Showing papers by "University of Lausanne published in 1988"

Neurotization in brachial plexus injuries. Indication and results.

Abstract: In neurotization or nerve transfer, a healthy but less valuable nerve or its proximal stump is transferred in order to reinnervate a more important sensory or motor territory that has lost its innervation through irreparable damage to its nerve. In brachial plexus injuries, extraplexal nerves such as the spinal accessory nerve, rami of the cervical plexus, or intercostal nerves are transferred onto trunks, cords, or individual nerves or else segments of the brachial plexus that maintain continuity with the spinal cord may be coapted to trunks or cords the surgeon wishes to innervate. This method is particularly indicated in root avulsion injuries that occur frequently following traction trauma to the brachial plexus. The authors convey their experience with neurotization using the long thoracic nerve in seven cases, the accessory nerve in 30 cases, intercostal nerves in 66 cases, and various nerve transfers within the plexus in 31 cases. Results of other authors are also reported. With these methods, it is possible to obtain good elbow flexion in more than one-half of patients; however, only limited shoulder function and no useful finger function are obtained.

Granzymes, a family of serine proteases released from granules of cytolytic T lymphocytes upon T cell receptor stimulation.

Abstract: The cytolytic potential of T effector cells appears to be intimately related to the presence of proteins stored in specialized cytoplasmic granules. A striking biological property of isolated granules is their lytic activity for a variety of target cells in a nonrestricted manner. Proteins contained within these granules of CTLs are specifically released upon target cell recognition. We have isolated and characterized six granule-associated proteins in two murine CTL lines in addition to the pore-forming and target membrane-disrupting perforin. Six full length cDNA clones have been identified in a CTL-specific cDNA expression library which code for the granule-associated serine esterases, designated as granzymes A to F. Granzymes A and B represent the genuine proteins encoded by the H factor/CTLA-3 cDNA and the CTLA-1/CCPI cDNA, respectively. The covalent amino acid structures of all six granzymes show the hallmarks for serine proteases and are highly related to that of rat mast cell protease I and II and cathepsin G, which have been found in granules of mast cells and neutrophilic granulocytes, respectively. The primary translation products are processed by removal of a hydrophobic signal peptide and a two residue-long propeptide at the amino-terminus. Immuno-electron microscopy shows that granzymes and perforin are stored together within secretory granules of CTLs. Simultaneous release of at least two of these granzymes has been observed during degranulation of a murine CTL line by anti-T3 antibodies. The biological role, particularly the proteolytic events elicited by granzyme A and other granzymes in the context of target cell recognition, are not known at present. It is unlikely that they form a proteolytic activation cascade together with pore-forming proteins analogous to the complement system. The strictly regulated secretion of granzymes and the lack of measurable enzymatic activity in the case of granzymes B, C, E and F towards a variety of synthetic substrates suggest a highly specific function for each of them.

Organization of feedback and feedforward projections of the barrel cortex: a PHA-L study in the mouse

Abstract: In order to analyze the organization of the efferent projections of single barrel columns (BC, i.e. a barrel in layer IV of parietal cortex plus the cortical tissue above and below it), we made small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin in the barrel cortex of 20 adult mice. On the basis of reconstructions of the sites of terminal labelling, the brain regions receiving projections from the barrel cortex could be identified and classified in five groups. Each group is characterized by the topography of the distribution of efferents arising from a single BC. The projections to the trigeminal sensory complex are point to point: i.e. one BC projects only to the site of termination of the primary sensory neurons innervating the corresponding whisker follicle. In the ventrobasal thalamic nucleus BC projections are not restricted to the corresponding barreloid; instead they contact parts of barreloids belonging to one arc. In the reticular and posterior thalamic nuclei the projections from a row of BC's converge to a collective termination site, whereas in the superior colliculus the projections from an arc of BC's converge to a common termination site. There is a complete overlap of BC projections in restricted zones within SII, motor cortex, perirhinal cortex, contralateral barrelfield, caudoputamen and pons. The organization of the efferents from the barrel cortex demonstrates a contrast between feedback and feedforward projections from this important area of neocortex.

