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Biomedical subjects

D Caputo

Publications and source records attributed to D Caputo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Augmented type 1 cytokines and human endogenous retroviruses specific immune responses in patients with acute multiple sclerosis.

In vitro antigen- and mitogen-stimulated cytokine production were analysed in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). We also investigated whether immune responses to human endogenous retroviruses (HERV) could be detected in MS and whether these immune responses would be correlated with disease status by analysing cytokine production after stimulation of PBMC with HERV peptides. Results showed that mitogen-stimulated IL-2 and IFN-gamma was augmented and IL-10 was decreased in AMS compared to both SMS and healthy controls. Whereas the production of the metabolically active IL-12 (p70 heterodimer), was comparable in SMS, AMS and HC, production of the total IL-12 (p70 heterodimer and the p40 chain) were augmented in SMS compared to both AMS and HC. HERV-peptides IL-2 and IFN-gamma production was more frequent and more potent in AMS compared to both SMS patients and HC. HERV-specific type 2 cytokine production was more frequent and potent in SMS compared to AMS and HC. Thus a prevalent type 1 cytokine profile was seen in AMS patients, while IL-10 production predominated in SMS individuals.

Acute Disease↗
PubMed2000

Presence of autoantibodies against complement regulatory proteins in relapsing-remitting multiple sclerosis.

Complement was proposed to play an important role in the onset of Multiple Sclerosis (MS) lesions by inducing physical damage to myelin-producing cells. Every somatic cell is however endowed with a repertoire of membrane-bound molecules which normally down-regulate the complement activation cascade (Regulators of Complement Activation, RCA) and therefore protect cells from complement-dependent lysis. We show here that antibodies against two complement regulatory molecules expressed in the membrane of human cells (CD46 and CD59) are present in sera from relapsing-remitting MS patients in the acute phase, that they are directed against the active site of the RCA molecules and that they inactivate their regulatory function, thus providing a mechanism by which cells of the nervous system might be damaged in a complement-dependent fashion during the acute MS phase. Moreover, we found that most of these sera also contain antibodies reacting with an epitope of the transmembrane glycoprotein of HIV which is conserved in most retroviruses; this may support the hypothesis that self-reacting antibodies might have arisen in these patients as an immune response after retroviral infection or expression of endogenous retroviral proteins.

Acute-Phase Reaction↗
PubMed2000

Serum auto antibodies presence in multiple sclerosis patients treated with beta-interferon 1a and 1b.

To verify the possible effect of IFN-beta treatment on auto antibodies development in multiple sclerosis (MS) we studied 69 MS patients before and during the treatment with IFN-beta 1b (n=35) and IFN-beta 1a (n=20) for 27 and 12 months respectively, and, as controls, 14 untreated MS patients. The serum, collected every 3 months from all the patients, was investigated for the presence of antinuclear (ANA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-native DNA (nDNA) anti-cardiolipin (aCL), anti-parietal cells (APCA), anti-microsomal (AMC) and anti-tireoglobulin (ATG) antibodies. Among the IFN-beta 1b-treated MS patients an increase of the frequency and of the level of ANA, AMC and ATG was observed. ASMA and ANA antibodies were already present in about 45% of the MS patients before the treatment and fluctuated over the time. In one patient the treatment was interrupted after 6 months because of the occurrence of high ASMA level and of an autoimmune hepatitis. The data obtained in the smaller number of MS patients treated with IFN-beta 1a were very similar. No increase in aCL level was observed during both the IFN treatments. Our results indicate that the treatment with IFN-beta induces an increase of AMC and ATG antibodies in MS patients and confirm that, although rare, autoimmune diseases could be observed. The possible effect of these auto antibodies on the treatment efficacy and on MS clinical course need to be further investigated.

Adjuvants, Immunologic↗
PubMed2000

Endothelin and nitric oxide levels in cerebrospinal fluid of patients with multiple sclerosis.

In order to investigate the potential role of endothelins (ETs) and nitric oxide (NO) in the pathogenesis of multiple sclerosis (MS) we evaluated the levels of these vasoactive mediators in cerebrospinal fluid (CSF) of relapsing remitting MS patients and in a group of subjects with other neurological diseases (OND) and in a control group of subjects without neurological disease. Eighty patients affected from clinically diagnosed MS were selected, 44 of them were studied during an acute clinical attack and 36 in a stable phase. The OND group included 21 subjects affected by degenerative non inflammatory (n=9) and inflammatory (n=12) neurological disease while the control group included 22 subjects with cancer of the prostate (n=11) and with bladder disease (n=11). ET levels were significantly increased in CSF of relapsing remitting MS patients with an acute clinical attack in comparison with those in a stable phase, the OND group and the control group. Moreover significant differences were observed among the four groups with regard to the NO levels: MS patients in a stable and acute phase like OND group have high levels of NO compared to the control group. Since the blood-brain barrier index values did not differ significantly between the three groups, the data of this study suggest an important role for NO and ET in cerebral microcirculation in MS patients.

