Operational equivalence between segmental and whole-body bioelectrical impedance in renal patients.
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Body Composition↗
Biomedical subjects
B Rossi
Publications and source records attributed to B Rossi.
Selective techniques of apheresis in polyneuropathy associated with monoclonal gammopathy of undetermined significance.
Three cases affected by peripheral neuropathy associated to monoclonal gammopathy of undetermined significance (MGUS) were treated by using selective apheretic techniques, chosen on the basis of the serological characteristics of the gammopathy. Double filtration plasmapheresis was used in the first two cases, respectively affected by gammopathy of IgM type, kappa chains, and IgG type, lambda chains; protein A immunoadsorption in Case 3 with IgG type, lambda chains. Apheretic sessions were performed for three-four months, in association with low-dose immunosuppressive therapy. Clear and stable improvement of the neuropathy over 12-month follow-up period was observed both from a clinical and electrophysiological point of view. It is concluded that in peripheral neuropathy associated with MGUS selective techniques of apheresis can prove useful both in obtaining positive results and in avoiding the collateral effect of the original plasma exchange.
Adult↗
SOD1 missense mutation in an Italian family with ALS.
We have discovered a new Italian pedigree with autosomal-dominant ALS. The pedigree, at present, comprises 75 members distributed in five generations. ALS was diagnosed in eight patients. The mean +/- SD age of onset of the disease was 46.8 +/- 13.5 years, with a range of 29 to 63 years. The mean +/- SD duration of the disease was 11.6 +/- 1.7 months. Molecular genetic studies showed a missense mutation (Gly-->Ser, codon 41) in exon 2 of the Cu/Zn superoxide dismutase gene (SOD1) on chromosome 21 in the available affected member and in 45% of the at-risk subjects of the pedigree. This study confirms the presence of SOD1 point mutations in families with autosomal-dominant ALS and suggests that additional genetic or environmental factors may be involved in the full expression of the disease.
Adult↗
High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.
Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.
CD3 Complex↗
High overhead? Here's what to do about it!
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Capital Expenditures↗
Relationship between increased blood pressure and hypoalgesia: additional evidence for the existence of an abnormality of pain perception in arterial hypertension in humans.
An association between hypertension and decreased pain perception (hypoalgesia) has been shown in experimental hypertension and confirmed in humans by electrical tooth pulp stimulation. The aim of this study was to confirm, using two other techniques, whether hypertension is associated with hypoalgesia in humans. In 77 untreated essential hypertensive outpatients, 37 normotensive outpatients and 27 normotensive volunteers subjective cutaneous sensitivity was assessed by an electrical stimulator. Thirty-three measurements were repeated after one month. In addition, in eight normotensive volunteers and eight hypertensives the thresholds of the polysynaptic components R2 and R3 of the blink reflex to electrical stimulation of the supraorbitalis nerve were evaluated. Tooth pulp stimulation was done in 85 of the subjects who measured cutaneous sensitivity and in all of the blink reflex study. Cutaneous perceptive, pain and tolerance thresholds were significantly higher in the hypertensives compared with both normotensive groups, with no significant difference between these two. The results were identical when age and sex-matched subgroups were compared and a high reproducibility was found for all three parameters. Similar findings were obtained for the tooth pulp thresholds and highly statistically significant correlations were found between cutaneous and tooth pulp sensitivity and between these indices and blood pressure. The thresholds of R2 and R3 were also significantly higher in the hypertensives and a significant correlation was found between R3 threshold and diastolic pressure. These results confirm that hypertension is associated to hypoalgesia in humans.
Adult↗
Expression of decay-accelerating factor (CD55) of the complement system on human spermatozoa.
Human spermatozoa were analyzed for their expression of decay-accelerating factor (DAF, CD55), a glycolipid-anchored regulatory protein of the C casade. Morphologic data showed that DAF was localized at the acrosomal region of the sperm head. Analysis with anti-DAF antibody-immunoprecipitated proteins of acrosome-reached spermatozoa revealed a 44- to 54-kDa protein. Carbohydrate analysis of sperm DAF indicated that it contains nonsialated N- and O-linked sugars. The absence of mature oligosaccharides on this protein appears to account for the difference in molecular mass between sperm DAF and the 70-kDa DAF expressed on other human tissues. Sperm DAF reinserted into sheep E and inhibited C-mediated lysis. This effect was reversed by mAb, which block DAF function. These results indicate that sperm DAF also possesses a glycolipid anchor. The expression of DAF on acrosome-reacted spermatozoa suggests that it may act concomitantly with other C regulators such as membrane cofactor protein to modulate the activation of C in the immunocompetent female genital tract and protect acrosome-reacted spermatozoa from C-mediated attack.