A major 125-kd membrane glycoprotein of Saccharomyces cerevisiae is attached to the lipid bilayer through an inositol-containing phospholipid

Abstract: A number of plasma membrane glycoproteins of mammalian and protozoan origin are released from cells by phosphatidylinositol-specific phospholipase C. Some of these proteins have been shown to be attached to the lipid bilayer via a covalently linked, structurally complex glycophospholipid. Here we establish the existence of similarly linked glycoproteins in the yeast Saccharomyces cerevisiae. The most abundant of these is a tightly membrane-bound glycoprotein of 125 kd. The detergent-binding moiety of this protein can be removed by phosphatidylinositol-specific phospholipase C of bacterial origin or from Trypanosoma brucei. Metabolic labeling indicates that the protein contains covalently attached fatty acid and inositol. It also contains the cross-reacting determinant (CRD), an antigen found previously on the glycophospholipid anchor of protozoan and mammalian origin. Treatment of the protein with endoglycosidases F and H results in a 95-kd species. In the secretion mutant sec18, grown at 37 degrees C, the vesicular transport of glycoproteins is reversibly blocked between the rough endoplasmic reticulum and the Golgi apparatus. We find that sec18 cells, when grown at 37 degrees C, do add phospholipid anchors to newly synthesized glycoproteins. This indicates that these anchors are added in the rough endoplasmic reticulum.

The heparin binding domain of S-protein/vitronectin binds to complement components C7, C8, and C9 and perforin from cytolytic T-cells and inhibits their lytic activities

Abstract: S-Protein/vitronectin is a serum glycoprotein that inhibits the lytic activity of the membrane attack complex of complement, i.e., of the complex including the proteins C5b, C6, C7, C8, and C9n. We show that intact S-protein/vitronectin or its cyanogen bromide generated fragments also inhibit the hemolysis mediated by perforin from cytotoxic T-cells at 45 and 11 microM, respectively. The glycosaminoglycan binding site of S-protein/vitronectin is responsible for the inhibition, since a synthetic peptide corresponding to a part of this highly basic domain (amino acid residues 348-360) inhibits complement- as well as perforin-mediated cytolysis. In the case of C9, the synthetic peptide binds to the acidic residues occurring in its N-terminal cysteine-rich domain (residues 101-111). Antibodies raised against this particular segment react 25-fold better with the polymerized form of C9 as compared with its monomeric form, indicating that this site becomes exposed only upon the hydrophilic-amphiphilic transition of C9. Since the cysteine-rich domain of C9 has been shown to be highly conserved in C6, C7, and C8 as well as in perforin, the inhibition of the lytic activities of these molecules by S-protein/vitronectin or by peptides corresponding to its heparin binding site may be explained by a similar mechanism.

High-pressure NMR kinetics. Part 34. Variable-temperature and variable-pressure NMR kinetic study of solvent exchange on hexaaquaruthenium(3+) and -(2+) and hexakis(acetonitrile)ruthenium(2+)

Abstract: Water exchange on ruthenium(II) and ruthenium(III) was studied by /sup 17/O NMR and acetonitrile exchanges on ruthenium(II) was studied by /sup 1/H NMR spectroscopy as a function of temperature and pressure. The kinetic parameters reported for Ru(II) imply that the solvent exchange on Ru/sup 2+/ occurs via an interchange I mechanism for both H/sub 2/O and CH/sub 3/CN. The kinetic parameters are also reported for Ru(III). These data are conclusive for an associative interchange I/sub a/ mechanism for water exchange on Ru(H/sub 2/O)/sub 6//sup 3+/ but for an I mechanism on the deprotonated species Ru(H/sub 2/O)/sub 5/(OH)/sup 2+/. These mechanistic results for low-spin ruthenium solvates are compared to those of other di- and trivalent transition-metal ions. 39 references, 8 figures, 5 tables.