Acute Disease↗
PubMed2000

Molecular evidences for a role of HSV-1 in multiple sclerosis clinical acute attack.

To verify the possible role of human herpesviruses as triggering or aggravating factors in relapsing-remitting multiple sclerosis (RRMS) clinical acute attack, we studied the prevalence of some herpesviruses in the peripheral blood mononuclear cells (PBMCs) collected from 22 MS patients during an MS relapse and in a stable phase and from 18 healthy controls (HC). DNA belonging to Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), Human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and Human Herpes virus 6 (HHV-6) has been searched by specific nested polymerase chain reaction (n-PCR). EBV and HHV6 DNA has been detected with high frequency in acute and stable MS and in healthy controls without significant differences. HCMV DNA was observed both in acute and stable MS but not in HC, and, more interestingly, HSV-1 DNA was only found in 13% of acute MS, while both stable MS and healthy controls were negative. On the basis of these results we focused on HSV-1, and to confirm them and to demonstrate that HSV-1 is actively replicating in MS patients during clinical relapse, we searched both messenger RNA (mRNA) and DNA of HSV-1 in the PBMCs of 15 acute MS patients and 15 healthy controls. We found HSV-1 mRNA and DNA in a significant number of acute MS patients but not in the control group. On the whole these data indicate that HSV-1 reactivate in the peripheral blood of MS patients during clinical acute attack and probably play a role in the triggering of MS relapses.

Acute Disease↗
PubMed2000

Grading brainstem involvement in multiple sclerosis - by means of electro-oculography.

One of the most frequent disorders of the brainstem in multiple sclerosis (MS) is internuclear opthalmoplegia (INO). The aim of this study is to show how it is possible to monitor the course of MS grading INO on the basis of electro-oculographic findings. We selected 130 patients with a diagnosis of clinically defined multiple sclerosis (78 males and 52 females, mean age 43.5 years) from a population of 354 MS patients. Both saccadic eye movements and spontaneous, vestibular (VOR), visuo-vestibular (VVOR) and optokinetich nystagmus (OKN) were assessed. Slowing of the adducting eye was considered as a sign of lesion of the interocular pathways. Statistical analyses showed that the most sensitive test was VVOR, the least sensitive being randomised saccades. An impairment of random saccades was always associated with abnormal results on all other tests. It seems thus possible to grade the involvement of the medial longitudinal fasciculi (MLF) in MS from an abnormality limited to the VVOR test up to an impairment of randomised saccadic movements. Grading brainstem involvement in MS is particularly important in therapeutic trials and during rehabilitation.

Adult↗
PubMed1999

Immune responses to antigens of human endogenous retroviruses in patients with acute or stable multiple sclerosis.

A possible role for human endogenous retroviruses (HERV) in the pathogenesis of MS was investigated by analyzing HERV peptides-stimulated proliferation and cytokine production in MS patients with acute (AMS) or stable (SMS) disease. HERV peptides specific-proliferation and type 1 cytokine production by peripheral blood mononuclear cells was observed in AMS but not in SMS individuals, in whom a type 2 cytokine profile dominates. HERV peptides-stimulated immune responses were modified by changes in disease expression; mediated by CD4+ T lymphocytes; and not related to HLA class II molecules. These data suggest the possibility of a pathogenic role for HERV and HERV-specific immune responses in MS.

Acute Disease↗
PubMed1999

Validation of Italian multiple sclerosis quality of life 54 questionnaire.

OBJECTIVES: Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS: The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS: The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8. 5). Patients' participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patients v 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS: The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

Adult↗
PubMed1999

Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans.

