Reversible choreoathetosis as the early onset of HIV-encephalopathy.
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AIDS Dementia Complex↗
Biomedical subjects
A Musso
Publications and source records attributed to A Musso.
An Italian family with Nasu-Hakola disease.
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Adult↗
Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis.
BACKGROUND: Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM: To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS: Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS: Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS: In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.
Aged↗
Proteasomes are a target of the anti-tumour drug vinblastine.
Proteasomes, the proteolytic machinery of the ubiquitin/ATP-dependent pathway, have a relevant role in many processes crucial for cell physiology and cell cycle progression. Proteasome inhibitors are used to block cell cycle progression and to induce apoptosis in certain cell lines. Here we examine whether proteasomal function is affected by the anti-tumour drug vinblastine, whose cytostatic action relies mainly on the disruption of mitotic spindle dynamics. The effects of vinblastine on the peptidase activities of human 20 S and 26 S proteasomes and on the proteolytic activity of 26 S proteasome were assessed in the presence of specific fluorogenic peptides and (125)I-lysozyme-ubiquitin conjugates respectively. The assays of ubiquitin-protein conjugates and of inhibitory kappa B alpha (I kappa B alpha), which are characteristic intracellular proteasome substrates, by Western blotting on lysates from HL60 cells incubated with or without vinblastine, illustrated the effects of vinblastine on proteasomes in vivo. We also evaluated the effects of vinblastine on the signal-induced degradation of I kappa B alpha. Vinblastine at 3--110 microM reversibly inhibited the chymotrypsin-like activity of the 20 S proteasome and the trypsin-like and peptidyl-glutamyl-peptide hydrolysing activities of both proteasomes, but only at 110 microM vinblastine was the chymotrypsin-like activity of the 26 S proteasome inhibited; furthermore, at 25--200 microM the drug inhibited the degradation of ubiquitinated lysozyme. In HL60 cells exposed for 6 h to 0.5--10 microM vinblastine, the drug-dose-related accumulation of polyubiquitinated proteins, as well as that of a high-molecular-mass form of I kappa B alpha, occurred. Moreover, vinblastine impaired the signal-induced degradation of I kappa B alpha. Cell viability throughout the test was approx. 95%. Proteasomes can be considered to be a new and additional vinblastine target.
Antineoplastic Agents, Phytogenic↗
Structural and functional characterization of 20S and 26S proteasomes from bovine brain.
Two proteins were isolated, in a stable form, from bovine brain by ion exchange chromatography, gel filtration and ultracentrifugation on glycerol gradient. They were identified as 20S and 26S proteasomes on the basis of molecular mass, migration velocity on non-denaturing gels, immunoreactivity, multipeptidase activity and the 26S proteasome also for dependence on ATP for the degradation of short peptides and ubiquitinylated proteins. However, the 26S proteasome has some properties not yet described for its counterpart of other tissues and from brain of this and other species. In particular, the ATP concentration required by the 26S proteasome to reach maximal peptidase activity was approximately 40-fold lower than the one required for maximal proteolytic activity on polyubiquitinylated substrates. Moreover, plots of substrate concentration vs. velocity gave a saturation curve for the 26S proteasome only, which, for the trypsin-like and post-glutamyl peptide hydrolase activities fitted the Michaelis-Menten equation, whereas for the chymotrypsin-like activity indicated multibinding site kinetics with positive cooperativity (n = 2.32+/-0.38). As concerns the 20S proteasome, its electrophoretic pattern on native gel revealed a single protein band, a feature, to our knowledge, not yet described for the brain particle of any species.
Animals↗
Self-expanding covered esophageal ultraflex stent for palliation of malignant colorectal anastomotic obstruction complicated by multiple fistulas.
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Adenocarcinoma↗
In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance.
BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. METHODS: Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-21-D0), participants received a placebo, and in the second (D0-D21), dexfenfluramine (30 mg/day). At D-21, D0 and D21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D2, basal PDH activity and clinical parameters were assayed. RESULTS: In both groups of participants at D0 all parameters tested were constant with respect to D-21; at D2, only basal PDH activity rose significantly; at D21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. CONCLUSION: In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.
