Showing papers by "University of Turin published in 1994"

The history and geography of human genes

Abstract: The collaboration between the Forensic Community and the scholars of human population genetics, among whom I place myself, has always been fruitful and of reciprocal benefit in Italy as much as in Europe and in North-America, in the latter with a more dialectical attitude as shown by recent rather hot debates. DNA analysis is today offering new possibilities of collaboration. Case work and search for reference populations complement in the daily activity of the forensic scholars. Substantial DNA databases have already been established for a number of population groups, but the development of new standards and new reference databases is likely in the immediate future following the implementation of PCR-based DNA typing systems, and a strong argument can be made for population geneticists to share protocols and markers with the forensic community in order to type well-defined reference populations and from them to contribute to the analysis of human genetic diversity. My talk, however, does not address to the future, but rather to the past: I have had the chance to analyze, over the past ten years, many genetic data from human populations and I am going to give a short review of our recent analyses. Our main interest lies in their interpretation in terms of prehistory and history of our species: a more comprehensive treatment will appear in a forthcoming book written in collaboration with Cavalli-Sforza and Menozzi [1].

Irreversibility and Aggregate Investment

Abstract: Investment is often irreversible: once installed, capital has little or no value unless used in production. This paper proposes and solves a model of sequential irreversible investment and characterizes the aggregate implications of microeconomic irreversibility and idiosyncratic uncertainty. If a large amount of idiosyncratic uncertainty is allowed for, the distributional dynamics induced by the nonlinear character of irreversible investment policies are capable of smoothing the dynamics of aggregate investment (relative to those of its forcing processes) to the extent required by U.S. data.

The origin of the major cystic fibrosis mutation (ΔF508) in European populations

Abstract: delta F508 is the most frequent cystic fibrosis (CF) mutation and accounts for approximately 70% of CF chromosomes worldwide. Three highly polymorphic microsatellite markers have been used to study the origin and evolution of delta F508 chromosomes in Europe. Haplotype data demonstrate that delta F508 occurred more than 52,000 years ago, in a population genetically distinct from any present European group, and spread throughout Europe in chronologically distinct expansions, which are responsible for the different frequencies of delta F508 in Europe.

RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP.

Abstract: RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase. Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes. The major RON transcript is translated into a glycosylated single chain precursor, cleaved into a 185 kDa heterodimer (p185RON) of 35 (alpha) and 150 kDa (beta) disulfide-linked chains, before exposure at the cell surface. The Ron beta-chain displays intrinsic tyrosine kinase activity in vitro, after immunoprecipitation by specific antibodies. In vivo, tyrosine phosphorylation of p185RON is induced by stimulation with macrophage stimulating protein (MSP), a protease-like factor containing four 'kringle' domains, homologous to HGF. In epithelial cells, MSP-induced tyrosine phosphorylation of p185RON is followed by DNA synthesis. p185RON is not activated by HGF, nor is the HGF receptor activated by MSP in biochemical and biological assays. p185RON is also activated by a pure recombinant protein containing only the N-terminal two kringles of MSP. These data show that p185RON is a tyrosine kinase activated by MSP and that it is member of a family of growth factor receptors with distinct specificities for structurally related ligands.

Cu(I)-ZSM-5 zeolites prepared by reaction of H-ZSM-5 with gaseous CuCl: Spectroscopic characterization and reactivity towards carbon monoxide and nitric oxide☆

Abstract: The strongly acidic Bronsted sites of H-ZSM-5 can be quantitatively exchanged with monovalent copper ions by reaction with CuCl at 573 K, as evidenced by the disappearance of the characteristic IR bands of bridged OH groups. Characterization of the Cu-ZSM-5 samples prepared following this route by means of UV-Vis-NIR (diffuse reflectance) and photoluminescence spectroscopies confirms that the protons are substituted by Cu+ ions, which are isolated and located in a few, structurally well defined sites easily accessible to ligand molecules. These Cu+ ions are highly coordinatively unsaturated and can form Cu+ (CO)n (n=1, 2 or 3) carbonylic and Cu+ (NO)n (n=1 or 2) nitrosylic complexes upon dosage of carbon monoxide or nitric oxide at 77 K. The Cu+ (NO)2 dinytrosylic complexes are unstable at room temperature and evolve with formation of nitrous oxide, NO2− and oxidized CuIINO species. This behaviour strongly supports the hypothesis that a redox mechanism is operating in the nitric oxide decomposition reaction leading to nitrogen and oxygen.

