Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer

Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738–0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC.     

Lipopolysaccharide and serum cause the translocation of G-protein to the membrane and prime neutrophils via CD14.

Lipopolysaccharide (LPS) in combination with human serum, in the absence of a second stimulus, causes an increase in the amount of the alpha -subunit (Gi alpha 2) of the guanine nucleotide binding protein Gi2 associated with the membrane. The LPS-serum complex also primes human neutrophils for O2- production in response to stimulation by the chemotactic factor fMet-Leu-Phe. Added serum factor is essential for priming at low concentrations of LPS. In the presence of serum, significant potentiation can be observed at LPS concentration as low as 0.1 ng/ml. The priming is dose and time dependent. Furthermore, the observed actions of the LPS-serum complex are not reversible since they cannot be overcome by washing. Monoclonal antibody against CD14 inhibits both the direct and priming actions of the LPS-serum complex. On the other hand, neither the antibody against CD11b nor the antibody against TNF-alpha inhibits the action of this complex.     

Identification des cercaires de Schistosoma africains émises par Bulinus umbilicatus,B. truncatus et B. forskalii

Résumé Trois indices chétotaxiques AD, AL et U, des cercaires de quatre espèces pré-identifiées de Schistosoma africains, émises par des Mollusques infestés naturellement ou expérimentalement, ont été calculés. AD et AL correspondant respectivement à la distance relative entre les papilles dorsales et les papilles latérales. U correspond au nombre total des papilles du tronc caudal. La simple comparaison des moyennes arithmétiques d'un ou deux de ces trois indices permet de distinguer les cercaires de Schistosoma haematobium et de S. curassoni émises par Bulinus umbilicatus; les cercaires de S. haematobium et S. bovis émises par B. truncatus; les cercaires de S. bovis et S. intercalatum émises par B. forskalii.

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Identification des cercaires de Schistosoma africains émises par Bulinus umbilicatus, B. truncatus et B. forskalii

Three chaetotaxic indices, AD, AL and U, of cercariae of four pre-identified African Schistosoma species, obtained from natural or experimental infections, were established. AD and AL correspond respectively to the relative distance between the dorsal and lateral papillae. U corresponds to the total number of tail stem papillae. The simple comparison of average values of one or two of these three indices facilitated identification of the cercariae of Schistosoma haematobium and S. curassoni emitted by Bulinus umbilicatus, cercariae of S. haematobium and S. bovis shed by B. truncatus, and cercariae of S. bovis and S. intercalatum emitted by B. forskalii.

     

The genetics of chemotaxis in Drosophila melanogaster: Selection for repellent insensitivity

Summary In a Y-unit maze wild-type flies of Drosophila melanogaster were tested for their chemotactic behavior reactions to insect repellents. Selection over 12 generations in two parallel experiments yielded two insensitive lines. Crosses indicated that the genes that were responsible for insensitivity were at least in part dominant. Lines selected for insensitivity to one repellent were also insensitive to a second repellent.     

Membrane dynamics of lymphocyte interaction with antigen and tolerogen.

The principle of hapten-specific carrier-dependent immunologic tolerance was used to study the in vivo and in vitro interaction of lymphocyte membrane receptors with antigen (DNP-KLH) and tolerogen (DNP-MGG). Direct fluorescent techniques were employed to illustrate the binding of tolerogeu and antigen to the same population of lymphoid cells and the subsequent in vivo and in vitro events related to capping and regeneration of membrane receptors.     

A series of mutable alleles of the white locus in Drosophila melanogaster

Summary The origin and phenotypes of a number of zeste mutant stocks with mutable white loci are described. Each newly arising form was lighter in eye color than the mutant it originated from. In each case the lighter pigmentation is believed to be due to an increase in genetic material in the proximal region of the white locus, the increase supposedly being the result of unequal crossing over. Some of the mutations which arose in the mutable stocks are reversions. They occurred in males as well as in homo- and heterozygous females. The reversions are believed to be due to a decrease in genetic material in the proximal region of the white locus. The decrease is assumed to be the result of intrachromosomal recombination. At least some of these events took place premeiotically. New mutants which originate frequently from mutable stocks are stable. In addition to the structure of the mutable white locus there is probably at least one still unknown factor which affects its mutability since the frequency of mutations arising in the mutable stocks decreases over the years.     

Analysis,classification, and coding of multielectrode spike trains with hidden Markov models

It is shown that hidden Markov models (HMMs) are a powerful tool in the analysis of multielectrode data. This is demonstrated for a 30-electrode measurement of neuronal spike activity in the monkey's visual cortex during the application of different visual stimuli. HMMs with optimized parameters code the information contained in the spatiotemporal discharge patterns as a probabilistic function of a Markov process and thus provide abstract dynamical models of the pattern-generating process. We compare HMMs obtained from vector-quantized data with models in which parametrized output processes such as multivariate Poisson or binomial distributions are assumed. In the latter cases the visual stimuli are recognized at rates of more than 90% from the neuronal spike patterns. An analysis of the models obtained reveals important aspects of the coding of information in the brain. For example, we identify relevant time scales and characterize the degree and nature of the spatiotemporal variations on these scales.