Adult↗
Covered metal stents for management of inoperable malignant colorectal strictures.
BACKGROUND: Metal stents have been reported as an effective alternative to surgery for the palliation of patients with colorectal neoplastic obstruction. Because most of the published series describe the use of uncovered stents, the purpose of our study was to prospectively evaluate the effectiveness, feasibility, safety, and outcome of covered stents for the palliative treatment of malignant colorectal strictures. METHODS: Sixteen patients with advanced distal colorectal cancer underwent placement of 10 and 12 cm long, 23 mm diameter covered stents under fluoroscopic and endoscopic control. Clinical and endoscopic follow-up was scheduled at 3- to 6-week intervals. RESULTS: Stent insertion was successful in 15 of 16 patients (93%). Perforation occurred in one patient during stent placement requiring colostomy. Relief of bowel obstruction was documented in all successfully treated patients. The median follow-up was 21 weeks (range 1 to 46). No recurrence of obstruction was observed during the follow-up period. Stent migration occurred in 2 patients, 7 and 21 days after stent placement. CONCLUSIONS: Covered stents may provide safe and effective palliation of patients with malignant rectosigmoid strictures. Prolonged luminal patency and sealing of fistulous tracts are potential advantages of covered versus uncovered stents in the palliative treatment of colorectal malignancies. ¿
Aged↗
[Antigen detection in stools as a first choice for laboratory diagnosis of Helicobacter pylori disease].
BACKGROUND: Several techniques have been suggested for Helicobacter pylori infection diagnosis, invasive (histology) and not invasive (Urea Breath Test C13, or serological assays). An enzyme immunoassay able to detect Helicobacter pylori antigen directly in stool specimens was recently developed. A study was carried out in order to evaluate the sensibility and the specificity of this test comparing it with the Urea Breath Test C13 and histology. The patients studied are all in pediatric age, and great are the advantages of a non-invasive method to detect infection. METHODS: In this study 60 patients were enrolled. In 34 of them Helicobacter pylori infection was diagnosed by Urea Breath Test C13, all confirmed by histology. In all the 60 patients studied the fecal antigen was researched by an immunoenzymatic method (Premier Platinum HpSA, Meridian Diag.). RESULTS: The detection of Helicobacter pylori in stool shows a sensibility of 100% and a specificity of 97%. CONCLUSIONS: Sensibility and specificity, considering also the low cost of the examination, the short time to perform it and the very easy technique, allows us to propose the test as the first choice in the diagnosis of Helicobacter pylori disease.
English Abstract↗
Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance.
Crohn's disease (CD) is a condition characterized by excessive numbers of activated T cells in the mucosa. We investigated whether a defect in apoptosis could prolong T cell survival and contribute to their accumulation in the mucosa. Apoptotic, Bcl-2+, and Bax+ cells in tissue sections were detected by the TUNEL method and immunohistochemistry. T cell apoptosis was induced by IL-2 deprivation, Fas Ag ligation, and exposure to TNF-alpha and nitric oxide. TUNEL+ leukocytes were few in control, CD, and ulcerative colitis (UC) mucosa, with occasional CD68+ and myeloperoxidase+, but no CD45RO+, apoptotic cells. Compared with control and UC, CD T cells grew remarkably more in response to IL-2 and were significantly more resistant to IL-2 deprivation-induced apoptosis. CD T cells were also more resistant to Fas- and nitric oxide-mediated apoptosis, whereas TNF-alpha failed to induce cell death in all groups. Compared with control, CD mucosa contained similar numbers of Bcl-2+, but fewer Bax+, cells, while UC mucosa contained fewer Bcl-2+, but more Bax+, cells. Hence, the Bcl-2/Bax ratio was significantly higher in CD and lower in UC. These results indicate that CD may represent a disorder where the rate of T cell proliferation exceeds that of cell death. Insufficient T cell apoptosis may interfere with clonal deletion and maintenance of tolerance, and result in inappropriate T cell accumulation contributing to chronic inflammation.
Abatacept↗
Regulation of ICAM-1-mediated fibroblast-T cell reciprocal interaction: implications for modulation of gut inflammation.
