Identification of haptoglobin and apolipoprotein A-I as biomarkers for high altitude pulmonary edema

We have investigated the plasma proteome using 2D gel electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight from patients with high altitude pulmonary edema (HAPE). A complete proteomic analysis was performed on 20 patients with HAPE and ten healthy sea level controls. In total, we have identified 25 protein spots in human plasma and found that 14 of them showed altered changes in HAPE patients, which mainly were acute phase proteins (APPs), compliment components, and apolipoproteins among others. Among the APPs, haptoglobin α2 chain, haptoglobin β chain, transthyretin, and plasma retinol binding precursor showed overexpression in HAPE patients as compared to controls. To validate the result of proteomic analysis, two proteins were selected for enzyme-linked immunosorbent assay and Western blotting analysis. Our data conclusively shows that two proteins, haptoglobin and apolipoprotein A-I are upregulated in plasma of HAPE patients. These proteins may provide a fast and effective control of inflammatory damage until the subsequent mechanisms can begin to operate. Taken together, our findings further support the hypothesis that inflammatory response system is linked to the pathophysiology of HAPE.     

The ionization state of the atmosphere as a function of the meteorological elements and of various sources of ions

The content of positive (N⁺) and negative (N^–) medium ions in the atmosphere, was measured during five periods. The influence of wind velocity and direction, humidity, rainfall and various sources of natural ionization on the N⁺ and N^– content and the relation N⁺/N^– were investigated. Emphasis was placed on the influence of a special kind of weather called chamsin in Israel. The amount of N⁺ and N^– and the relation N⁺/N^– began to increase about 10 hours before the meteorological instruments indicated the specific features of this kind of weather — increase in temperature and decrease in humidity. As some laboratory tests have shown that N^– has a beneficial physiological and biological influence, and N⁺ has the opposite effect, it is assumed that the above-mentioned changes in N⁺/N^– are the cause for persons who are sensitive to this kind of weather, feeling ill. The increase in N⁺ and N^– with the increase in radioactive emanation from the earth and the nuclear tests was established.

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Zusammenfassung Der Gehalt der AtmosphÄre an positiven (N⁺) und negativen (N^–)mittleren Ionen wurde wÄhrend 5 Perioden gemessen. Es wurde nach dem Einfluss der Windgeschwindigkeit und Richtung, der Feuchtigkeit, des Regens und der verschiedenen Quellen der natürlichen Ionisation in der AtmosphÄre gesucht. Spezielle Interesse wurde der besonderen Wetterart, Chamsin, gewidmet. Die Mengen der N⁺ und N^– und das VerhÄltniss N⁺/N^– stieg ca. 10 Stunden bevor die besonderen charakteristischen Eigenschaften dieser Wetterart-steigende Temperatur und abnehmende Feuchtigkeit-sich anzeigten. Da Laboratoriumsversuche einen positiven physiologischen Einfluss der N^– und einen negativen der N⁺ gezeigt haben, mag es sein, dass die oben genannte Zunahme des N⁺/N^– der Grund der Beschwerden von Personen ist die besonders empfindlich auf diese Wetterart reagieren. Eine Zunahme in N⁺ und N^– mit Steigen der Emanation der Erde und der Atombomben Versuche wurde festgestelt.

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Résumé Le contenu de l'atmosphère en ions moyens positifs (N⁺) et négatifs(N^–) a été mésuré pendant 5 periodes. L'influence de la vitesse du vent et de sa direction, de l'humidité, des pluies et de diverses sources d'ionisation naturelle sur le contenu en N⁺ et N^– et sur leur rapport N⁺/N^– a été étudiée. Une attention particulière a été attachée au climat appelé en Israel chamsin. Il a été trouvé que la quantité de N⁺ et de N^– ainsi que leur rapport N⁺/N^– commence à augmenter 10 heures avant que les instruments météorologiques indiquent les caractéristiques essentiels de ce climat(élévation de la température et diminution de l'humidité. Du fait que les essais de laboratoires ont montrés que N^– a un bon effet biologique alors que pour le N⁺ l'effet est opposé, noua pensons que les changements en N⁺/N^– sont a cause de ce que les personnes sensibles à ce genre de climat éprouvent un malaise. Ce genre de personne sent l'approche de ce climat 10 heures à l'avance ou davantage. L'augmentation du contenu en N⁺ et N^– avec l'émanation radioactive de la terre et des essais nucléaires a été établie.

     

A role for DNA polymerase delta in gene conversion and crossing over during meiosis in Saccharomyces cerevisiae

A screen for mutants of budding yeast defective in meiotic gene conversion identified a novel allele of the POL3 gene. POL3 encodes the catalytic subunit of DNA polymerase delta, an essential DNA polymerase involved in genomic DNA replication. The new allele, pol3-ct, specifies a protein missing the last four amino acids. pol3-ct shows little or no defect in DNA replication, but displays a reduction in the length of meiotic gene conversion tracts and a decrease in crossing over. We propose a model in which DNA synthesis determines the length of strand exchange intermediates and influences their resolution toward crossing over.     

Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain

Satellite glial cells (SGCs) tightly envelop the perikarya of primary sensory neurons in peripheral ganglion and are identified by their morphology and the presence of proteins not found in ganglion neurons. These SGC-unique proteins include the inwardly rectifying K(+) channel Kir4.1, the connexin-43 (Cx43) subunit of gap junctions, the purinergic receptor P2Y4 and soluble guanylate cyclase. We also present evidence that the small-conductance Ca(2+)-activated K(+) channel SK3 is present only in SGCs and that SGCs divide following nerve injury. All the above proteins are involved, either directly or indirectly, in potassium ion (K(+)) buffering and, thus, can influence the level of neuronal excitability, which, in turn, has been associated with neuropathic pain conditions. We used in vivo RNA interference to reduce the expression of Cx43 (present only in SGCs) in the rat trigeminal ganglion and show that this results in the development of spontaneous pain behavior. The pain behavior is present only when Cx43 is reduced and returns to normal when Cx43 concentrations are restored. This finding shows that perturbation of a single SGC-specific protein is sufficient to induce pain responses and demonstrates the importance of PNS glial cell activity in the pathophysiology of neuropathic pain.     

Expression and role of serum and glucocorticoid-regulated kinase 2 in the regulation of Na+/H+ exchanger 3 in the mammalian kidney

Serum and glucocorticoid-regulated kinase 2 (sgk2) is 80% identical to the kinase domain of sgk1, an important mediator of mineralocorticoid-regulated sodium (Na(+)) transport in the distal nephron of the kidney. The expression pattern and role in renal function of sgk2 are virtually uncharacterized. In situ hybridization and immunohistochemistry of rodent kidney coupled with real-time RT-PCR of microdissected rat kidney tubules showed robust sgk2 expression in the proximal straight tubule and thick ascending limb of the loop of Henle. Sgk2 expression was minimal in distal tubule cells with aquaporin-2 immunostaining but significant in proximal tubule cells with Na(+)/H(+) exchanger 3 (NHE3) immunostaining. To ascertain whether mineralocorticoids regulate expression of sgk2 in a manner similar to sgk1, we examined sgk2 mRNA expression in the kidneys of adrenalectomized rats treated with physiological doses of aldosterone together with the glucocorticoid receptor antagonist RU486. Northern blot analysis and in situ hybridization showed that, unlike sgk1, sgk2 expression in the kidney was not altered by aldosterone treatment. Based on the observation that sgk2 is expressed in proximal tubule cells that also express NHE3, we asked whether sgk2 regulates NHE3 activity. We heterologously expressed sgk2 in opossum kidney (OKP) cells and measured Na(+)/H(+) exchange activity by Na(+)-dependent cell pH recovery. Constitutively active sgk2, but not sgk1, stimulated Na(+)/H(+) exchange activity by >30%. Moreover, the sgk2-mediated increase in Na(+)/H(+) exchange activity correlated with an increase in cell surface expression of NHE3. Together, these results suggest that the pattern of expression, regulation, and role of sgk2 within the mammalian kidney are distinct from sgk1 and that sgk2 may play a previously unrecognized role in the control of transtubular Na(+) transport through NHE3 in the proximal tubule.     

Technical note: comparison of the Maresh reference data with the who international standard for normal growth in healthy children

The Maresh reference data on stature and long bone lengths in a sample of healthy middle-class children from Denver, Colorado [Maresh: Am J Dis Child 66 (1943) 227-257; Maresh: Am J Dis Child 89 (1955) 725-742; Maresh: Human growth and development (1970) p 155-200], have been used extensively by biological anthropologists to estimate juvenile age and body size using skeletal elements and to assess growth in skeletal series from different ethnic populations or archaeological cultural groups. How well these data reflect the potentially diverse growth patterns of healthy human populations from different geographic areas is unknown. Similarly, the efficacy of using the Maresh reference data to estimate stunting prevalence in prehistoric populations is unknown. This report presents the results from a comparison of the Maresh data on supine length and standing height to the World Health Organization (WHO) international child growth standard. The WHO growth standard is meant to depict typical human growth under optimal conditions and can be used to assess children worldwide, regardless of ethnicity and socioeconomic status. The results from this comparison indicate that although the Maresh reference data generally conform to the WHO standard, reflecting a normal human growth pattern, and therefore serve as a suitable reference for comparative studies of growth patterns, these reference data are not suitable for estimating stunting prevalence.