Acrosome↗
Disruption of microtubule network in human monocytes induces expression of interleukin-1 but not that of interleukin-6 nor tumor necrosis factor-alpha. Involvement of protein kinase A stimulation.
We have reported recently that colchicine and other microtubule-disrupting agents stimulated interleukin-1 (IL-1) alpha and beta synthesis in human monocytes. In this study we found that unexpectedly colchicine failed to stimulate the expression of two other potent immune mediators, namely tumor necrosis factor-alpha and interleukin-6. Remarkably, taxol which induces stable microtubule bundles, antagonized the colchicine but not the LPS-induced IL-1 synthesis. These results suggested that the colchicine-mediated IL-1 induction was generated by microtubule disassembly. We next demonstrated that microtubule disruption triggered an elevation of intracellular levels of cAMP and a subsequent stimulation of protein kinase A. The use of different protein kinase inhibitors supported a role of the PKA, but not the PKC, in the colchicine-induced IL-1 production. Furthermore, elevation of intracellular cAMP levels by 8-bromo-cAMP, forskolin, or cholera toxin potentiated the effect of suboptimal concentration of colchicine on IL-1 synthesis. However, these agents alone were unable to induce IL-1 synthesis. Therefore, our data indicate that the cAMP/protein kinase A-signaling pathway is necessary but not sufficient to generate IL-1 synthesis by microtubule disruption. Thus, microtubule-disrupting drugs appear as useful tools to further characterize the molecular events which regulate IL-1 production in human monocytes.
Adenylyl Cyclases↗
Characterization and purification of T lymphocyte aminopeptidase B: a putative marker of T cell activation.
We have previously described that human T lymphocytes express membrane-associated peptidase activities (Mari et al., EMBO J., 1992, 11:3875). We show in this report that intact Jurkat T cells readily cleaved H-Arg-paranitroanilide, an aminopeptidase B (AP-B) substrate. The identification of the hydrolyzing activity as AP-B was confirmed by its sensitivity to both arphamenine B and bestatin in the nanomolar range. Significant AP-B activity was released in the supernatant upon incubation of intact T lymphocytes at 37 degrees C. However, AP-B activity was found mainly in the cytosolic fraction of Jurkat T cells. Cytosolic T cell AP-B was purified to homogeneity and exhibited a molecular mass of 72 kDa. Purified AP-B cleaved N-terminal basic amino acid-containing peptides such as thymopentin (H-Arg-Lys-Asp-Val-Tyr-OH), indicating that it might play a role in the regulation of the concentration of important soluble mediators of T cell activation. A rabbit polyclonal antibody was shown to recognize AP-B as assessed by both immunoprecipitation and Western blot experiments. Finally, we found that AP-B was up-regulated during activation of normal and leukemic T lymphocytes.
Aminopeptidases↗
Characterization of a cDNA clone coding for human testis membrane cofactor protein (MCP, CD46).
Membrane cofactor protein (MCP) is a complement regulatory protein that acts as a cofactor for the cleavage of C3b and C4b by the serine protease factor I. We have previously reported the characterization of a functional MCP molecule on the acrosomal membrane. This protein migrated as a single band with a molecular weight of 40,000 Da, which is 10,000-20,000 Da smaller than the known MCP molecules, and is devoid of N- and O-linked sugars. We have proposed that the difference in molecular weight resulted from the lack of sugars. To investigate if this is due to the absence of glycosylation sites, we have characterized a cDNA clone from a human testis cDNA library. This cDNA corresponds to a peculiar MCP form previously described, which is characterized by the presence of the serine/threonine/proline-rich exon C (STPC) and the cytoplasmic tail known as CYT2, and we conclude that the absence of mature oligosaccharide of the sperm MCP cannot be totally attributed to a defect of N- and O-glycosylation sequences but rather reflects an alteration of the mechanisms of glycosylation in spermatozoa. The presence of functional MCP on the acrosomal membrane, as well as the other complement regulatory protein, decay-accelerating factor, strongly suggests that these proteins may act concomitantly to protect the acrosome-reacted spermatozoa from the attack of the complement present in the female genital tract.
