Human immune response against outer membrane proteins of Moraxella (Branhamella) catarrhalis determined by immunoblotting and enzyme immunoassay.

The role of Moraxella (Branhamella) catarrhalis as a respiratory tract pathogen is increasingly recognized. We looked at the human immune response against individual outer membrane proteins of M. catarrhalis and against the 81-kDa CopB protein, which has previously been shown to be a target for protective antibodies. Paired serum samples from six elderly patients with pneumonia were tested by Western blot (immunoblot) analysis by using outer membrane vesicles of M. catarrhalis 035E as antigen. All of the six convalescent-phase serum samples reacted with a protein which migrated at the position of the CopB protein and with a high-molecular-weight protein of M. catarrhalis; three serum samples also reacted with a 34-kDa outer membrane protein. Paired serum samples from 18 patients, 10 of which had M. catarrhalis infection on the basis of previous serology results, were tested by enzyme immunoassay (EIA) with the CopB protein and whole cells of M. catarrhalis 035E as antigens. Nine patients showed a significant rise in EIA titer between acute- and convalescent-phase sera when whole bacterial cells were used as antigens. Six (67%) patient samples that were positive by the EIA with the whole-cell antigen were also positive by the EIA with the CopB antigen, and six of nine patient samples negative by the EIA with the whole-cell antigen were also negative by the EIA with the CopB antigen. These results suggest that both the CopB and a high-molecular-weight protein are major targets of the immune response against M. catarrhalis, and further studies with greater amounts of patient materials are needed to elucidate the usefulness of CopB as an antigen in etiologic studies.     

Anatomic basis for use of a distal pedicle leg flap

Summary The cutaneous blood-supply of the limbs is ensured by three types of arteries: the large septo-cutaneous arteries, the slender musculocutaneous arteries, and the rare satellites of the cutaneous nerves. The skin cover of the outer aspect of the leg is particularly well vascularized thanks to its special situation, centered on the intermuscular septa bounding the outer compartment of the leg. Neuromuscular arteries are rare at this site, but there are numerous septo-cutaneous arteries at intervals along the septa. This anatomic study is based on 20 dissections and a radiologic survey and provides findings confirming the reliability of a distally based lateral leg flap. This pedicle arises from the fibular artery behind and the anterior tibial artery in front. It is situated, on average, 10.8 cm from the lateral malleolus, thus allowing coverage of peripheral losses of substances at the malleoli and heel.

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Bases anatomiques de l'utilisation d'un lambeau jambier à pédicule distal

Résumé La vascularisation cutanée des membres est assurée par trois types d'artères: les artères septocutanées qui sont volumineuses; les artères musculo-cutanées qui sont grêles et les artères superficielles, satellites du nerf à destinée cutanée, qui sont rares. Le revêtement cutané de la face latérale de la jambe est particulièrement bien vascularisé, grâce à sa situation privilégiée, centré sur les septa intermusculaires limitant la loge externe de la jambe. Les artères neuromusculaires sont rares à ce niveau. Par contre, on retrouve de nombreuses artères septo-cutanées volumineuses étagées le long des septa. Nous avons entrepris un travail anatomique reposant sur 20 dissections et sur une étude radiologique. Nos résultats nous permettent d'établir ces données et confirment la fiabilité d'un lambeau jambier latéral à pédicule distal. Ce pédicule naît de l'artère fibulaire en arrière et de l'artère tibiale antérieure en avant. Il est situé à 10,8 cm en moyenne de la malléole latérale permettant ainsi de couvrir les pertes de substance périphériques malléolaires et talonnières.

     

Neocortical substance P neurons in the baboon: an immunohistochemical finding

Substance P-like immunoreactive (SP-LI) neurons have been demonstrated, by an avidin-biotin immunohistochemical method, in several neocortical areas in the brains of baboons. These neurons are mostly small in size, and are of many different somatic shapes, including bipolar and multipolar types. They occur in laminae III-VI but are most common in laminae V and VI. It is postulated that these neurons could contribute to previously-described cortical SP-LI fiber networks.     

The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

Ayurveda is one of the ancient systems of health care of Indian origin. Roughly translated into "Knowledge of life", it is based on the use of natural herbs and herb products for therapeutic measures to boost physical, mental, social and spiritual harmony and improve quality of life. Although sheltered with long history and high trust, ayurveda principles have not entered laboratories and only a handful of studies have identified pure components and molecular pathways for its life-enhancing effects. In the post-genomic era, genome-wide functional screenings for targets for diseases is the most recent and practical approach. We illustrate here the merger of ayurveda and functional genomics in a systems biology scenario that reveals the pathway analysis of crude and active components and inspire ayurveda practice for health benefits, disease prevention and therapeutics.     

