Showing papers by "University of Modena and Reggio Emilia published in 1995"

Defective brain and muscle energy metabolism shown by in vivo 31P magnetic resonance spectroscopy in nonaffected carriers of 11778 mtDNA mutation.

Abstract: In vivo phosphorus magnetic resonance spectroscopy ( 31 P-MRS) showed defective brain and muscle energy metabolism in three affected siblings in a family with Leber9s hereditary optic neuropathy (LHON) with the 11778 mtDNA mutation. We studied 14 nonaffected members of the same pedigree by 31 P-MRS and molecular genetics. Nine of 14 individuals studied had the 11778 mtDNA mutation, with various degrees of heteroplasmy. A decreased brain energy reserve, as shown by low phosphocreatine content and phosphorylation potential and high [ADP], was present in eight of these nine subjects with the 11778 mutation. A low rate of postexercise phosphocreatine recovery in muscle was present in six of the nine mutated individuals. Normal MRS findings in the brain of one and the muscle of three carriers were accompanied by a low percentage of mutated mtDNA. All subjects without mutation had normal brain and muscle MRS. 31 P-MRS disclosed defective bioenergetics in the brain or muscle or both of all asymptomatic carriers studied from our pedigree.

Invertebrate and Vertebrate Immune Cells Express Pro-opiomelanocortin (POMC) mRNA

Abstract: We show here that hemocytes and leukocytes with phagocytic activity from both invertebrates ( Planorbarius corneus, Viviparus ater ) and vertebrates ( Carassius auratus, Rana esculenta ) express pro-opiomelanocortin (POMC) mRNA, as assessed by in situ hybridization with a digoxigenin-labeled human DNA probe. These data are in accord with previous observations from our laboratories on the presence in these cells of POMC-derived peptides and strongly suggest that these molecules-highly conserved throughout evolution-play an important role in cell locomotion and phagocytosis. POMC mRNA was also detected in lymphocytes of R. esculenta, but not of C. auratus, suggesting that from anuran amphibians onwards lymphocytes also express this gene. This phenomenon could be related to the appearance of more than one immunoglobulin isotype in anurans.

Heterogeneous Distribution of Calcite Cement at the Outcrop Scale in Tertiary Sandstones, Northern Apennines, Italy

Abstract: Calcite cement derived intraformationally in seven stratigraphic units of marine origin (five submarine-fan deposits and two shelf deposits) is distributed heterogeneously at the outcrop scale. Sandstone beds intercalated with calcareous shale older than Pliocene tend to be completely cemented, whereas stacked sandstone beds that lack shale interbeds have calcite cement in the form of tightly cemented concretions that make up only 10-30% of a bed. The abundance and distribution of concretions, with few exceptions, are irregular and unpredictable. Concretion shapes include spheres (<1 m diameter), oblate and prolate spheroids (<1.5 m), tabular forms (to 8 m long), and irregular forms. Patterns of concretions within beds are remarkably varied and include both random and uniform spacing; preference for either the top, middle, or bottom of beds; preference for faults that cut bedding at a high angle; and localization around shale rip-up clasts. There is no preference of concretions for shell-rich layers. Some formations have cement patterns specific to that formation, whereas other formations have different patterns at different outcrops. Most formations have more than one cement pattern in an outcrop. The lack of strong textural (grain size, graded bedding) or compositional controls on the localization of calcite cement suggests the preeminence of highly localized hydrologic factors in determining the spatial distribution of authigenic pore-filling calcite. Spherical concretions grew by diffusive supply of intraformationally derived components, whereas prolate and elongate concretions grew chiefly under the influence of advective supply. Faults apparently served as fluid conduits and were selectively cemented. In general, only sandstones intercalated with shale are totally cemented. This indicates that shales were a major source of cement components for these sandstones at least.

7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys

Abstract: We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.

Gustatory detection thresholds after parabrachial nuclei lesions in rats.

Abstract: Rats with either electrolytic (Experiment 1) or excitotoxic lesions (Experiment 2) that had been electrophysiologically centered in the gustatory zone of the parabrachial nuclei (PBN) were tested for sucrose and NaCl taste detection thresholds in a conditioned avoidance task. With 1 exception, all of these rats had previously shown severe deficits in acquiring an LiCl-based conditioned taste aversion (CTA) to sucrose, NaCl, or alanine. The rats with excitotoxic lesions also had failed to express a depletion-induced sodium appetite. Despite the uniformity of these deficits, the rats with lesions exhibited varied performance in the detectability task. Roughly 1/3 of the rats did not perform competently, 1/3 had elevated thresholds, and 1/3 showed no or only marginal impairments in taste detectability. These findings demonstrate that the elimination of CTA following PBN lesions is not necessarily linked to an impairment in taste signal detection. Thus, PBN-induced deficits on 1 taste-related task do not entirely correspond with impairments on another.