The surpluses immediately before and at ruin, and the amount of the claim causing ruin

Abstract: In the classical compound Poisson model of the collective risk theory we consider X, the surplus before the claim that causes ruin, and Y, the deficit at the time of ruin. We denote by f(u; x, y) their joint density (u initial surplus) which is a defective probability density (since X and Y are only defined, if ruin takes place). For an arbitrary claim amount distribution we find that f(0; x, y) = ap(x + y), where p(z) is the probability density function of a claim amount and a is the ratio of the Poisson parameter and the rate of premium income. In the more realistic case, where u is positive, f(u; x, y) can be calculated explicitly, if the claim amount distribution is exponential or, more generally, a combination of exponential distributions. We are also interested in X + Y, the amount of the claim that causes ruin. Its density h(u; z) can be obtained from f(u; x, y). One finds, for example, that h(0; z) = azp(z).

Risk factors for hepatocellular carcinoma in northern Italy.

Abstract: The role of socio-demographic factors, lifestyle habits and selected dietary factors on the risk of hepatocellular carcinoma was evaluated in a hospital-based case-control study conducted in Northern Italy on 151 patients with hepatocellular carcinoma and 1,051 controls in hospital for acute, non-neoplastic or digestive conditions, unrelated to any of the known or potential risk factors for primary liver cancer. There were significant inverse relationships with levels of education and social class (relative risk, RR = 1.9 and 2.4 for lower vs. upper categories), and positive associations with clinical history of hepatitis (RR = 3.5, 95% confidence interval = 2.0-6.0) or liver cirrhosis (RR = 15.6, 95% CI = 8.3-29.4). The relative risk was not elevated in smokers and light or moderate alcohol drinkers, but the point estimate was above unity among heavy drinkers (RR = 1.5, 95% CI = 1.0-2.4). Among 14 food items considered, including important sources of vitamin A, protein and fats in the Italian diet, 5 were inversely and significantly related to liver cancer risk. This suggests that a diet deficient in several aspects may be related to hepatocellular carcinoma.

Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes.

Abstract: Human rTNF/Cachectin was shown to stimulate gene transcription of plasminogen activator inhibitor (PA1)-1 and PAI-2, and simultaneously suppress constitutive gene expression of tissue-type plasminogen activator (t-PA) in human fibrosarcoma cells. We propose that a TNF-mediated reprogramming of gene transcription induces, in appropriate target cells, an anti-fibrinolytic state, which may cooperate with the induction of procoagulant activity (tissue factor) to stabilize the fibrin deposits commonly found in inflamed tissue. PAI genes also provide a model system for a study of the molecular pathways underlying TNF-mediated signal transduction.

Characterization of granzymes A and B isolated from granules of cloned human cytotoxic T lymphocytes.

Abstract: A human CD8+ CTL clone with cytolytic potential was shown to express two serine proteases, a 50-kDa homodimer and a 27-kDa monomer, which were purified from cytoplasmic granules. N-terminal sequencing of the purified proteins revealed that the 50-kDa homodimer is the gene product of the human Hanukah factor cDNA clone and that it represents the human homologue to granzyme A. Similarly, the 27-kDa protein was shown to be the serine esterase encoded by the human lymphocyte protease cDNA clone and corresponds to granzyme B. There was no evidence for the presence of other granzymes, in particular for the human homologues to murine granzymes C, D, E, and F. The substrate best cleaved by granzyme A was Gly-Pro-Arg-amido-4-methyl-coumarin after the Arg residue and the pH optimum was 8 to 8.5. Upon triggering of the TCR-CD3 complex with an anti-CD3 mAb, granzyme A was released into the culture medium. Furthermore, a granule-associated hemolytic activity was detected after salt extraction and partial purification of granule proteins. This suggests that hemolytically active human perforin can be obtained from inactive granules.