Overexpression of the MET/HGF receptor in ovarian cancer

Abstract: The MET oncogene encodes the receptor for Hepatocyte Growth Factor/Scatter Factor, a unique growth factor that induces not only proliferation of epithelial cells, but also cell motility and invasiveness. DNA level and expression of the Met/HGF receptor gene were examined with Southern- and Western-blot analyses, respectively, in human ovary, benign ovarian tumors and epithelial ovarian carcinomas. The Met/HGF receptor was detectable in the surface epithelium of normal ovary. The level of expression was unchanged in benign ovarian tumors of various origins. Fourteen out of 67 malignant carcinomas (20%) showed a 3-to 10-fold increase in expression. In 5 additional cases the Met/HGF protein was overexpressed over 50-fold. This represents a total of 28% of cases. Overexpression was not associated with MET gene amplification. Overexpressing tumors belonged to different histotypic variants, but showed a well-differentiated phenotype. Clinically, overexpression was associated with disease at any pathologic stage, but was significantly correlated with premenopausal status of patients. These data suggest that expression of the Met/HGF receptor may add a selective growth advantage to a narrow subset of differentiated ovarian cancers in premenopausal patients.

Tyrosines1234-1235 are critical for activation of the tyrosine kinase encoded by the MET proto-oncogene (HGF receptor).

Abstract: The tyrosine kinase encoded by the MET proto-oncogene (p190MET) is the receptor for Hepatocyte Growth Factor/Scatter Factor (HGF/SF). Previous work has shown that autophosphorylation of p190MET enhances its enzymatic activity and that the major phosphorylation site is Tyr1235, located in the catalytic domain. This residue is part of a 'three tyrosine' motif, including Tyr1230, Tyr1234, and Tyr1235, conserved in several other receptor kinases. We studied the role of these tyrosines in the positive regulation of the p190MET kinase by site-directed mutagenesis. Substitution of either Tyr1235 or Tyr1234 with phenylalanine severely reduced the in vitro kinase activity toward exogenous substrates. Kinetic experiments showed that the residual activity of these mutants could still be enhanced by autophosphorylation. Phosphopeptide mapping indicated that, in the absence of Tyr1235, Tyr1234 is phosphorylated. Only the replacement of both Tyr1234 and Tyr1235 yielded a mutant which completely lost the ability to be activated by autophosphorylation. In stable transfectants expressing the HGF/SF receptor with single substitution of either Tyr1234 or Tyr1235 the response to HGF/SF was impaired. The ligand did not induce tyrosine phosphorylation of the receptor nor stimulated chemotaxis. These data show that Tyr1234 and Tyr1235 are critical for the activation of the HGF/SF receptor kinase both in vitro and in response to the ligand in intact cells.

A Study of Apoptosis in Normal and Pathologic Nervous Tissue After In situ End-Labeling of DNA Strand Breaks

Abstract: Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks through incorporation of labeled nucleotides. We have applied two ISEL assays to physiological and pathological conditions affecting the nervous system in which PCD is likely to occur. Terminal transferase assay was more sensitive than DNA polymerase assay and allowed the recognition of a larger number of cells than conventional histology. Apoptotic cells were readily found in the developing spinal cord and dorsal root ganglia. Medulloblastomas, gliomas, brain lymphomas and metastases showed abundant apoptotic cells either isolated or grouped in small foci. Labeling was also found in cells without a clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's disease, amyotrophic lateral sclerosis and human and mouse prionic encephalopathies. Our results show that ISEL is a useful technique for demonstrating apoptotic cells in nervous tissue during development and in brain tumors. Lack of staining in neurodegenerative diseases suggests that other types of PCD might be involved.

Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas)