Amino Acid Sequence↗
Methodological considerations on the use of the blink reflex R3 component in the assessment of pain in man.
We define the principal physiological properties of the nociceptive component R3 of the blink reflex (b.r.) on electrical stimulation of the supraorbital nerve, with the aim of supplying some rules for its use in the analysis of pain in man. We explore the relationship between the threshold (th) of R3 and that of pain on stimulation of the trigeminal nerve and the extent to which R3 is modulated by habituation and attentional levels. Both pain th and R3 th correlate significantly with age. The R3 th was always higher than the R2 th. Habituation definitely decreases the amplitude of R3, which easily disappears. Focusing of attention on the stimulus sharply inhibits R3 while distraction increases it. Our findings emphasize the need to take all these aspects into account when designing protocols for the study of pain mechanisms based on the R3 reflex component.
Adolescent↗
Management of bowel obstruction in advanced and terminal cancer patients.
BACKGROUND: Bowel obstruction is a common and distressing outcome in patients with abdominal or pelvic cancer. PATIENTS AND METHOD: Patients may develop bowel obstruction at any time in their clinical history, with an incidence ranging from 5.5% to 42% in ovarian carcinoma and from 10% to 28.4% in colorectal cancer. The causes of the obstruction may be benign postoperative adhesions, a focal malignant or benign deposit, relapse or diffuse carcinomatosis. The symptoms which are almost always present are intestinal colic (reported in 72%-76% of patients), abdominal pain due to distension, hepatomegaly or tumor masses (in 92% of patients) and vomiting (68%-100%) of cases. CONCLUSION: While surgery must remain the primary treatment for malignant obstruction, it is now recognised that there is a group of patients with advanced disease or poor general condition who are unfit for surgery and require alternative management to relieve distressing symptoms. A number of treatment options are now available for the patient with advanced cancer who develops intestinal obstruction. In this review of the literature, the indications for surgery will be examined, the use of nasogastric tube and percutaneous gastrostomy evaluated and the place of drugs for symptom control described.
Abdominal Neoplasms↗
Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.
A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding to host cells was previously used to characterize a 57- to 67-kDa cell surface glycoprotein as a potential MV receptor. In the present work, this glycoprotein (gp57/67) was immunopurified, and N-terminal amino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene cluster. Transfection of nonpermissive murine cells with a recombinant expression vector containing CD46 cDNA conferred three major properties expected of cells permissive to MV infection. First, expression of CD46 enabled MV to bind to murine cells. Second, the CD46-expressing murine cells were able to undergo cell-cell fusion when both MV hemagglutinin and MV fusion glycoproteins were expressed after infection with a vaccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD46 murine B cells were able to support MV replication, as shown by production of infectious virus and by cell biosynthesis of viral hemagglutinin after metabolic labeling of infected cells with [35S]methionine. These results show that the human CD46 molecule serves as an MV receptor allowing virus-cell binding, fusion, and viral replication and open new perspectives in the study of MV pathogenesis.
Amino Acid Sequence↗
Evoked potentials in the evaluation of patients with mitochondrial myopathy.
Multimodality evoked potentials and pattern electroretinograms (PERGs) were performed in seventeen patients with histologically defined mitochondrial myopathy (MM). Brainstem auditory evoked potentials showed abnormalities in 47% and somatosensory evoked potentials in 76%. Visual evoked potentials were outside the normal range in 71%; PERGs exhibited a decreased amplitude or delayed P50 in 78%. These findings may be considered as an expression of impairment of the central nervous system in MM, even if the specific mechanism, 'structural' or 'functional', needs further investigation.
Adolescent↗
Overhead control.
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Capital Expenditures↗
Regulation of phospholipid metabolism by K+ channel blockers and inhibitors of choline transport in the Jurkat T cell line. Relationships with cell proliferation and interleukin-2 production.
