Does chronic hypoxaemia induce transformations of fibre types?

The study comprised nine patients with chronic obstructive lung disease. Quadriceps muscle biopsies were studied with respect to fibre type composition before and after haemodilution that brought haemoglobin (Hb) to within normal limits. Ten days elapsed between the two biopsy occasions. The arterial oxygen tension (PaO2) and saturation (SaO2) were depressed to 8.4 +/- 2.0 kPa and 89 +/- 11% in the patients with chronic obstructive lung disease and increased to 9.2 +/- 2.1 and 91 +/- 8% with haemodilation. The type II fibre proportion was 71 +/- 12% before haemodilation and significantly higher than normal (reference group, see Aniansson et al. 1981). Following haemodilation the proportion of type II fibres decreased significantly to 60 +/- 14%. The proportion of type II fibres was directly related to the haemoglobin content before, but not after, haemodilation and was inversely related to PaO2 and SaO2 both before and after haemodilation. In conclusion, hypoxaemia may be a factor underlying the high proportion of type II fibres found in patients with chronic obstructive lung disease.     

FN-C1q and C1 INH C1r-C1s complexes as indicators of complement activation in patients with chronic lymphocytic leukaemia

We have previously found low levels of C1 and C4 INH in the sera of chronic lymphocytic leukaemia (CLL) patients. Hypocomplementaemia was supposed to be the consequence of a permanent activation of the classical pathway. We have compared the levels of C1 INH-C1rC1s and C1q-FN complexes in the sera of 95 CLL patients and 100 healthy controls, because these complexes are known to be formed in the early stage of classical pathway activation. A significant increase in the level of both types of complexes was found in sera of CLL patients as compared to the controls. These findings support the assumption that the classical complement pathway is activated in the patients with CLL.     

Molecular and functional characterization of a mutant allele of the mitogen-activated protein-kinase geneSLT2(MPK1) rescued from yeast autolytic mutants

 We have further characterized the functionality of the Saccharomyces cerevisiae gene SLT2(MPK1), coding for a MAP-kinase homolog essential for cell integrity, which is involved in the Pkc1p signalling pathway. This gene was isolated on the basis of its capacity to complement the thermosensitive-autolytic, osmotic-remediable phenotype of lyt2 mutants. Both slt2Δ and lyt2 mutants displayed a caffeine-sensitive phenotype consisting of cell lysis that was not dependent on temperature. Caffeine concentrations affecting the growth of these mutant strains were dependent on the genetic background, the SSD1 allele being very significant in this regard. The SLT2 allele of several lyt2 strains was both rescued and amplified by PCR. The recovered allele was shown to be non-functional as it could not complement the lytic phenotype of both deletion (slt2Δ) and lyt2 strains. After nucleotide sequencing of the recovered allele, we found that the defect of lyt2 mutants consists in a substitution of an aspartic acid for a glycine at position 35 of the amino-acid sequence of Slt2p. Gly35 is the third glycine of a glycine cluster (Gly-X-Gly-X-X-Gly), a conserved region in protein kinases and other nucleotide-binding proteins. Received: 13 October/27 November 1995     

Histamine-releasing properties of guinea pig cardiac mast cells

The immunization of guinea pigs with OA + Al(OH)3 induced substantial IgG1a and IgG1b antibody response and low, transient IgE response, as examined by PCA test. Cardiac mast cells obtained by enzymatic dispersion method from sensitized animals released histamine in vitro after the challenge with specific antigen (histamine release up to 21%). Cardiac mast cells obtained from nonsensitized guinea pigs were sensitive to the action of ionophore A23187 and polymyxin B only when the agents were used in high concentrations (histamine release up to 25.1% and 21. respectively) and were only slightly responsive to the challenge with Concanavalin A and compound 48/80.     

Expression of the proteoglycans versican and mel-CSPG in dysplastic nevi

Nevi with architectural disorder and cytologic atypia of melanocytes (NAD) (also called dysplastic nevi) have been controversial with regard to their relationship with melanoma risk and to their gradation in 3 degrees of atypia. Versican and the melanoma-associated proteoglycan (mel-CSPG) are 2 major proteoglycans expressed by malignant melanoma, and they have a role in the regulation of cell adhesion, migration, and differentiation. We evaluated the differences in versican and mel-CSPG expression in nevi, NAD with several degrees of atypia, and primary malignant melanoma. Immunoreactivity for versican was negative in benign melanocytic nevi, positive in NAD (ranging from weakly to intensely positive), and intensely positive in malignant melanoma. Immunostaining for mel-CSPG was negative in benign melanocytic nevi and mild to moderately positive in NAD and melanoma. Our results suggest that versican expression may be of value for distinguishing NAD from benign melanocytic nevi and for distinguishing severe NAD from mild and moderate NAD.     