Effects of Different Phenotypes of Hyperlipoproteinemia and of Treatment With Fibric Acid Derivatives on the Rates of Cholesterol 7α-Hydroxylation in Humans

Abstract: Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7α-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7α-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7α-3H]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82±0.22 mmol/d in the familial hypercholesterolemia group and 1.30±0.47 mmol/d in the familial combined hyperlipidemia group ( P <.05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P =NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA). Treatment with both gemfibrozil and bezafibrate reduced serum cholesterol, slightly increased HDL cholesterol, and significantly reduced serum triglyceride and apo B concentrations. Cholesterol 7α-hydroxylation rates were significantly reduced by nearly 55% both after gemfibrozil and after bezafibrate. Our findings indirectly suggest that cholesterol degradation to bile acid is independent of receptor-mediated uptake of LDL by the liver. Hydroxylation rates seem to parallel serum levels of triglyceride and apo B (particularly after fibrate treatment), possibly suggesting a coordinate regulation of bile acid and lipoprotein synthesis.

Right hemisphere developmental learning disability: A case study

Abstract: We report a case study of a 22-year-old man with a developmental learining disorder consisting of arithmetic diffcultles, visuo-spatial deficits and emotional difficulties. Language abillties and verbal learning were remarkably spared. The clinical picture was consistent with the diagnosis of ‘Right Hemisphere Developmental learning Disabillty’ (RHDLD) as described by Weintraub and Mesulam (Archives of neurology 1983; 40: 463-8). Computed tomography and magnetic resonance imaging scans were normal, but a positron emission tomography scan revealed a marked hypometabolism of the right hemisphere, supporting the claim that RHDLD is Indeed associated with functional abnormalities of the right hemisphere.

Lack of selective Vβ deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T-cell repertoire during acute HIV syndrome

Abstract: OBJECTIVE: To study the V beta T-cell repertoire in peripheral blood lymphocytes (PBL) during acute HIV syndrome by using several anti-V beta monoclonal antibodies (MAb) and to analyse its functionality by stimulating PBL with superantigens (SAg) such as Staphylococcus aureus enterotoxins. METHODS: Cytofluorimetric analysis of V beta T-cell-receptor expression was performed on PBL from eight patients with symptomatic, acute HIV-1 primary infection, showing a dramatic decrease of CD4+ PBL accompanied by a marked increase in activated/memory CD8+ T cells, and on 12 age- and sex-matched healthy controls. PBL were then isolated, stimulated with different SAg, anti-CD3 MAb or phytohaemagglutinin and cultured for 3 days. PBL capability to progress through cell cycle was studied by the classic cytofluorimetric method of bromodeoxyuridine incorporation and DNA staining with propidium iodide. RESULTS: Despite the presence of a few expansions of some V beta families among CD8+ T lymphocytes, no gross alterations in T-cell repertoire were present in patients with acute HIV syndrome. Its functionality was maintained overall, as PBL responsiveness to SAg was well preserved. Interestingly, all CD8+ T cells, although bearing different V beta T-cell receptors, expressed marked signs of activation, i.e., CD45R0, CD38 and major histocompatibility complex class II molecules, and also high amounts of CD11a and CD18. CONCLUSIONS: Our data suggest, at least in the early phases and in the acute form of the infection, that HIV is not likely to act as a SAg. However, further studies are needed to analyse other sites, such as lymph nodes, where HIV could exert other, significant effects, and to study the expression of other V beta families than those investigated here.

A randomized, double-blind, cross-over study comparing a levosulpiride-based and a metoclopramide-based combination in the prevention of promece-cytabom-induced emesis

Abstract: BACKGROUND To test two different antiemetic regimens for preventing nausea and vomiting in patient with non-Hodgkin's lymphoma (NHL) undergoing systemic chemotherapy (CT) with ProMECE-CytaBOM (P-C) PATIENTS AND METHODS Twenty consecutive untreated adult outpatients with histologically confirmed NHL and scheduled to receive P-C chemotherapy were registered in a randomized, double-blind, cross-over study to compare the antiemetic efficacy of a levosulpiride (LS)-based and metoclopramide (MTC)-based regimen RESULTS Complete protection from vomiting was recorded in 93% (62/67) of courses with the LS-regimen and in 89% (62/70) with the MTC-regimen (p = 0428) No nausea was observed in 84% (56/67) of courses with the LS-regimen and in 74% (52/70) with the MTC-regimen (p = 0183) No differences in prevention of emesis were recorded when patients crossed to the other regimen Both regimens were well tolerated; however, on day 8 of chemotherapy, when both antiemetic regimens were administered at a higher dose, the LS-based combination showed significantly lower toxicity (p = 0035) CONCLUSIONS ProMECE-CytaBOM-induced emesis can be prevented in most cases with appropriate, specifically designed antiemetic therapy Both the LS- and MTC-based combinations resulted in a high percentage of complete protection from emesis, but the higher incidence of side effects observed with MTC makes the LS-based regimen preferable for patients receiving P-C chemotherapy

Cutaneous metastasis of chordoma.

