical "frosted glass" colony morphology on Mitis Salivarius agar. However, when subjected to physiological tests 14 of them were classified as S. mutans.     

炎症在启动和维持心房颤动中的地位——对研究资料的系统回顾

近年的研究显示,炎症在启动、维持心房颤动(房颤)中起非常重要的作用.美国Issac等对1995～2007年间以英文发表的有关房颤与炎症关系方面的文章,以及药物,如他汀类、血管紧张素转化酶抑制剂(ACEI)及糖皮质激素在治疗房颤中的作用方面的文章进行了系统回顾(J Am Coll Cardiol,2007, 50:2021-2028).     

Apolipoprotein E pathology in vascular dementia

Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles (NFTs), blood vessels, and reactive astrocytes. Labeling occurred in VaD cases that had confirmed APOE genotypes of 3/3, 3/4, and 4/4, with respect to NFTs, staining of the nApoECF co-localized with PHF-1 and was predominantly localized to large, stellate neurons in layer II of the entorhinal cortex. Quantitative analysis indicated that approximately 38.4% of all identified NFTs contained the amino-terminal fragment of apoE. Collectively, these data support a role for the proteolytic cleavage of apoE in the VaD and support previous reports that APOE polymorphism is significantly associated with susceptibility in this disease.