Lactate and epinephrine during exercise in altitude natives

Kayser, Bengt, Roland Favier, Guido Ferretti, DominiqueDesplanches, Hilde Spielvogel, Harry Koubi, Brigitte Sempore, and HansHoppeler. Lactate and epinephrine during exercise in altitudenatives. J. Appl. Physiol. 81(6):2488-2494, 1996.We tested the hypothesis that the reported lowblood lactate accumulation ([La]) during exercise inaltitude-native humans is refractory to hypoxia-normoxia transitions byinvestigating whether acute changes in inspiredO₂ fraction(FI_O2) affect the[La] vs. power output ()relationship or, alternatively, as reported for lowlanders, whetherchanges in [La] vs. on changes inFI_O2 are related tochanges in blood epinephrine concentration ([Epi]). Altitude natives [n = 8, age 24 ± 1 (SE) yr, body mass 62 ± 3 kg, height 167 ± 2 cm]in La Paz, Bolivia (3,600 m) performed incremental exercise with twolegs and one leg in chronic hypoxia and acute normoxia (AN). Submaximalone- and two-leg O₂ uptake (O₂) vs. relationships were not altered byFI_O2. AN increased two-legpeak O₂ by 10% and peak by 7%. AN paradoxically decreasedone-leg peak O₂ by 7%,whereas peak remained the same. The[La] vs. relationships were similar tothose reported in unacclimatized lowlanders. There was a shift to theright on AN, and maximum [La] was reduced by 7 and 8% forone- and two-leg exercises, respectively. [Epi] and[La] were tightly related (mean r = 0.81) independently ofFI_O2. Thus normoxiaattenuated the increment in both [La] and [Epi]as a function of , whereas the correlation between[La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitudenatives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes inFI_O2 on [La] during exercise.

     

Characterization of Nine Novel Mutations in the CD40 Ligand Gene in Patients with X-Linked Hyper IgM Syndrome of Various Ancestry

X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by defective expression of the CD40 ligand (CD40L) by activated T lymphocytes, resulting in inefficient T-B cell cooperation and failure of B cells to undergo immunoglobulin isotype switch. In the present work, we describe nine patients of various ancestry who bear different mutations in the X chromosome–specific CD40L gene. Two of the mutations were nonsense mutations, one each resulting in premature stop codons at amino acid residues 39 and 140. Three patients had single point missense mutations, one each at codons 126, 140, and 144. Another patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and premature termination. Three patients showed insertions, one each of 1, 2, and 4 nt, probably because of polymerase slippage, resulting in frameshift mutation and premature termination. Overall, these observations confirm the heterogeneity of mutations in HIGMX-1. However, the identification of two patients whose mutation involves codon 140 (previously shown to be altered in two other unrelated subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two additional patients with clinical and immunological features indistinguishable from canonical HIGMX-1, no mutation was detected in the coding sequence, in the 5' flanking region, or in the 3' UTR.     

Immunogenicity of the Shigella flexneri Serotype Y (SFL124) Vaccine Strain Expressing Cloned Glucosyl Transferase Gene of Converting Bacteriophage SfX

The glucosyl transferase gene (gtr) from bacteriophage phage X (SfX) caused partial conversion of serotype Y (group antigen 3, 4) to X (group antigen 7, 8) when introduced into a candidate vaccine strain of Shigella flexneri serotype Y (SFL124). The gtr gene caused conversion of O-antigens but did not eliminate the adsorption of the corresponding phage SfX. The hybrid strain expressing both group antigens 7, 8 and 3, 4 showed 75% protection when immunized guinea pigs were challenged with a wild-type S. flexneri serotype X strain. No protection was observed against serotype Y challenge, although group antigen 3, 4 was detected in the LPS of the hybrid strain. This suggests the importance of O-antigen immunity in the host defense against shigellosis.     

Equilibration of [3H]glucosamine and [35S]sulfate with intracellular pools of UDP-N-acetylhexosamine and 3′-phosphoadenosine-5′-phosphosulfate (PAPS) in cultured fibroblasts

Nucleotides and sugar nucleotides were extracted from cultures of human fibroblasts with perchloric acid, separated by isotachophoresis, and quantified by uv absorption analysis at 254 nm. ATP (936 pmol/μg DNA) was, as expected, the dominating nucleotide pool. The energy charge was estimated to 0.9. The UDP-N-acetylhexosamine pool was also a very prominent compound (596 pmol/μg DNA). After incubation of fibroblasts with [³H]glucosamine, more than 95% of the acid-soluble radioactivity was found in the UDP-N-acetylhexosamine pool. Incubation with [³⁵S]sulfate resulted in the incorporation of [³⁵S]sulfate into 3′-phosphoadenosine-5′-phosphosulfate (PAPS). The latter could, however, only be measured as radioactivity, as the amount was too small to be quantified as total mass. Pulse-labeling of fibroblasts with [³⁵S]sulfate and [³H]glucosamine from 5 min to 16 h showed that [³⁵S]PAPS was equilibrated in less than 10 min, while [³H]glucosamine required a longer time, 2–4 h, to attain a steady state with UDP-N-acetylhexosamine. [¹⁴C]Glucose required approximately the same time as [³H]glucosamine to reach steady state with UDP-acetylhexosamine, which suggests that the reason for the long equilibration time is the slow turnover of this pool.     