Abstract: A chordoma metastatic to the skin of the nose is reported. The patient (a 40-year-old man) had undergone excision of a sacral chordoma 16 months previously. In patients whose clinical histories are unknown, cutaneous metastases of chordoma can be confused with mixed tumors of sweat glands. Cytological features, including the presence of physaliphorous cells, and immunohistochemical coexpression of low molecular weight keratins and S-100 protein are helpful features that lead to a correct diagnosis.

Absence of the absolutely continuous spectrum for Stark-Bloch operators with strongly singular periodic potentials

Abstract: We prove the absence of the absolutely continuous spectrum for the operator -(d2/dx2)+ Sigma j epsilon z alpha delta '(x-j)+fx, f>0 and alpha not=0 by means of the crystal momentum representation and the Howland's criterion for Floquet-type operators.

Long-term follow-up of hepatitis C virus (HCV) infection in liver transplant patients

Abstract: Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT) To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long-term outcome of 22 patients with end-stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post-OLT liver disease For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme-linked immuno-assays and by recombinant immuno-blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers) Of the 16 pre-OLT antiHCV-positive patients, 14 (875%) had recurrence of HCV infection while 2 cleared HCV Pre-OLT genotype recurred in 11 of these 14 patients (2 genotype I) 8 genotype II - in 1 case associated with genotype III - and 1 genotype IV) Of the 6 pre-OLT antiHCV-negative patients, only 1 (166%) became persistently HCV-infected, with genotypes I and II The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared

Effects of thymostimulin with combination chemotherapy in patients with aggressive non-Hodgkin's lymphoma. A report from the Italian Lymphoma Study Group (GISL).

Abstract: The purpose of this study was to test the efficacy and safety of thymostimulin (TS) administered in addition to conventional chemotherapy in patients with intermediate- and high-grade non-Hodgkin's lymphoma (IG, HG-NHL). A total of 150 patients with newly diagnosed IG- or HG-NHL were entered in a multicenter trial to compare the effectiveness of two different third-generation regimens (MACOP-B versus ProMACE-CytaBOM) and were randomized to receive chemotherapy (CT) alone or CT + TS. In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin. TS was administered i.m. at a dose of 1 mg/kg daily on days 22-28 of each drug course to patients treated with ProMACE-CytaBOM, and on days 22-29, 50-57, and 77-85 to patients treated with MACOP-B. There were 134 fully evaluable patients: 68 treated with CT alone and 66 treated with CT + TS. Patients treated with CT + TS had a higher complete remission (CR) rate compared to patients given CT alone (59.1% vs 42.4%; P = .05). CR were significantly higher for patients treated with CT + TS in the groups with IG-NHL (P = .01), in those aged less than 60 years (P = .05), with good performance status (P = .05), and normal hemoglobin levels (P = .05). Four-year survival rates are 64.5% for patients treated with CT + TS and 43.0% for those treated with CT alone (P = .30). No difference between the two treatment arms have been observed as regards drug-related toxicity and the number and severity of infectious episodes. The use of TS during the 7 days before chemotherapy has been associated with a significantly superior CR rate. The advantage of CT + TS was mostly obtained in patients with IG-NHL, and those with good performance status or normal hemoglobin levels. In these patients TS may have potentiated the host reactions against the tumor, leading to an increase in NK activity and the production of cytokines. This postulated increase in the effectiveness of chemotherapy after TS might also explain the absence of the expected myeloprotective action.

HCV and monoclonal gammopathies.

Abstract: Objective. To determine the prevalence of antibodies against HCV in monoclonal gammopathies with and without cryoglobulinemic activity. Methods. 201 patients were divided into two groups : (I)94 patients with monoclonal gammopathies with cryoglobulinemic activity, and (II) 107 with monoclonal gammopathies without cryoglobulinemic activity. Cryoglobulins were characterized by immunofixation ; HCVAb were detected using second-generation ELISA and RIBA methods ; in 38 cases the presence of HCV in peripheral blood mononuclear cells was evaluated by PCR. Results. The HCVAb prevalence, as evaluated by RIBA, in Group I was 69.1% while in Group II it was only 14.9%. Histological and immunohistochemical study of the bone marrow in Group I patients frequently showed signs of nodular B-cell clonal expansion. Conclusions. Our data confirm the existence of a close correlation between HCV infection and the monoclonal gammopathies with cryoglobulinemic activity. HCV-positive cryoglobulinemia is characterized by self-limiting IgM monoclonal expansion associated with histological aspects of bone marrow lymphoid nodules that do not expand in the course of the disease like classic evolving lymphoproliferative processes.