BACKGROUND & AIMS: Immune-nonimmune cell interactions modulate mucosal immunity. We investigated the expression of adhesion molecules by intestinal fibroblasts, the effect of immune cell-derived factor on fibroblast binding of T cells, and the consequences of interfering with adhesion molecule expression on fibroblast-T cell interaction. METHODS: Expression of fibroblast intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 surface and messenger RNA (mRNA) was measured before and after exposure to immune cell-derived supernatants. Fibroblasts were treated with antibodies to ICAM-1 or VCAM-1, or ICAM-1 antisense oligonucleotide Isis 2302, before a T-cell adhesion assay. RESULTS: Fibroblast activation by immune cell-derived cytokines enhanced ICAM-1 and VCAM-1 surface expression and mRNA as well as adhesiveness for T cells. Blockade with neutralizing antibodies showed that binding was almost exclusively dependent on ICAM-1. Isis 2302 specifically reduced fibroblast ICAM-1 mRNA and dose-dependently inhibited ICAM-1 surface expression and T-cell binding. CONCLUSIONS: ICAM-1 is essential for intestinal fibroblast binding of T cells, a phenomenon that is efficiently and specifically disrupted by ICAM-1 antisense oligonucleotides. These observations emphasize the crucial regulatory role of fibroblasts in mucosal immunity and their potential as targets for therapeutic intervention in intestinal inflammation.
Blotting, Northern↗
Antisulfatide polyneuropathy: antibody-mediated complement attack on peripheral myelin.
Increased titers of circulating antisulfatide antibodies are consistently associated with a variety of chronic axonal and demyelinating polyneuropathy syndromes. Previous studies have shown that the pattern of antisulfatide binding to neural tissues correlates with the type of neuropathy. This suggests a possible role for antisulfatide antibodies in inducing peripheral nerve dysfunction, although their exact contribution to the pathogenesis of neuropathy is still unknown. We examined sural nerve biopsy specimens from two patients with sensorimotor and small fiber sensory neuropathy associated with high titers of IgM monoclonal antibodies to sulfatide. Electrophysiological and pathological findings were consistent with predominant demyelination in the patient with sensorimotor involvement, whereas evidence of demyelination was obtained only by teased fiber examination in the other patient. The ultrastructural study disclosed in both cases the presence of myelinated fibers with widely spaced myelin, due to a separation of leaflets of the intraperiod lines. Immunocytochemistry, performed on frozen sections, demonstrated the presence of IgM and complement product C3d bound to myelin sheaths of almost all fibers. Few fibers were immunoreactive for complement components C1q and C5. In addition, the terminal complement complex neoantigen C5b-C9, not associated with S protein, was detected on some myelinated fibers. The results suggest that, at the least in some forms of demyelinating neuropathy associated with antisulfatide antibodies, pathological changes are complement mediated. Our data further confirm previous clinical and experimental observations that complement activation initiates separation of myelin intraperiod lines.
Aged↗
[News in virology for pediatricians].
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Child↗
Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission; persistence of anti-hepatitis C virus in children is associated with the mother's anti-hepatitis C virus immunoblotting pattern.
To determine the rate of vertical transmission of hepatitis C virus (HCV), we prospectively studied 45 babies born to anti-HCV-positive women with or without concomitant infection with the human immunodeficiency virus (HIV). We performed a second-generation recombinant immunoblotting assay, alanine transaminase (ALT) evaluation, and HCV-RNA testing on sera from 27 infants of HCV+, HIV- mothers and 18 babies of HCV+, HIV+ women, at birth and thereafter. After birth, HCV antibodies progressively disappeared within 12 months in all children but one, whose mother was HCV+, HIV+; this child was the only one who showed detectable levels of HCV-RNA and abnormal ALT values throughout the follow-up (range, 12 to 27 months). Viremia was persistently negative, and ALT levels were continuously normal in the remaining infants, showing that "seronegative" infection with HCV was absent in both groups. Clearance of passively acquired anti-HCV antibodies was found to be slower among babies born to HIV+ mothers (22.3% vs. 3.8% at 12 months, P = .03) and children whose mothers showed three or four anti-HCV reactivities by immunoblotting maintained anti-HCV for longer periods compared with babies born to mothers with one or two anti-HCV reactivities (P = .0001). Seventeen of 27 babies born to HCV+, HIV- mothers were breast-fed, and none of them was infected, confirming the apparent safety for HCV of breast milk. In summary, according to our study, vertical transmission of HCV is an infrequent event, and the presence of HIV in the mother is not an important co-factor for transmission of HCV infection.