The objective of this Phase I/II study was to assess the potential for green tea to be used as a colorectal cancer chemopreventive agent. This study measured the dose-related biological effects of administration of a single dose of green tea on the rectal mucosa of normal volunteers. Volunteers were admitted to the Robert Wood Johnson Medical School Clinical Research Center for 24 h. Baseline blood and rectal biopsy samples were obtained before the volunteers drank 0.6, 1.2, or 1.8 g of green tea solids dissolved in warm water. Blood samples were taken 2, 4, 8, and 24 h after the tea administration. Rectal biopsies were obtained at 4, 8, and 24 h. Prostaglandin E2 (PGE2) levels were analyzed by ELISA. Tea polyphenol levels in the blood, urine, and rectal tissue were measured by high-performance liquid chromatography using a Coulochem electrode array detection system. Statistical comparisons were made using ANOVA. Decreased levels of PGE2 in rectal mucosa were observed at 4 and 8 h after consumption of green tea. There was no correlation between inhibition of PGE2 and tissue or plasma levels of tea polyphenols. Ten of 14 subjects demonstrated a response to green tea, as evidenced by at least a 50% inhibition of PGE2 levels at 4 h. We conclude that green tea constituents have biological activity in inhibiting PGE2 synthesis. Given the 71% "response rate," we believe these data support the study of green tea as a colorectal chemopreventive agent in more long-term Phase II trials.

Administration, Oral↗
PubMed1998

Cytokine production and surface marker expression in acute and stable multiple sclerosis: altered IL-12 production and augmented signaling lymphocytic activation molecule (SLAM)-expressing lymphocytes in acute multiple sclerosis.

Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+ SLAM+, and CD4+ CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.

Acute Disease↗
PubMed1998

Detection of JC virus DNA in cerebrospinal fluid from multiple sclerosis patients.

JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), has been proposed as a possible aetiopathogenic factor in multiple sclerosis (MS). We performed a study to search the LT region of JCV genome by nested PCR in cerebrospinal fluid (CSF), peripheral blood mononuclear cell (PBMC) and urine samples collected from 121 MS patients, 24 patients with other neurological disorders (OND), 30 non neurological patients (NND) and in PBMCs and urine of 40 healthy subjects. JCV DNA has been found in the CSF of 11 MS patients (9%) while all the CSFs from the 24 OND and the 30 NND cases were negative. No significant differences have been observed as regard to the frequency of JCV DNA detection in PBMCs and urine between the MS patients and the control groups. Nucleotide sequences analysis of seven JCV CSF isolates showed that five strains were identical the prototypal strain, while the other two had a base mutation (T-->C) in 4286 nucleotide (nt). The finding of JCV DNA in the CSF of MS patients suggest that JCV could play a role in the triggering and/or in the maintenance of MS aetiopathogenic process, and therefore it should be taken in consideration when monitoring this disease.

Adolescent↗
PubMed1997

Human T-cell lymphotropic virus tax and Epstein-Barr virus DNA in peripheral blood of multiple sclerosis patients during acute attack.

OBJECTIVES: A study was performed to determine whether persistent or latent viruses are reactivated during the acute attack in relapsing remitting multiple sclerosis (MS). MATERIAL AND METHODS: DNA of herpes simplex virus type 1 and 2 (HSV-1 and -2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), JC virus (JCV) and HTLV-I was searched, using nested polymerase chain reaction (PCR), in peripheral blood mononuclear cells (PBMCs) collected from 14 MS patients on the first day and, twice a week, during an acute attack of the disease. RESULTS: Viral DNA was detected, in at least one PBMC sample, in all the patients. Interestingly, EBV DNA was found in 42.8% of the patients on the first day, while a sharp increase of the HTLV tax-rex DNA frequency (35.7%) was observed on the tenth day. CONCLUSIONS: In MS relapse EBV DNA detection is an early, frequent event, while the finding of tax-rex, but not of other HTLV-I genomic regions, is a secondary phenomenon, suggesting that these two factors could interact in the pathogenesis of MS relapses.

Adult↗
PubMed1995

Evidence for a missed signal to the CD8+ cells in CSF of multiple sclerosis patients.

Peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte subpopulations, defined by various T-cell specific monoclonal antibodies and flow cytometry, were analysed in 44 relapsing remitting multiple sclerosis (RRMS) patients (including 21 subjects in the acute phase and 23 in the stable phase), 40 chronic-progressive multiple sclerosis (CPMS) patients, and 24 patients with other neurological diseases (OND), in order to verify the presence of any abnormality in the lymphocyte subset pattern. A significant increase in the total number of T-lymphocytes and the CD4+ subpopulation was found in the PB of the MS patients in comparison with the OND group. Moreover, a not statistically significant increase in CD4+ cells was observed in the CSF of MS patients. A statistically significant increase was also found in the CD4+ Leu 8+ (suppressor inducer) cells in the CSF of all of the MS groups. Finally, the CD8+ (suppressor/cytotoxic) cell levels, were significantly lower in the CSF of CPMS and stable RMS patients than in the CSF of the OND patients. As a whole, our data suggest that the immunosuppressive deficit that seems to be a constant finding in MS is not due to a decrease in suppressor inducer cell levels, as previously suggested, but may be caused by a missed or altered signal from the suppressor inducer to CD8+ suppressor cells.

