The mannose receptor mediates uptake of pathogenic and nonpathogenic mycobacteria and bypasses bactericidal responses in human macrophages

The mannose receptor (MR) is involved in the phagocytosis of pathogenic microorganisms. Here we investigated its role in the bactericidal functions of human monocyte-derived macrophages (MDMs), using (i) trimannoside-bovine serum albumin (BSA)-coated latex beads and zymosan as particulate ligands of the MR, and (ii) mannan and mannose-BSA as soluble ligands. We show that phagocytosis of mannosylated latex beads did not elicit the production of O2-. Zymosan, which is composed of alpha-mannan and beta-glucan, was internalized by the MR and a beta-glucan receptor, but the production of O2- was triggered only by phagocytosis through the beta-glucan receptor. Activation and translocation of Hck, a Src family tyrosine kinase located on lysosomes, has previously been used as a marker of fusion between lysosomes and phagosomes in human neutrophils. In MDMs, Hck was activated and recruited to phagosomes containing zymosan later than LAMP-1 and CD63. Phagosomes containing mannosylated latex beads fused with LAMP-1 and CD63 vesicles but not with the Hck compartment, and the kinase was not activated. We also demonstrate that the MR was unable to distinguish between nonpathogenic and pathogenic mycobacteria, as they were internalized at similar rates by this receptor, indicating that this route of entry cannot be considered as a differential determinant of the intracellular fate of mycobacteria. In conclusion, MR-dependent phagocytosis is coupled neither to the activation of NADPH oxidase nor to the maturation of phagosomes until fusion with the Hck compartment and therefore constitutes a safe portal of entry for microorganisms.     

Skin diseases in Bamako (Mali)

BACKGROUND: Skin diseases have only recently been considered as a possible public health problem in developing countries. Data supporting this matter are scarce. The aim of this study is to report the experience of a specialized dermatologic center in Bamako (Mali) in order to complete two previous studies conducted in the Bamako area: a prevalence study in the general population and a study in nonspecialized health centers of Bamako. It is our intention to provide a comprehensive picture of the problem of skin diseases in an African developing country. METHODS: We retrospectively collected all cases of skin diseases diagnosed during consultations provided at the Institut Marchoux in Bamako, the only center specializing in dermatology in Mali, during the year 1993. RESULTS: A total of 10,575 new outpatients were seen with 10,889 skin diseases. The main skin diseases registered were as follows: infectious dermatoses (41% of all diagnoses, including scabies (16.6%), superficial mycoses (13.6%), and primary pyoderma (5.6%)), dermatitis (20.4%), papular urticaria (4.4%), acne (4.2%), pityriasis alba (3.6%), keratoderma (3.6%), and urticaria (3%). Typical tropical infectious diseases accounted for only 1% of all diagnoses. CONCLUSIONS: It appears that certain skin diseases (mainly scabies and pyoderma) are an important health problem for the population of the Bamako area. Public health policies should be implemented in order to manage this problem rationally.     

Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome

Abnormal responsiveness of adrenocortical cells to gastric inhibitory polypeptide (GIP) in food-dependent Cushing's syndrome suggested that adrenal expression of ectopic, overexpressed, or mutated GIP receptor (GIPR) underlies this syndrome. The expression of GIPR was studied by RT-PCR in human adrenal tissues from two patients with GIP-dependent Cushing's syndrome (adenoma, bilateral hyperplasia), five fetal or adult controls, one patient with Cushing's disease, and four patients with non-food-dependent cortisol-secreting adenomas or bilateral hyperplasias and compared to that in normal pancreas. Hybridization of the RT-PCR-amplified ribonucleic acids with the human GIPR complementary DNA showed an overexpression of GIPR in the adrenals of the two GIP-dependent Cushing's syndrome patients compared to that in normal adrenal tissues (2-3 orders of magnitude) or pancreas (10-fold); no signal could be seen in adrenal adenomas or macronodular hyperplasia from cases of non-food-dependent Cushing's syndrome. No mutation of the GIPR was identified by sequencing the full-length receptor in GIP-dependent adrenal tissue. New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues. Incubation of adrenal cells with GIP stimulates cortisol secretion in GIP-dependent, but not in normal fetal, adult, or non-food-dependent Cushing's syndrome, adrenals. We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome.     