Alanine Transaminase↗
Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease: do they recognize different subsets of a heterogeneous disease?
OBJECTIVE: To evaluate the prevalence of anti-neutrophil cytoplasmic antibodies in a series of patients with inflammatory bowel disease, the discriminatory value of these antibodies in differentiating between ulcerative colitis and Crohn's disease, their antigen specificity and their correlation with epidemiological and clinical variables. METHODS: Serum anti-neutrophil cytoplasmic antibodies were evaluated by indirect immunofluorescence and immunoblotting using neutrophils isolated from peripheral blood and by enzyme-linked immunosorbent assays (ELISAs) using proteinase 3 and myeloperoxidase as antigens. RESULTS: Anti-neutrophil cytoplasmic antibodies were detected by immunofluorescence in 43 (39.8%) of 108 patients with ulcerative colitis, in 11 (11.9%) of 92 patients with Crohn's disease (P < 0.001) and 5 (6.8%) of 73 control patients. The predominant pattern was perinuclear staining around neutrophil nuclei (44 of 59, 75%); a homogeneous cytoplasmic staining was present in 15 (25%) of 59 sera, mainly among Crohn's disease and control patients. The ELISAs gave no positive results. Recognition of proteins of relative molecular masses 27,000 and 49,000 at immunoblotting was common to ulcerative colitis, Crohn's disease and control sera. The proteins of relative molecular masses 32,000 and 106,000 were recognized exclusively by 11% of anti-neutrophil-positive ulcerative colitis sera. No significant correlation was found between the presence of anti-neutrophil cytoplasmic antibodies and the demographic and clinical characteristics of the patients. CONCLUSION: Anti-neutrophil cytoplasmic antibodies are detectable in a large proportion of patients with ulcerative colitis, but their prevalence in a limited proportion of patients with Crohn's disease reduces their discriminatory capability. The persistence of anti-neutrophil cytoplasmic antibodies after total colectomy and the absence of a correlation between the activity of the disease and the presence or titre of these antibodies support the hypothesis that anti-neutrophil cytoplasmic antibodies are not simply an epiphenomenon of colonic inflammation.
Adult↗
Total lymphoid irradiation for treatment of drug resistant chronic GVHD.
We report our experience with total lymphoid irradiation (TLI) in three patients with GVHD which had failed to respond to standard drug treatment. The clinical manifestations of GVHD markedly improved with TLI treatment.
Adolescent↗
[Long lasting conjunctivitis: research of etiological factors].
Forty children with long-lasting or recurrent conjunctivitis were included in this etiological study. It is well known that purulent conjunctivitis is mainly bacterial, with a major source of infection from Chlamydia; recently, however, a greater percentage of viral forms, with the exception of conjunctivitis without secretion, has been reported. The authors focused their attention on the clinical symptoms and on bacteriological studies of the forms of Chlamydia and Mycoplasma conjunctivitis, highlighting their marked sensitivity to antibiotics and the clinical response and recommending the importance of an etiological study in all cases in which conjunctivitis does not resolve within a short period of time.
Child↗
Evaluation of thermal biofeedback treatment of hypertension using 24-hr ambulatory blood pressure monitoring.
Ten male hypertensives, whose BPs were controlled on a combination of sympatholytic and diuretic medications, were given 16 sessions of thermal biofeedback prior to attempting withdrawal from the sympatholytic drug. Results were evaluated using 24-hr ambulatory BP monitoring (ABPM) as well as clinic and home BPs, both in multi-baseline-across-subject designs and as a single group. Results showed significant treatment effects on 24-hr ABPM data, both at the individual level (SBPs only) and in the aggregate analyses (SBP and DBP). BPs assessed in the clinic by random zero sphygmomanometer and patient-assessed home BPs were also reduced.
Aged↗