Energetic strategies of shrews: ecological constraints and evolutionary implications

Abstract: Data on various features influencing resource acquisition and allocation of energy in Soricidae are reviewed. The relationships between these features are examined at the three functional levels that constrain the energetic design of shrews: the maintenance of homeostasis (rate of metabolism and temperature regulation), the balancing of the energy budget (e.g. the influence of body mass, activity rate, various energy saving mechanisms and home range size), and the allocation of energy towards reproduction (e.g. the influence of litter size). Two major contradictory energetic designs may be recognized: one rather expensive design that is observed in cold and temperate climates with relatively predictable fluctuations in resource availability (e.g. in Sorex and Neomys), and another much less expensive design that is observed mainly in warm or unpredictable environments (e.g. in Crocidura, Suncus and Notiosorex). It is speculated that climate and resource availability impose narrow limits on the evolution of these energetic strategies, mainly because of the small thermal inertia and reduced energetic autonomy of shrews.

Acetylcholinesterases from Musca domestica and Drosophila melanogaster Brain Are Linked to Membranes by a Glycophospholipid Anchor Sensitive to an Endogenous Phospholipase

Abstract: The sensitivity of acetylcholinesterases (AChEs) from Musca domestica and from Drosophila melanogaster to the phosphatidylinositol-specific phospholipase C from Bacillus cereus and to the glycosylphosphatidylinositol-specific phospholipase C from Trypanosoma brucei was investigated. B. cereus phospholipase C solubilizes membrane-bound AChE, and both phospholipases convert amphiphilic AChEs into hydrophilic forms of the enzyme. The Upases uncover an immunological determinant that is found on other glycosylphosphatidylinositol-anchored membrane proteins after the same treatment. This immunological determinant is also present on the native hydrophilic form of AChE. The polypeptide bearing the active site of the membrane-bound enzyme migrates faster during sodium dodecyl sulfate-polyacrylamide gel electrophoresis than the same polypeptide from the soluble enzyme. We conclude that AChE from insect brain is attached to membranes via a glycophospholipid anchor. This anchor is covalently linked to the polypeptide bearing the active esterase site of the enzyme and can be cleaved by an endogenous lipase.

Development of projections from auditory to visual areas in the cat.

Abstract: In newborn kittens, cortical auditory areas (including AI and AII) send transitory projections to ipsi- and contralateral visual areas 17 and 18. These projections originate mainly from neurons in supragranular layers but also from a few in infragranular layers (Innocenti and Clarke: Dev. Brain Res. 14:143-148, '84; Clarke and Innocenti: J. Comp. Neurol. 251:1-22, '86). The postnatal development of these projections was studied with injections of anterograde tracers (wheat germ agglutinin-horseradish peroxidase [WGA-HRP]) in AI and AII and of retrograde tracers (WGA-HRP, fast blue, diamidino yellow, rhodamine-labeled latex beads) in areas 17 and 18. It was found that the projections are nearly completely eliminated in development, this, by the end of the first postnatal month. Until then, most of the transitory axons seem to remain confined to the white matter and the depth of layer VI; a few enter it further but do not appear to form terminal arbors. As for other transitory cortical projections the disappearance of the transitory axons seems not to involve death of their neurons of origin. In kittens older than 1 month and in normal adult cats, retrograde tracer injections restricted to, or including, areas 17 and 18 label only a few neurons in areas AI and AII. Unlike the situation in the kitten, nearly all of these are restricted to layers V and VI. A similar distribution of neurons projecting from auditory to visual areas is found in adult cats bilaterally enucleated at birth, which suggests that the postnatal elimination of the auditory-to-visual projection is independent of visual experience and more generally of information coming from the retina.