Abstract: Since 1989, 45 patients [pts; 26 females and 19 males, aged 19-79 yr (median, 58)] bearing incidentally discovered adrenal masses were studied. The aim of the study was to verify the prevalence of hormone activity in clinically silent adrenal masses. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of PRA and aldosterone levels in clino- and orthostatic posture, and basal and dynamic [dexamethasone (dex) suppression and ovine CRH stimulation] evaluation of hypothalamic-pituitary-adrenal axis. The most frequent finding was the reduction of dehydroepiandrosterone sulfate (DHEA-S) levels below the third percentile of controls in 19 (42%) pts. DHEA-S levels were significantly lower in pts than in controls [68 (range, 5-1000) vs. 208 (34-326) micrograms/dL; 1.8 (0.1-27.1) vs. 5.6 (0.9-8.8) mumol/L; P < 0.001]. Three pts (7%) had high 24-h mean serum cortisol levels, and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dex suppressibility was found in 15% of pts vs. 8% of controls (P < 0.05). ACTH and cortisol responses to ovine CRH did not significantly differ between pts and controls, although blunted ACTH responses were found in 22% of the cases. The above-mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression, but able to inhibit to some extent the hypothalamic-pituitary-adrenal axis. These results indicate that silent cortisol hypersecretion is frequently observed in pts with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely. Indeed, the size of the mass and the hormone pattern remained substantially unchanged in 9 pts followed up for 12 months. From merely a cost/benefit ratio, the evaluation of DHEA-S levels and dex suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

Creation of an hepatocyte growth factor/scatter factor autocrine loop in carcinoma cells induces invasive properties associated with increased tumorigenicity.

Abstract: Exogenous HGF/SF converts subconfluent cultures of NBT-II epithelial carcinoma cells into mobile fibroblast-like cells while being only mitogenic for cells maintained at high density To investigate the potential role of such factor in tumor progression, we generated HGF/SF-producing NBT-II cells by transfection with an expression plasmid containing human HGF/SF cDNA HGF/SF-producing cells also exhibit a fibroblastic phenotype Media conditioned by these cells are potent inducers of in vitro tubulogenesis which can be inhibited with specific anti-HGF/SF antibodies; these antibodies are also able to reverse the scattered phenotype of the HGF/SF-producing cells In addition spheroids of HGF/SF-producing cells are dispersed into 3D collagen gels suggesting an increase of invasive properties of these cells When injected in nude mice, these HGF/SF-producing cells induce tumors appearing more rapidly than did those obtained with untransfected cells These results show that HGF/SF can promote motility and invasive properties of NBT-II bladder carcinoma cells and also confers a tumorigenic advantage when acting as an autocrine factor

Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene or admixed with conventional adjuvants.

Abstract: To evaluate the efficacy of vaccinations with cytokine-gene-transduced tumor cells, BALB/c mice were challenged with 1 × 10 5 parental cells of a syngeneic adenocarcinoma cell line (TSA-pc). No protection was observed in mice immunized 30 days earlier with 1 × 10 5 nonreplicating mitomycin-C-treated TSA-pc alone, or with Corynebacterium parvum or Complete Freund Adjuvant (CFA). Ten to 30% of mice immunized with nonreplicating cells engineered to produce interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and γ-interferon gene were protected. Fifty % of mice immunized with replicating TSA-pc admixed with C. parvum and 80–100% of mice immunized with replicating tumor cells transduced with IL-2, IL-4, IL-7, IL-10, or γ-interferon gene were protected. No cure was afforded by TSA cells admixed with C. parvum or CFA, nor by TSA cells engineered with IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α gene injected starting 1 day after TSA-pc challenge. Complete tumor regression, however, was obtained in 10–20% of mice treated with TSA cells transduced with IL-2, IL-4, IL-7, or IL-10 and in 30% of those treated with TSA cells transduced with γ-interferon gene.

Carotid plaque, aging, and risk factors. A study of 457 subjects.

Abstract: The aim of this study was to assess the prevalence of extracranial carotid artery atherosclerosis and its relation to principal cardiovascular risk factors at different ages in a sample of the general population.B-mode ultrasonography was used to investigate the carotid district in 457 subjects (231 men and 226 women; mean age, 55.4 +/- 18.7 years; range, 18 to 97 years) in the metropolitan area. The ultrasonographic findings were then related to risk factors.Carotid plaques were found in 178 subjects (38.9%). The prevalence of atherosclerosis, number of plaques, and severity of stenosis were observed to increase with age. Age (P < .0001), cigarette smoking (P < .0001), male sex (P < .001), total cholesterol (P < .05), and, inversely, the ratio of high-density lipoprotein cholesterol to total cholesterol (P < .05) were found to be independently associated with carotid atherosclerosis. Stratified analysis by sex and age showed effect modifications by age on cigarette smoking, total cholesterol, and the rat...