Expression of NADPH oxidase is induced by all-trans retinoic acid but not by phorbol myristate acetate and 1,25 dihydroxyvitamin D3 in the human promyelocytic cell line NB4

Human promyelocytic cells, NB4, differentiate into neutrophils in response to all-trans retinoic acid (ATRA). It has recently been proposed that NB4 cells have bilineage potential because these cells are also able to differentiate into monocyte/macrophages when exposed to a combination of 1,25-dihydroxyvitamin D3 (VD3) and phorbol myristate acetate (PMA). Differentiation of myeloid cells into neutrophils or monocytes is associated with the acquisition of the O2- producing enzyme, NADPH oxidase, which plays a critical role in microbial killing. In this study, the expression of the components of the NADPH oxidase complex during the differentiation of NB4 cells into neutrophils or macrophages has been investigated. Whereas cells exposed to ATRA were able to produce O2- after 2 days of differentiation, they remain unable to generate O2- when exposed to PMA or PMA + VD3. With the exception of p21rac, none of the other oxidase components was expressed in non-differentiated cells. Addition of ATRA induced the progressive expression and accumulation of p22phox, p91phox, p47phox and p67phox. Compared to the other components, p67phox was expressed late and its expression appeared to correlate most closely with the generation of O2- in the differentiation process. In PMA or PMA + VD3-differentiated NB4 cells, expression of the NADPH oxidase components was incomplete. Therefore, ATRA induced the expression of a functional NADPH oxidase complex in neutrophil-like NB4 cells. In contrast, when NB4 cells are exposed to monocytic differentiating agents, they acquire only part of the phenotypic characteristics of monocytes and lack one of the major phagocytic functionalities, the respiratory burst oxidase.     

Locking and Unlocking the Molecular Spin Crossover Transition

The Fe(II) spin crossover complex [Fe{H₂B(pz)₂}₂(bipy)] (pz = pyrazol‐1‐yl, bipy = 2,2′‐bipyridine) can be locked in a largely low‐spin‐state configuration over a temperature range that includes temperatures well above the thermal spin crossover temperature of 160 K. This locking of the spin state is achieved for nanometer thin films of this complex in two distinct ways: through substrate interactions with dielectric substrates such as SiO₂ and Al₂O₃, or in powder samples by mixing with the strongly dipolar zwitterionic p ‐benzoquinonemonoimine C₆H₂(—? NH₂)₂(—? O)₂. Remarkably, it is found in both cases that incident X‐ray fluences then restore the [Fe{H₂B(pz)₂}₂(bipy)] moiety to an electronic state characteristic of the high spin state at temperatures of 200 K to above room temperature; that is, well above the spin crossover transition temperature for the pristine powder, and well above the temperatures characteristic of light‐ or X‐ray‐induced excited‐spin‐state trapping. Heating slightly above room temperature allows the initial locked state to be restored. These findings, supported by theory, show how the spin crossover transition can be manipulated reversibly around room temperature by appropriate design of the electrostatic and chemical environment.     

Genomic study of hemagglutinins of swine influenza (H1N1) viruses associated with acute and chronic respiratory diseases in pigs

The nucleotide sequences of HA1 domain of hemagglutinin of clinical H1N1 influenza viruses, isolated during recent outbreaks of respiratory problems in pig farms of Quebec, was determined. The viruses A/Sw/Quebec/3291/90 (SwQc3291) and A/Sw/Quebec/1747/90 (SwQc1747), associated with chronic respiratory disease, showed close similarity for their deduced aa sequences. When compared with the published data of A/Sw/Quebec/5393/91 (SwQc91), the variations observed included Cb and Ca antigenic sites in SwQc3291 and Sb and Ca sites in SwQc1747 isolates. These variants were antigenically related to SwQc91 virus associated with chronic respiratory disease, but differed from the more classical A/Sw/Quebec/192/81 (SwQc81) strain. In contrast, A/Sw/Quebec/1192/86 (SwQc1192) isolate, associated with acute respiratory influenza, showed maximum number of differences including Ca, Cb, Sa and Sb antigenic sites. The latter, as well as the SwQc81 strain, were antigenically distinct from SwQc91 virus on the basis of its cross-reactivity to MAbs directed against the HA glycoprotein. Estimation of genetic distances and phylogenic tree analysis showed that SwQc1747 and SwQc3291 were closely related, but these viruses along with SwQc1192 were considerably divergent from SwQc91 virus.     

Structural coherency of graphene on Ir(111)

Low-pressure chemical vapor deposition allows one to grow high structural quality monolayer graphene on Ir(111). Using scanning tunneling microscopy, we show that graphene prepared this way exhibits remarkably large-scale continuity of its carbon rows over terraces and step edges. The graphene layer contains only a very low density of defects. These are zero-dimensional defects, edge dislocation cores consisting of heptagon-pentagon pairs of carbon atom rings, which we relate to small-angle in-plane tilt boundaries in the graphene. We quantitatively examined the bending of graphene across Ir step edges. The corresponding radius of curvature compares to typical radii of thin single-wall carbon nanotubes.