Identification and sequencing of cDNA clones encoding the granule-associated serine proteases granzymes D, E, and F of cytolytic T lymphocytes

Abstract: Cytoplasmic granules of cytolytic T lymphocytes contain at least six related serine esterases (granzymes) that are released together with perforin, a pore-forming protein related to complement component C9, during target-cell lysis. Polyclonal antibodies were used to isolate a large number of cDNA clones from an expression library derived from cytolytic-T-cell mRNA. Three distinct full-length cDNA clones coding for granzymes D, E, and F were identified by restriction site mapping and nucleotide sequencing. The three deduced amino acid sequences are highly similar to one another (between 72% and 90% amino acid identities) and to the sequences of granzymes B and C, cathepsin G, and rat mast-cell proteases I and II (between 43% and 57% amino acid identities). Cysteine residues capable of forming intramolecular disulfide bonds are conserved, as are the catalytic-site residues characteristic of serine proteases. Comparison of the cDNA-derived protein sequences with the amino termini of the isolated granzymes provides evidence that they are stored in a fully processed, activated form after removal of the signal peptide and two additional residues (propeptide) at the amino terminus. Immunoelectron microscopic studies demonstrated that granzymes D, E, and F are present in the same morphologically distinct cytoplasmic granules in which perforin has been found previously.

Enalapril for pregnancy-induced hypertension: acute renal failure in a neonate.

Abstract: Excerpt Fatal neonatal anuria has been described after administration of the angiotensin converting enzyme inhibitor Captopril during pregnancy (1, 2). Animal experiments (3) and observations in pa...

Oxidative and non-oxidative glucose metabolism in non-obese Type 2 (non-insulin-dependent) diabetic patients

Abstract: Insulin resistance is a common feature of Type 2 (non-insulin-dependent) diabetes mellitus This defect in insulin-mediated glucose metabolism could result from a defect in either glucose oxidation or non-oxidative glucose disposal To examine this question, euglycaemic insulin clamp studies were performed in 16 normal weight Type 2 and 11 age-matched control subjects In Type 2 diabetic patients the fasting plasma glucose concentration, 839 +/- 050 mmol/l, was allowed to decline (over 54 +/- 6 min) to 533 +/- 011 mmol/l before starting the insulin clamp Total body glucose uptake was significantly decreased in Type 2 diabetic patients vs control subjects (148 +/- 15 vs 264 +/- 25 mg/minm2, p less than 0001) Both total glucose oxidation (59 +/- 6 vs 89 +/- 6 mg/minm2, p less than 0005) and non-oxidative glucose disposal (89 +/- 15 vs 179 +/- 24 mg/minm2, p less than 0005) were significantly reduced in the Type 2 diabetic patients Basal glucose oxidation was also reduced in the Type 2 diabetic patients (22 +/- 3 vs 38 +/- 5 mg/minm2, p less than 001) In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal

Minor Clinical Features of Atopic Dermatitis

Abstract: The diagnostic significance of 8 previously proposed minor features of atopic dermatitis (AD) was evaluated. The minor features studied were: nipple eczema, cheilitis, Dennie-Morgan infraorbital fold,

Radioimmunotherapy of human colon carcinoma by 131I-labelled monoclonal anti-CEA antibodies in a nude mouse model.

Abstract: A mixture of 3 MAbs directed against 3 different CEA epitopes was radiolabelled with 131I and used for the treatment of a human colon carcinoma transplanted s.c. into nude mice. Intact MAbs and F(ab')2 fragments were mixed because it had been shown by autoradiography that these 2 antibody forms can penetrate into different areas of the tumor nodule. Ten days after transplantation of colon tumor T380 a single dose of 600 microCi of 131I MAbs was injected i.v. The tumor grafts were well established (as evidenced by exponential growth in untreated mice) and their size continued to increase up to 6 days after radiolabelled antibody injection. Tumor shrinking was then observed lasting for 4-12 weeks. In a control group injected with 600 microCi of 131I coupled to irrelevant monoclonal IgG, tumor growth was delayed, but no regression was observed. Tumors of mice injected with the corresponding amount of unlabelled antibodies grew like those of untreated mice. Based on measurements of the effective whole-body half-life of injected 131I, the mean radiation dose received by the animals was calculated to be 382 rads for the antibody group and 478 rads for the normal IgG controls. The genetically immunodeficient animals exhibited no increase in mortality, and only limited bone-marrow toxicity was observed. Direct measurement of radioactivity in mice dissected 1, 3 and 7 days after 131I-MAb injection showed that 25, 7.2 and 2.2% of injected dose were recovered per gram of tumor, the mean radiation dose delivered to the tumor being thus more than 5,000 rads. These experiments show that therapeutic doses of radioactivity can be selectively directed to human colon carcinoma by i.v. injection of 131I-labelled anti-CEA MAbs.