Adult↗
PubMed1995

HTLV tax-rex DNA and antibodies in idiopathic amyotrophic lateral sclerosis.

In an attempt to verify the possible role of retrovirus in idiopathic amyotrophic lateral sclerosis (ALS), the sera of 21 ALS patients admitted to the Neurological Unit of the Don Gnocchi Foundation in Milan, Italy, and of 9 ALS patients from Ulm University in Germany have been evaluated for the presence of antibodies to the human T-lymphotropic viruses (HTLV-I and HTLV-II). The sera of 30 healthy individuals and 20 HIV-infected but HTLV-negative subjects have been also studied as control. Moreover, the HTLV tax-rex and pol DNA sequence have been searched in the peripheral blood mononuclear cells (PBMCs) of 15 ALS patients and 15 HIV-positive HTLV-negative subjects using a nested PCR currently employed in our laboratory for the study of HTLV infections. Antibodies to one or more HTLV proteins have been found by using a Western blot (WB) kit in the sera of 10 Italian and 7 German ALS cases, while all the healthy controls were negative and only one HIV-positive subject had antibodies to HTLV gp21. HTLV tax-rex sequences have been found in the PBMCs of 6 ALS patients while all the controls were negative. All 15 ALS cases and controls were negative for HTLV pol DNA indicating that only the most conserved region of the HTLV genome could be detected. On the whole our data indicate that some ALS patients have antibodies to HTLV proteins and that the tax-rex region of the HTLV genome can be found in their PBMCs.

Adult↗
PubMed1993

MRI and cognitive patterns in relapsing-remitting multiple sclerosis.

We studied the relationships between magnetic resonance imaging (MRI) and the Luria-Nebraska Neuropsychological Battery (LNNB) in 64 patients with relapsing-remitting multiple sclerosis (MS). MRI films were scored according to arbitrary descriptive criteria designed to emphasize patterns of alterations. Five groups were created: group 1 and 2 had typical discrete white matter lesions, group 3 had confluent lesions, group 4 had large discrete lesions and group 5 had only few small lesions. In addition, groups 2 and 3 had evidence of parenchymal atrophy. Groups 2 and 3 were the most impaired on the LNNB, but none of these patients was actually demented. Groups 1 and 5 were globally intact in spite of very different mean age and MRI pattern. Group 4 was composed of younger subjects with a shorter disease duration; they showed mild loss of attentive and abstracting abilities. We suggest that since their MRI was showing greater signs of local biological activity their mental deficits may be a transitory condition capable of two distinct outcomes: a favorable one as in groups 1 and 5, and a slowly progressive one associated with loss of brain tissue as in groups 2 and 3.

Adolescent↗
PubMed1993

Enzymes of lysosomal origin in the cerebrospinal fluid and plasma of patients with multiple sclerosis.

Several lysosomal enzymes were determined in 47 and 62 samples of CSF and plasma, respectively, obtained from MS patients. CSF levels of most enzymes considered were significantly lower in patients when compared to those of the controls, whereas the plasma levels vary little and appeared to be influenced by the course of the disease. The most interesting result is the one concerning the beta-D-glucuronidase in the plasma: in relapsing-remitting patients in the still untreated acute phase, the levels remain noticeably diminished in comparison to controls. The data suggest the potential of using this enzyme to monitor the progression of the disease.

Adolescent↗
PubMed1990

HTLVI antibodies in multiple sclerosis and other neurological diseases.

The sera and the CSFs from 157 Multiple Sclerosis (MS) patients and 43 other neurological diseases (OND) cases have been evaluated for the presence of HTLVI antibodies. A commercial passive agglutination assay (PPA), an indirect fluorescence assay (IFA), and a Western Immunoblotting (WIB) performed in our laboratories have been employed. No OND samples showed HTLVI antibodies, while 14 sera and 1 CSF from MS patients resulted positive by PPA and 4 sera were positive with the IFA. When tested with WIB 6 MS sera showed a reactivity against one or more HTLVI proteins. Our results lead us to affirm that in a small number of MS patients, when sensitive tests are employed, it is possible to observe an antibody response toward proteins that share one or more epitope with HTLVI antigens.

HTLV-I Antibodies↗