Transformation of leukotriene A4 methyl ester to leukotriene C4 monomethyl ester by cytosolic rat glutathione transferases

Six major basic cytosolic glutathione transferases from rat liver catalyzed the conversion of leukotriene A4 methyl ester to the corresponding leukotriene C4 monomethyl ester. Glutathione transferase 4-4, the most active among these enzymes, had a Vmax of 615 nmol X min-1 X mg protein-1 at 30 degrees C in the presence of 5 mM glutathione. It was followed in efficiency by transferase 3-4 which had a Vmax of 160 nmol X min-1 X mg-1 under the same conditions. Transferases 1-1, 1-2, 2-2 and 3-3 had at least 30 times lower Vmax values than transferase 4-4.     

The passage of orally fed proteins from mother to foetus in the rat

Pregnant rats were orally fed with a mixture of bovine IgG, bovine albumin, ovalbumin and beta-lactoglobulin. Using immunoprecipitation methods, these proteins were detected in the maternal blood serum, urine and uterine fluids, and also in the foetal blood serum and the amniotic fluid. The results imply that a variety of dietary proteins, still immunoprecipitable, are able to cross the materno-foetal barriers to be detected in the foetal circulation, where they may influence the maturation of the immune system of the foetus.     

Soil microfungi in three Swedish coniferous forests

Microfungi were isolated with the soil washing technique from five different soil horizons in three podzolic coniferous forests in Sweden. Totally 126 species were identified of which 45 were found at two and 24 were found at three sites. The most common genera were Mortierella and Penicillium . Other genera isolated in high frequences were Oidiodendron, Tolypocladium, Trichoderma and Verticillium . Pronounced differences in species composition were found between the soil layers, while great similarities were shown in identical soil layers at different sites.     

Serum Glutathione Peroxidase Activity and Blood Selenium in Pigs

Blood serum glutathione peroxidase activity and blood selenium concentration were measured in blood samples from pigs subjected to experimentally induced selenium deficiency and dietary selenium supplementation on graded levels. A highly significant correlation between blood selenium and serum GSH-Px activity in pigs, especially in selenium deficient pigs, was demonstrated. There was also a strong relationship between blood selenium concentration and serum GSH-Px activity in pigs receiving dietary selenium at graded levels. Serum GSH-Px activity exhibited an excellent close-response relationship to dietary selenium. Linear regression analysis showed that the increased serum GSH-Px activity was a function of the dietary selenium concentration. The fitness of serum in monitoring slight changes of the selenium status of pigs with help of the estimation of GSH-Px activity was discussed. The measurement of serum GSH-Px activity seems to provide a useful and rapid means for defining selenium requirements and for identifying selenium deficiency in growing pigs.     

Combined Therapeutic Effect of Dietary Selenium and Vitamin Ε on Manifested Vesd Syndrome in Weaned Pigs

By using a therapeutic dietary supplementation in pigs, which had developed the vitamin Ε and selenium deficiency (VESD) syndrome, the same amounts of α-tocopheryl acetate and selenium were found to be effective as under prophylactic conditions. The experiment thus supported the conclusions that the addition of 5 mg DL-α-tocopheryl acetate/kg and 135 μg selenium/kg to a diet, which contained only traces of vitamin Ε and selenium, represents a level of minimal requirement. Glutathione peroxidase activity in blood serum was used to evaluate the selenium status in pigs. A modified method for determination of tocopherol in fat tissue was described. The addition of 15 mg α-tocopheryl acetate/kg diet was demonstrated to be sufficient to maintain the tocopherol stores in body fat at an unchanged level.     

Structural studies of the Shigella flexneri variant X, type 5 a and type 5 b O-antigens.

Previous studies of different Shigella flexneri O-antigens indicate that their O-specific region is composed of oligosaccharide repeating units containing a basic tetrasaccharide structure, to which alpha-D-glucopyranosyl groups and O-acetyl groups may be attached to different positions. Structural studies of O-antigens from variant X, type 5a and type 5b lend further support to this assumption. These antigens contain terminal alpha-D-glucopyranosyl groups, one each per repeating unit in X and 5a, two in 5b. The location of these groups in the repeating unit has been determined.