The Universality of vacuum Einstein equations with cosmological constant

Abstract: It is shown that for a wide class of analytic Lagrangians, which depend only on the scalar curvature of a metric and a connection, the application of the so called `Palatini formalism', i.e. treating the metric and the connection as independent variables, leads to `universal' equations. If the dimension n of spacetime is greater than two these universal equations are vacuum Einstein equations with cosmological constant for a generic Lagrangian and are suitably replaced by other universal equations at degenerate points. We show that degeneracy takes place in particular for conformally invariant Lagrangians and we prove that their solutions are conformally equivalent to solutions of Einstein's equations. For two-dimensional spacetimes we find instead that the universal equation is always the equation of constant scalar curvature; in this case the connection is a Weyl connection, containing the Levi-Civita connection of the metric and an additional vector field ensuing from conformal invariance. As an example, we investigate in detail some polynomial Lagrangians and discuss their degenerate points.

Dynamics of .alpha.-CH Deprotonation and .alpha.-Desilylation Reactions of Tertiary Amine Cation Radicals

Abstract: Time-resolved laser spectroscopy has been used to generate and characterize a series of tertiary amine cation radicals and to determine the rates of their a-CH deprotonation and a-desilylation reactions with bases and silophiles. Laser excitation (308 nm) of a 60:40 Me0H:MeCN solution of PhNMe2 (DMA) and 1,4-dicyanobenzene (DCB) promotes SET-induced formation of the DMA cation radical (460 nm) and DCB anion radical (340 nm), which undergo decay by back electron transfer at nearly equal rates and with respective second-order rate constants of 1.1 X 1Olo and 1.3 X 1010 M-1 s-l (25 "C). The decay rate is lowered (ca. 4-fold) by the inclusion of salts (ca. 0.1 M) such as nBu4NC104, LiC104, nBu4NC1, nBu4NBF4, and nBu4N03SCF3 in MeOH-MeCN and by changing the solvent from MeCN to MeOH and to EtOH. The cation radical of PhNMeCHz(TMS) (480 nm) and the simultaneously generated DCB anion radical undergo second order decay in MeCN with respective rate constants of 1.2 X 10'0 and 9.9 X lo9 M-1 s-1 (25 "C). The silylamine cation radical decay rate was found to be governed by the concentration of silophiles (MeOH, H20, and nBu4NF) in MeCN solutions. The observations are consistent with a silophile-induced desilylation The rate of DMA cation radical decay is a function of base concentration. Both nBu4NOAc and nBu4N02CCF3 react with the DMA cation radical (in 60:40 Me0H:MeCN containing 0.1 M nBu4NC104) with second-order rate constants for a-CH deprotonation of 3.1 X 105 and 8 X lo4 M-l s-l (25 "C), respectively. Measurements with PhN(CD& and nBu4NOAc gave a kH/kD for a-CH deprotonation of 3.6 (60:40 MeOH:MeCN, 25 "C). Para-substituents have a pronounced effect on the rate of a-CH deprotonation by nBu4NOAc; second-order rate constants of 2.3 X lo4, 1.1 X lo5, and 2.5 X lo6 M-1 s-l were determined for thep-OMeC6H4NMez, p-MeC&NMez and p-CF3C6H4NMe2 cation radicals. Studies with Ph2NMe demonstrated that its cation radical (645 nm) can be generated by SET to DCB and that its decay through a-CH deprotonation by nBu4NOAc has a second-order rate constant of 9.5 X lo$ M-1 s-1 and a kH/kD value of 2.8 (25:75 MeOH:MeCN, 25 "C). Finally, the effects of a-substituents on the rates of nBu4NOAc-induced a-CH deprotonation of tertiary amine cation radicals were evaluated by use of the amines Ph2NCHRlR2. The second-order rate constants (25 "C, 25:75 Me0H:MeCN) are 2.3 X lo$ (RI = Me, RZ = H), 1.7 X 105 (RI = process with second-order rate constants of 8.9 X lo5 (MeOH), 1.27 X lo6 (HzO), and 3.1 X lo9 M-* s-l ( n Bu~NF) . R2 = Me), 3.2 X 106 (R1 = Ph, R2 = H), 2.6 X lo6 (R1 = CH=CH2, R2 = H), and 7.0 X lo7 M-1 s-l (RI = m C H , Rz = H).

In vitro marginal adaptation of alumina porcelain ceramic crowns

Abstract: This study evaluated the dimensional stability during firing of In-Ceram alumina porcelain ceramic and examined the marginal fit for three different configurations of tooth preparation. A stereomicroscope was used to measure the space between the margin of restorations and tooth preparations. The three methods of tooth preparation were statistically compared and revealed suitable dimensional stability during the firing and glazing process. A better marginal fit was recorded for artificial crowns fabricated on a chamfer or 50-degree shoulder tooth preparation.