Stimulation and proliferation of CD4+ peripheral blood T lymphocytes induced by an anti-CD4 monoclonal antibody.

Abstract: There is experimental evidence that the CD4 molecule participates in the antigen-driven activation of T cells expressing this surface glycoprotein. Whether CD4, a member of the immunoglobulin supergene family, acts as a ligand-binding molecule and/or is directly involved in the activation pathway has yet to be established. In this study, we show that human CD4+ lymphocytes can be activated by exposure to the anti-CD4 monoclonal antibody (mAb) B66. Normal peripheral blood CD4+ cells were induced to proliferate and to synthesize interleukin 2 (IL 2) by the antibody. The specificity of the antibody stimulatory activity was tested by using IL 2-producing clones bearing either CD4 or CD8 on their surface. IL 2 production was induced by mAb B66 in CD4+, but not CD8+, clones, whereas both types of clones responded to stimulation by the anti-CD3 mAb Leu-4. Despite its unique stimulatory activity, mAb B66 shared with other anti-CD4 antibodies the ability to inhibit the specific cytolytic activity of CD4+ effector cells. These results clearly indicate that cross-linking of surface CD4 molecules with appropriate antibodies can fully activate CD4+ lymphocytes. Whether the natural ligand for CD4 can trigger this activation pathway remains to be defined.

Estrogen-dependent in vitro transcription from the vitellogenin promoter in liver nuclear extracts.

Abstract: One approach to analyzing the molecular mechanisms of gene expression in vivo is to reconstitute these events in cell-free systems in vitro. Although there is some evidence for tissue-specific transcription in vitro, transcriptionally active extracts that mimic a steroid hormone-dependent enhancement of transcription have not been described. In the study reported here, nuclear extracts of liver from the frog Xenopus laevis were capable of estrogen-dependent induction of a homologous vitellogenin promoter that contained the estrogen-responsive element.

The probability and severity of ruin for combinations of exponential claim amount distributions and their translations

Abstract: In the classical compound Poisson model of the collective theory of risk let ψ(u, y) denote the probability that ruin occurs and that the negative surplus at the time of ruin is less than − y. It is shown how this function, which also measures the severity of ruin, can be calculated if the claim amount distribution is a translation of a combination of exponential distributions. Furthermore, these results can be applied to a certain discrete time model.

Mathematical fun with ruin theory

Abstract: Some classical results of ruin theory are derived by probabilistic methods, which have an interest of their own. Let X1, X2, … be positive, independent and identically distributed random variables with common mean μ. Let Sk = X1 + ⋯ + Xk, x > 0 and 0 ∑ k=0 ∞ a k (S k +x) k−1 k! e−a(Sk+x) and ∑ k=0 ∞ a k (S k +x) k k! e−a(Sk+x) are surprisingly simple: the first is 1/x, and the second is 1/(1 − aμ). Another basic element is the following classical result. Let U(t) = ct − S(t) denote the difference between premiums received and claims paid by time t. Then, given that U(t) = x (i.e. that the process U crosses the level x at time t), the conditional probability that the level x has not been attained before time t is identical to the conditional probability that U has never been negative before time t, and this probability is simply x/(ct); this result can be easily obtained with a martingale argument that is due to Delbaen and Haezendonck (1985). Applications to ruin theory include the probability of ruin with no initial surplus, and the distribution H of the first surplus below the initial level. In the case of an arbitrary initial surplus, a series representation is given for the probability of ruin. If all claims are of a constant size, we get well-known expressions for the probability of ruin. Finally it is shown how the convolutions of H are related to the Sk's. In a special case the well-known formula for the convolution of uniform distributions is obtained.