Specific Phosphorylations Transmit Signals from Leukocyte β2 to β1 Integrins and Regulate Adhesion

The regulation of integrins expressed on leukocytes must be controlled precisely, and members of different integrin subfamilies have to act in concert to ensure the proper traffic of immune cells to sites of inflammation. The activation of β₂ family integrins through the T cell receptor or by chemokines leads to the inactivation of very late antigen 4. The mechanism(s) of this cross-talk has not been known. We have now elucidated in detail how the signals are transmitted from leukocyte function-associated antigen 1 and show that, after its activation, the signaling involves specific phosphorylations of β₂ integrin followed by interactions with cytoplasmic signaling proteins. This results in loss of β₁ phosphorylation and a decrease in very late antigen 4 binding to its ligand vascular cell adhesion molecule 1. Our results show how a member of one integrin family regulates the activity of another integrin. This is important for the understanding of integrin-mediated processes.     

The behavior of 9-aminoacridine as an indicator of transmembrane pH difference in liposomes of natural bacterial phospholipids

The behavior of 9-aminoacridine as an indicator of pH differences artificially set across a membrane has been reexamined in liposomes prepared from bacterial phospholipids extracted from chromatophores ofRhodopseudomonas capsulata grown photoheterotrophically. The dye behaves as an ideal indicator for pH differences lower than about three units; at higher pH's the expected linear dependence of Q/(100-Q) vs. pH is no longer strictly observed. Similarly a linear dependence upon the volume of the liposomes added has been verified. The amine ceases to respond to pH changes when the pH of the external medium exceeds the value of 10, corresponding to the pK_a of 9-aminoacridine. The apparent volume of the inner phase of liposomes, as calculated from fluorescence quenching, but not the slope of dependence of fluorescence on pH, appears to be affected by several factors, including the ionic composition, the osmolarity of the external medium, and the microscopic structure of the liposomes. Millimolar concentrations of earth-alkaline cations diminish the apparent internal volume of liposomes, in agreement with the complexing effect of these ions on phospholipid bilayers. The osmotic response of the apparent inner volume has also been verified; this parameter decreases linearly with the reciprocal of the external osmolarity, as expected from the van't Hoff relation; an osmolarity exceeding 0.3 M is, however, necessary in order to observe this effect.     

Paleoepidemiology of cribra orbitalia: Insights from early seventh millennium BP Con Co Ngua,Vietnam

Objectives

We test the hypothesis that the condition(s) leading to the development of cribra orbitalia at Con Co Ngua, an early seventh millennium sedentary foraging community in Vietnam, effectively reduced the resilience of the population to subsequent health/disease impacts. An assessment of both the implications and potential etiology of cribra orbitalia in this specific population is carried out.

Methods

The effective sample included 141 adults aged ≥15 years (53 females, 71 males, and 17 unknown sex) and 15 pre-adults aged ≤14 years. Cribra orbitalia was identified by way of cortical bone porosity of the orbital roof initiated within the diplöic space, rather than initiated subperiosteally. The approach is also robust to the misidentification of various pseudo-lesions. Resultant data was analyzed using Kaplan–Meier survival analysis.

Results

Median survival is higher in adults aged ≥15 years without cribra orbitalia than those with this lesion. For the pre-adult cohort, the opposite pattern is seen where median survival is higher in those with cribra orbitalia than those without.

Conclusion

Adults displayed increased frailty and pre-adults increased resilience with respect to cribra orbitalia. The differential diagnosis for a survival analysis of adults and pre-adults with and without cribra orbitalia included iron deficiency anemia and B12/folate deficiency, parasitism (including hydatid disease and malaria) in addition to thalassemia. The most parsimonious explanation for observed results is for both thalassemia and malaria being the chief etiological agents, while appreciating these conditions interact with, and can cause, other forms such as hematinic deficiency anemias.

     

Interference of inflammation caused by polyester with the development of Yoshida ascite hepatoma in rats. V. Study of cytotoxicity in vitro

It has been known for some years that rats developing a granulomatous inflammation following the intraperitoneal injection of fragments of a polyester suture thread (Mersilene, M) reject a graft of 10(8) Yoshida's ascites hepatoma cells, which on the contrary rapidly grow in M-uninjected animals, originating an ascites tumor and killing the rats in a few days. In this paper granulomatous (TM) and normal (control, C) small pieces of peritoneum (omentum, mesentery and parietal) have been cultivated for 15 h in Eagle-Dul becco's medium together with 10(5) 51Cr-labelled hepatoma cells: the release of the label, an index of cell lysis, was considerably higher in the TM cultures, suggesting a cytotoxic activity of some components of the granulomas. Differences have been observed in the amount of radioisotope released among the TM cultures, suggesting that the particular composition of the cell population may be relevant to the cytotoxicity versus the hepatoma cells.     

Asymmetry of an energy transducing membrane. The location of cytochrome c2 in Rhodopseudomonas spheroides and Rhodopseudomonas capsulata

Monospecific antibodies have been prepared against cytochrome c₂ from Rhodopseudomonas spheroides and Rhodopseudomonas capsulata, and against cytochrome c′ from Rps. capsulata. These antibodies precipitated their respective antigens, but did not cross react with a wide range of procaryotic or eucaryotic cytochromes, or with other bacterial proteins. The cytochromes produced during aerobic growth were immunologically indistinguishable from those produced during photosynthetic growth.Cytochrome c₂ is located in vivo in the periplasmic space between the cell wall and the cell membrane, and when chromatophores are prepared from whole cells the cytochrome becomes trapped inside these vesicles. The implications of these results to energy coupling in the photosynthetic bacteria are discussed.     

Chemotactic activity of the peritoneal lavage fluid of guinea pigs with inflammatory processes caused by the inoculation of various types of suture thread

Minced non adsorbable or adsorbable suture threads introduced into peritoneal cavity of guinea pigs elicit at inflammation with mononuclear and giant cells surrounding suture thread fragments. We studied the presence in the peritoneal cavity of chemotactic factors for PMN cells and we compared the results in relation to the different type of the suture threads used (Dexon, Mersilene, Gore-Tex). The peritoneal cavity was washed, the fluids collected and used as chemotactic agents. The chemotactic response was assayed by employing multiwell chemotaxis chambers (Neuro Probe) and PMNs from normal, non-treated guinea pigs. Quantification of the migration was calculate by chemotactic index (A/B) (B = random migration, A = chemotaxis). The results demonstrate that a chemotactic activity is present in peritoneal fluids following the inflammatory process. This activity is evident at 7th day after Dexon and Mersilene inoculation; using PTFE however, it decreases at 14th d, when the inflammatory process is already developing into healing tissue. In conclusion the chronic inflammation determines the appearance of chemotactic factors for PMN cells; it is suggested that reactive, mononuclear cells, involved in the process, could be responsible for their production and release.