Bacterial DNA activates human neutrophils by a CpG-independent pathway

Bacterial DNA stimulates macrophages, monocytes, B lymphocytes, NK cells, and dendritic cells in a CpG-dependent manner. In this work we demonstrate that bacterial DNA, but not mammalian DNA, induces human neutrophil activation as assessed by L-selectin shedding, CD11b upregulation, and stimulation of cellular shape change, IL-8 secretion, and cell migration. Induction of these responses is not dependent on the presence of unmethylated CpG motifs, as neutrophil stimulatory properties were neither modified by CpG-methylation of bacterial DNA nor reproduced by oligonucleotides bearing CpG motifs. We found that human neutrophils express Toll-like receptor (TLR) 9 mRNA. However, as expected for a CpG-independent mechanism, activation does not involve a TLR9-dependent signaling pathway; neutrophil stimulation was not prevented by immobilization of bacterial DNA or by wortmannin or chloroquine, two agents that inhibit TLR9 signaling. Of note, both single-stranded and double-stranded DNA were able to induce activation, suggesting that neutrophils might be activated by bacterial DNA at inflammatory foci even in the absence of conditions required to induce DNA denaturation. Our findings provide the first evidence that neutrophils might be alerted to the presence of invading bacteria through recognition of its DNA via a novel mechanism not involving CpG motifs.     

Y Chromosome and Mitochondrial DNA Characterization of Pasiegos, a Human Isolate from Cantabria (Spain)

Mitochondrial DNA sequences and Y chromosome haplotypes were characterized in Pasiegos, a human isolate from Cantabria, and compared with those of other Cantabrian and neighbouring Northern Spain populations. Cantabria appears to be a genetically heterogeneous community. Whereas Lebaniegos do not differ from their eastern Basque and western Asturian and Galician neighbours, Pasiegos and other non‐Lebaniego Cantabrians show significant differences with all of them. Pasiegos are peculiar for their high frequencies of Y chromosomal markers (E‐M81) with North African assignation, and Y chromosomal (R‐SRY2627) and mtDNA (V, I, U5) markers related to northern European populations. This dual geographic contribution is more in agreement with the complex demographic history of this isolate, as opposed to recent drift effects. The high incidence in Cantabrians with pre‐V and V mtDNA haplotypes, considered as a signal of Postglacial recolonization in Europe from south‐western refugees, points to such refugees as a better candidate population than Basques for this expansion. However, this does not discount a conjoint recolonization.     

Small-scale field trial of a sensing device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in northwestern Argentina

Two prototypes of sensing devices for detecting peridomestic populations of Triatoma infestans Klug were tested in paired trials with bamboo canes in Amamá and nearby rural villages under triatomine surveillance. In infested peridomestic structures housing domestic animals, 1-2 pairs of numbered devices were placed per test site, left for 3-9 nights, and inspected for evidence of infestation. Prototype A was a black plastic cylinder 19 cm high and 10 cm diameter, with a screw cap on the top, 2 openings in the bottom, and a removable central structure made of resistant plastic coated with leather. Prototype B had square leather pieces rolled into cylinders instead of the central structure. Prototype A was significantly more sensitive than the bamboo cane with pleated paper inside in 13 test sites in which 20 pairs were tried. In a smaller series involving 7 pairs, prototype B also detected infestations more frequently than the cane. Triatomine feces were the signs most frequently recorded by both prototypes, whereas the bamboo canes recorded no feces. Ten T. infestans and 1 Triatoma guasayana Wygodzinsky & Avalos were collected from the prototypes placed on the ground or walls, not beneath the thatched roofs of the animal shelters, whereas only 3 T. infestans were collected from the canes. This study describes an effective sensing device for detecting T. infestans populations in outdoor animal shelters and provides quantitative field data on its performance.     

Cimetidine and placebo-cimetidine in the treatment of patients with chronic gastric ulcer (a multiclinical randomized double-blind comparative study)

The efficacy of a 4-week cimetidine treatment was examined by a double-blind randomized study in 37 outpatients with endoscopically verified chronic gastric ulcer. The patients received a daily dose of 3 times 1 tablet and, at night before going to bed 2 more tablet, thus a total amount of 1 g cimetidine, or cimetidine-placebo, but in case of complaints they could take in addition a mixed alkaline powder. Patients not recovering in response to a 4-week treatment, were then administered daily 5 tablets of cimetidine up to their complete recovery. Endoscopic, laboratory and clinical examinations were carried out every other week. As a result of a 4-week treatment, 56% of the cimetidine group recovered. The difference was not significant (P less than 0.2). The size of the ulcer and the intensity of the complaints were reduced significantly in both groups. The decrease in the size of the ulcer was significantly greater in the first two weeks of cimetidine treatment than in the cimetidine-placebo group (P less than 0.05). This favourable dynamics of ulcer healing was not felt in the second two weeks of treatment, and after four weeks there was no difference in the size of the residual ulcer to between the two groups. Cimetidine seemed to be a suitable drug for treating chronic gastric ulcer, since its healing rate proved to be better than that of placebo, the gain in weight also was favourable and there were no side-effects.