Measurement of total and partial photon proton cross sections at 180 GeV center of mass energy

Abstract: Photon proton cross sections for elastic light vector meson production, σelνp, inelastic diffractive production, σndνp, non-diffractive production, σdνp, as well as the total cross section, σtotνp, have been measured at an average υp center of mass energy of 180 GeV with the ZEUS detector at HERA. The resulting values are σelνp = 18 ± 7 μb, σdνp = 33 ± 8 μb, σndνp = 91 ± 11 μb, and σtotνp 143 ± 17 μb, where the errors include statistical and systematic errors added in quadrature.

Laparoscopic management of symptomatic nonparasitic cysts of the liver : indications and results

Abstract: OBJECTIVE: This clinical study evaluated the results of and defined the indications for laparoscopic fenestration of symptomatic nonparasitic hepatic cysts, either solitary or diffuse. SUMMARY BACKGROUND DATA: Different surgical treatments have been proposed for highly symptomatic hepatic cysts: enucleation, fenestration, hepatic resection, and liver transplantation. The advent of laparoscopic surgery has given new opportunities but, at the same time, has increased the uncertainties concerning the proper management of these patients. METHODS: Eight patients with solitary cysts and nine with polycystic liver and kidney disease (PLD) were seen during a period of 2 years. After a careful review of the symptoms, 6 patients were excluded from surgical treatment and 11 (4 solitary cysts and 7 PLD) were treated by laparoscopic fenestration. Postoperative morbidity and mortality rates, hospital stay, and clinical early and late results were evaluated. RESULTS: In the solitary cyst group, there was no surgical morbidity or deaths, and a complete regression of symptoms occurred in all patients. No recurrences were observed. In the PLD group, two patients had to be converted to laparotomic fenestration (28%). There were no deaths, and the surgical morbidity was limited to two cases of postoperative ascites. Symptomatic relief was obtained in 80% of patients, but the symptoms recurred in 60%. A subgroup of PLD at high risk for recurrence was identified. CONCLUSIONS: The best indications for laparoscopic fenestration seem to be solitary cyst and PLD characterized by large cysts mainly located on the liver surface (type 1), whereas PLD characterized by numerous small cysts all over the liver (type 2) should be considered a contraindication to laparoscopic fenestration.

CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells

Abstract: The present study demonstrates that an agonistic anti-CD38 monoclonal antibody (mAb) (IB4) is capable of preventing apoptosis of human tonsillar germinal center (GC) B cells as measured by either morphological methods on Giemsa-stained cytospin preparations or flow cytometry on propidium iodide-stained cells. Two other anti-CD38 mAb (Leu-17 and OKT10) consistently failed to prevent apoptosis in the same cells, even when tested over a wide range of concentrations. Furthermore, exposure of GC B cells to IB4 mAb up-regulates the bcl-2 proto-oncogene product in a manner similar to that observed with CD40 ligand (CD40L). The ability of IB4 mAb to prevent apoptosis of GC B cells was inferior to that of both anti-CD40 mAb and CD40L. No synergistic or additive effects were observed when IB4 mAb was used together with CD40L. Unlike anti-CD40 mAb or CD40L, IB4 mAb neither induced a proliferation of GC B cells nor increased their proliferative response to anti-CD40, CD40L or recombinant interleukin-4, used alone or in combination. The present results are consistent with the recent findings on either the feature of the CD38 molecules to deliver activation signals and on the mechanisms of selection of B cells that operates in the GC.

Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man.

Abstract: We evaluated the GH-releasing activity of hexarelin, a new synthetic hexapeptide, after i.v. (1 and 2 micrograms/kg), sc (1.5 and 3 micrograms/kg), intranasal (20 micrograms/kg), and oral (po; 20 and 40 mg) administration to 12 healthy young volunteers. Reference treatments were i.v. saline and GH-releasing hormone (GHRH; 1 microgram/kg). GH release (mean +/- SEM) after the i.v. dose of 1 microgram/kg hexarelin [area under the curve (AUC), 3175 +/- 506 micrograms/min.L] was about 2 times higher than that induced by 1 microgram/kg GHRH (AUC, 1544 +/- 161 micrograms/min.L; P < 0.001). Hexarelin (2 micrograms/kg, i.v.) elicited a further increase in GH levels (AUC, 4422 +/- 626 micrograms/min.L) compared to the 1 microgram/kg dose. The GH response to 2 micrograms/kg hexarelin, i.v., was very reproducible (AUC, 4016 +/- 563 vs. 3959 +/- 803 micrograms/min.L). The sc administration of hexarelin produced a dose-dependent GH response (AUC, 3180 +/- 392 and 4459 +/- 566 micrograms.min.L with 1.5 and 3 micrograms/...

Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis.

Abstract: Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic properties of this agent might be consequent to the production of secondary mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor (PAF) by monocytes and endothelial cells, we investigated the possible involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was studied in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover, in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h after TNF-alpha injection. The synthesis of PAF within the Matrigel was concomitant with the early migration of endothelial cells and infiltration of monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was observed. Synthetic PAF as well as PAF extracted and purified from mice challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB 2170. These results suggest that the angiogenic effect of TNF-alpha is, at least in part, mediated by PAF synthesized from monocytes and/or endothelial cells infiltrating the Matrigel plug.

Quantum-mechanical calculation of the solid-state equilibrium MgO+α-Al 2 O 3 ⇄MgAl 2 O 4 (spinel) versus pressure

Abstract: The ground-state crystal energies of cubic ${\mathrm{MgAl}}_{2}$${\mathrm{O}}_{4}$ (spinel) and MgO (periclase) and of rhombohedral \ensuremath{\alpha}-${\mathrm{Al}}_{2}$${\mathrm{O}}_{3}$ (corundum) have been calculated at different volumes, relaxing the corresponding structures, by all-electron periodic Hartree-Fock methods (crystal program) Basis sets of contracted Gaussian-type functions are employed for the 18 atomic (including d) orbitals representing each of the Mg, Al, and O atoms Mulliken net atomic charges ${\mathit{z}}_{\mathrm{Mg}}$=186\ensuremath{\Vert}e\ensuremath{\Vert} (MgO), ${\mathit{z}}_{\mathrm{Al}}$=230\ensuremath{\Vert}e\ensuremath{\Vert} (\ensuremath{\alpha}-${\mathrm{Al}}_{2}$${\mathrm{O}}_{3}$), ${\mathit{z}}_{\mathrm{Mg}}$=174\ensuremath{\Vert}e\ensuremath{\Vert}, and ${\mathit{z}}_{\mathrm{Al}}$=224\ensuremath{\Vert}e\ensuremath{\Vert} (spinel) are obtained The elastic bulk modulus, the Murnaghan equation of state p(V) at the athermal limit, the Mg-O and Al-O bond compressibilities, and the binding energy have been derived for each phase (and the elastic constants ${\mathit{C}}_{11}$ and ${\mathit{C}}_{12}$ for spinel only) Comparison with existing experimental data is discussed The enthalpy change for spinel decomposition into the simple oxides has been computed as a function of pressure, including a correction for the electron correlation energy based on local-density-functional theory A decomposition pressure of 11 GPa at T=0 K is predicted, against values of 8 and 13 GPa derived from experimental thermodynamic data and from direct compression experiments, respectively

Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule.

Abstract: CD38 is a type II transmembrane glycoprotein, which is widely used as a marker for immature and activated lymphocytes, as well as plasma cells. Although its functional role and natural ligand are not known, CD38 has been shown to transduce activation signals to lymphocytes. Our work shows that CD38 is preferentially expressed by CD4+CD45RA+ cells, but not by CD4+CD45R0+ cells. CD4+CD45RA+ cells are reported to respond poorly to stimuli acting through the CD3/TCR in vitro and to display unique migration pathways in vivo. Cross-linking of CD38 by mAb did not overcome the hyporesponsiveness of CD4+ resting/naive cells to several activation stimuli; in contrast, CD38 engagement by mAb specifically inhibited their binding with human vein endothelial cells. These data suggest that CD38 may play a role in lymphocyte migration. The same inhibitory effect was detected on the (human x mouse) hybrid cell line CP410.A10, which expresses human CD38, but not on its CD38- subclone CP14. CD38 mAb did not inhibit the conventional binding assay between endothelium and several human CD38+ T and B cell lines. However, the inhibition was apparent when the binding assay was performed at 4 degrees C on a rocking shelf, conditions that minimized integrin function. These data suggest that CD38 mediates weak cell binding to endothelium, which is effective even in dynamic conditions. These features are reminiscent of those exerted by selectins, which are adhesion molecules that account for leukocyte rolling on vascular endothelial cells and play an important role in lymphocyte homing.