Redox regulation of p38 MAPK activation and expression of ICAM-1 and heme oxygenase-1 in human alveolar epithelial (A549) cells

We have explored the potential role of redox events in p38 mitogen-activated protein kinase (MAPK) activation and their relevance to the inducible expression of intercellular adhesion molecule-1 (ICAM-1) and heme oxygenase-1 (HO-1) in A549 cells. Tumor necrosis factor-alpha (TNFalpha) and hydrogen peroxide (H2O2) both activated p38, but only TNFalpha activated nuclear factor-kappaB (NF-kappaB). N-Acetyl-L-cysteine (20 mM) inhibited both H2O2- and TNFalpha-induced p38 phosphorylation (14 +/- 7 and 37 +/- 4% of control, respectively). The mitochondrial complex I and III inhibitors, rotenone and antimycin A, and allopurinol partially inhibited H2O2- but not TNFalpha-induced p38 activation. However, rotenone and antimycin A augmented intracellular oxidative stress measured by dichlorofluorescein fluorescence. TNFalpha, but not H2O2, induced ICAM-1 in A549 cells, which was attenuated by a proteasome inhibitor, but not by the p38 MAPK inhibitor SB203580. In contrast, hemin and hemoglobin, but neither TNFalpha nor H2O2, caused efficient HO-1 expression. However, hemin had no effect on p38 activation and SB203580 did not influence hemin-induced HO-1 protein expression. Collectively, these data suggest that p38 is a cytokine- and oxidative stress-responsive pathway in A549 cells. Whereas NF-kappaB appears crucial in ICAM-1 induction, p38 activation itself is not sufficient to confer HO-1 expression and may not be involved in HO-1 and ICAM-1 induction in A549 cells.     

Microdosimetric measurements of radiation quality variations in homogeneous phantoms irradiated by fast neutron beams

The Dual Radiation Action Theory of Kellerer and Rossi (DRA), along with presently available microdosimetric techniques, is applied to the determination of radiation quality variation within tissue equivalent phantoms irradiated by collimated fast neutron beams. The neutron beams investigated were produced by the bombardment of 22.5 and 16 MeV d + on beryllium and by the T(d,n)4He reaction (15-MeV neutrons). Microdosimetric spectra were obtained at points of varying depth and lateral distance from the central axis within a tissue equivalent phantom, including points within the penumbra. From the microdosimetric spectra the parameter RQ, a first approximation to RBE derived from DRA theory, is calculated for each point. All RQ values are calculated for the same level of effect. For these three different beams the results show that the RQ values for the total radiation spectrum of neutron and gamma radiation remain fairly constant with depth and with lateral distance from the beam axis at 2 and 10 cm depths. The largest central axis variation in RQ is 8% for the d(16) + Be beam. The largest variation between a penumbra and an on-axis RQ value is 4% at 2 cm depth in the d(22.5) + Be beam. The results for the d (22.5) + Be beam disagree with previously reported radiological results while the 15 McV beam results are in good agreement.     

BRAF mutations in aberrant crypt foci and hyperplastic polyposis

Patients with hyperplastic polyposis have multiple hyperplastic polyps (HPs) and increased risk of colorectal carcinomas. Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesions in colorectal carcinogenesis. We evaluated BRAF mutations by DNA sequencing in 53 ACF from patients with sporadic colorectal carcinomas and familial adenomatous polyposis, in 18 sporadic HPs from patients with resected colorectal cancer, and in 70 HPs, 4 serrated adenomas, 3 admixed hyperplastic-adenomatous polyps, 10 tubular adenomas, and 6 carcinomas from 17 patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status was compared with clinicopathological features and other genetic alterations by marginal logistic regression. BRAF mutation was present in only 2% of ACF and 6% of sporadic HPs. In contrast, BRAF mutation was present in 43% of HPs (P = 0.01 versus sporadic HPs), 75% of serrated adenomas, 33% of admixed hyperplastic-adenomatous polyps, 30% of tubular adenomas, and 33% of carcinomas from patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status in patients with multiple/large HPs and/or hyperplastic polyposis correlated with HPs from the same patient (odds ratio, 5.8; P = 0.0002) but associated with younger age (odds ratio, 0.83; P = 0.006 compared to older age), with a large HP (odds ratio, 22.5; P = 0.01 compared with patients with multiple HPs), with location of HPs in the right colon (odds ratio, 3.0; P = 0.03), and with methylation of the p16 gene and the MINT31 locus [odds ratio, 12.2 (P = 0.0001) and 4.4 (P = 0.02), respectively]. Our study shows that BRAF mutation status is heterogeneous among patients with multiple/large HPs and/or hyperplastic polyposis, suggesting differences in pathogenesis of HPs that indicate subsets within this phenotype.     

A sea urchin gene encoding dystrophin-related proteins

The gene which is defective in Duchenne muscular dystrophy (DMD) is the largest known gene. The product of the gene in muscle, dystrophin, is a 427 kDa protein. The same gene encodes at least six additional products: two non-muscle dystrophin isoforms transcribed from promoters located in the 5'-end region of the gene and four smaller proteins transcribed from internal promoters located further downstream. Several other genes, encoding evolutionarily related proteins, have been identified. These include a structurally very similar gene in vertebrates encoding utrophin (DRP1), which is closely related to dystrophin, and a number of small and simple genes in vertebrates or invertebrates encoding proteins similar to some of the small products of the DMD gene. We have isolated a sea urchin gene showing very strong sequence and structural homology with the DMD and utrophin genes. Sequence and intron/exon structure similarities suggest that this gene is related to a precursor of both the DMD gene and the gene encoding utrophin. The sea urchin gene has the unique complex structure of the DMD gene. There is at least one, and possibly more, product(s) transcribed from internal promoters, as well as a large product of >300 kDa containing at least three of the four major domains of dystrophin. The small product seems to be evolutionarily related to Dp116, one of the small products of the human DMD gene. Partial characterization of this gene helped us to construct an evolutionary tree connecting the vertebrate dystrophin gene family with related genes in invertebrates. The constructed evolutionary tree also implies that the vertebrate small and simple structured gene encoding a Dp71-like protein, called DRP2 , evolved from the dystrophin/utrophin ancestral large and complex gene by a duplication of only a small part of the gene.