Hot electron luminescence in In0.53Ga0.47As transistor channel

Abstract: Measurements of light emission are reported in the 1.1–2.5 eV energy range, by hot electrons in the In0.53Ga0.47As channel of a complementary charge injection transistor. By comparing electrical characteristics and light emission, there is the ability to identify the intraconduction band transitions as the main light emission mechanism. Hot‐electron effective temperatures up to 2200 K have been determined from high energy exponential tails of the electroluminescence spectra.

Regulation of bile acid synthesis in humans : studies on cholesterol 7 α-hydroxylation in vivo

Abstract: Over the last few years important progress has been made on the quantitation of cholesterol 7α-hydroxylation, the rate-limiting step of bile acid synthesis. The use of a technique based on the determination of body water tritium enrichment after i.v. administration of [7α- 3 H] cholesterol has allowed in vivo investigation of this step in humans in different experimental conditions. The cholesterol 7α-hydroxylation rate was not affected by the administration of the hydrophilic bile acid ursodeoxycholic acid (UDCA) whereas it was significantly reduced by the more hydrophobic chenodeoxycholic acid (CDCA) and even more so by the strongly hydrophobic deoxycholic acid (DCA). The administration of cholestyramine induced a significant dose-related increase of 7α-hydroxylation along with a correspondent decrease in plasma cholesterol. The administration of simvastatin exerted no effect on cholesterol 7α-hydroxylation despite a marked decrease in serum cholesterol. Treatment with fibrates reduced plasma lipid levels and 7α-hydroxylation rates. Hydroxylation rates were unchanged in familial hypercholesterolaemia and increased in familial combined hyperlipidaemia. These data suggest that in humans bile acid synthesis can be affected by quantitative and qualitative alterations of the enterohepatic circulation of bile acids. Changes in cholesterol 7α-hydroxylation rates may be associated with alterations in plasma lipid levels, but such a relationship is ill-defined and seems to vary with the different experimental models.

In vitro infection of human epidermal Langerhans cells with human immunodeficiency virus type 1.

Abstract: Members of the dendritic cell (DC) lineage, including Langerhans cells (LC) of squamous epithelia and peripheral blood (PB) DC, have been suggested to play an important role in the pathogenesis of HIV-1 infection1. PB DC from HIV-1 infected patients contain significant amounts of HIV-1 proviral DNA and can show viral budding1. Human epidermal LC express CD4 molecules on their membrane and are thus a likely target of HIV infection. We have demonstrated that purified preparations of epidermal LC, but not other epidermal cell (EC) types, harbor HIV-1 proviral DNA and RNA, indicating that LC are productively infected and can serve as a reservoir of the virus2,3. Moreover, the HIV DNA copy number in LC of AIDS patients is comparable to that found in PB CD4+ T cells of patients at the same disease stage3. PB DC from healthy seronegative donors have been infected in vitro with HIV and could transmit the infection to other cells of myeloid origin4. Few studies have addressed the in vitro infection of epidermal LC. LC possess membrane gpl20-binding sites5; in addition, Berger and co-workers have been able to infect in vitro both LC histiocytosis cells and LC-enriched EC, but the nature of the EC type infected could not be determined6.

[Signs of inflammatory activity in thoracic sarcoidosis. A high-resolution computerized tomography study].

Abstract: Sarcoidosis is characterized by the presence of non-caseating granulomas. Lymphadenopathy and diffuse parenchymal abnormalities often involve the chest. This study was aimed at finding out signs that could be suggestive of disease activity and if the lesions are reversible after therapy. Sixty-three patients underwent chest radiography, high resolution CT, functional studies, bronchoalveolar lavage and 67Ga scintigraphy. Twenty-three patients were followed-up. Lymphadenopathies, nodular opacities and acinar opacities resolved after steroid therapy; bronchiolectasies, bronchiectasies, septal thickening and parenchymal distorsion did not disappeared after therapy and are therefore considered as irreversible lesions. Ground glass opacities are an uncommon finding; they are due to fibrosis or to widespread interstitial granulomas rather than alveolitis. The prognostic meaning of ground glass opacities is uncertain. Therefore, disease activity findings are mainly lymphadenopathies, nodules and consolidations. Nevertheless these findings not necessarily imply a bad prognosis, as acute sarcoidosis seems to respond well to steroid therapy, even with complete remission. It remains debated if a CT study is worthwhile in all the new cases of sarcoidosis or only in the clinically more severe ones.