In the human T cell line Jurkat, three drugs generally used as effectors of K+ channels, i.e., quinine, 4-aminopyridine and tetraethylammonium, modify phospholipid metabolism. The drugs inhibited the synthesis of both phosphatidylcholine and phosphatidylethanolamine. The mechanism of such inhibition involves a decreased uptake of choline and ethanolamine by the cells, since the three K+ channel blockers were found to be able to competitively inhibit the high-affinity choline/ethanolamine transport system at the membrane level. In contrast, choline transport-inhibitors such as hemicholinium-3, decamethonium and dodecyltrimethylammonium do not inhibit interleukin-2 synthesis and proliferation of the Jurkat T cell line. This indicates that the inhibition of either phosphatidylcholine and/or phosphatidylethanolamine synthesis is not directly implicated in these processes. The inhibition of interleukin-2 synthesis appeared to be mediated through the inhibition of diacylglycerol production induced by T cell activators. A major role for phosphatidylserine in the regulation of T cell activation emerged, since we demonstrated that a panel of K+ channel blockers enhanced the synthesis of this phospholipid mimicking the previously described effect of exogenously added phosphatidylserine in Jurkat cells, i.e., a blockade of interleukin-2 synthesis probably due to a defect in diacylglycerol production.
4-Aminopyridine↗
Cisapride improves gallbladder kinetics in patients affected with myotonic muscular dystrophy.
Smooth muscle involvement is relatively common in myotonic muscular dystrophy (MMD). The effects of cisapride on gallbladder motor function in myotonic patients have been investigated in 10 alithiasic patients and in 10 healthy volunteers. Gallbladder volumes were measured by ultrasonography in fasting state and 15, 30, 45 and 60 min after milk intake. The patients were treated with cisapride for two months, after which they underwent a second ultrasonographic examination. Gallbladder emptying was slower and less effective in dystrophic patients than in healthy volunteers. Cisapride was found to improve gallbladder kinetics (efficacy of contraction and rate of emptying) in patients affected with myotonic muscular dystrophy.
Adult↗
N-linked oligosaccharide chains of the insulin receptor beta subunit are essential for transmembrane signaling.
Insulin receptor (IR) is a glycoprotein possessing N-linked oligosaccharide side chains on both alpha and beta subunits. The present study focuses for the first time on the potential contribution of N-linked oligosaccharides of the beta subunit in the processing, structure, and function of the insulin receptor. To investigate this point, a receptor mutant (IR beta N1234) was obtained by stable transfection into Chinese hamster ovary cells of an IR cDNA modified by site-directed mutagenesis on the four potential N-glycosylation sites (Asn-X-Ser/Thr) of the beta subunit. The mutated receptor presents an alpha subunit of 135 kDa, indistinguishable from the wild type alpha subunit, but the beta subunit has a reduced molecular mass (80 kDa instead of 95 kDa) most likely due to the absence of N-glycosylation. Metabolic labeling experiments indicate a normal processing and maturation of this mutated receptor which is normally expressed at the surface of the cells as demonstrated by indirect immunofluorescence. The affinity of the mutant for insulin (Kd = 0.12 nM) is similar to that of the wild type receptor (Kd = 0.12 nM). However, a major defect of the mutated IR tyrosine kinase was assessed both in vitro and in vivo by (i) the absence of insulin-stimulated phosphorylation of the poly(Glu-Tyr) substrate in vitro; (ii) the reduction of the insulin maximal stimulation of the mutated IR autophosphorylation in vitro (2-fold stimulation for the mutant receptor as compared to a 7-fold stimulation for the wild type); and (iii) a more complex alteration of the mutated receptor tyrosine autophosphorylation in vivo (3-fold increase of the basal phosphorylation and a 4-fold simulation of this phosphorylation as compared to the wild type receptor, the phosphorylation of which is stimulated 14-fold by insulin). The physiological consequences of this defect were tested on three classical insulin cellular actions; in Chinese hamster ovary IR beta N1234, glucose transport, glycogen synthesis, and DNA synthesis were all unable to be stimulated by insulin indicating the absence of insulin transduction through this mutated receptor. These data provide the first direct evidence for a critical role of oligosaccharide side chains of the beta subunit in the molecular events responsible for the IR enzymatic activation and signal transduction.
Amino Acid Sequence↗