The bovine cocaine and amphetamine-regulated transcript locus: gene characterization and SNP discovery.
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Animals↗
Biomedical subjects
E Valle
Publications and source records attributed to E Valle.
Genomic localization and SNP discovery in the bovine melanocortin receptor 4 gene (MC4R).
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Animals↗
Production and characterization of monoclonal antibodies to E1 Tor toxin co-regulated pilus of Vibrio cholerae.
Murine monoclonal antibodies (MAbs) against Vibrio cholerae toxin co-regulated pilus (TCP) were generated using conventional hybridoma procedures. Four hybridomas were obtained and two characterized. Hybridomas 10E10E1 and 4D6F9 secreted antibodies of the IgG2a and IgG1 isotypes, respectively, that reacted with a 24-kDa antigen corresponding to the product of the El Tor tcpA gene fused to a six Histidine tail. Additionally, MAbs produced by 4D6F9 selectively recognized the major pilin subunit (TcpA) of El Tor and O139 vibrios in western immunoblot, while MAbs from 10E10E1 also cross-reacted with classical TcpA. Furthermore, vibrios expressing TCP on their surface selectively inhibited binding of the antibodies secreted by both hybridomas to TcpA-coated microtiter plates. Thus, the MAbs reported in this work detected the structural subunit of the pilus either denatured or assembled on the bacterial surface.
Animals↗
Differential interleukin-8 response of intestinal epithelial cell line to reactogenic and nonreactogenic candidate vaccine strains of Vibrio cholerae.
In this study, we analyzed whether attachment of Vibrio cholerae vaccine strains to human intestinal epithelial cells can induce an interleukin-8 (IL-8) response. The IL-8 transcripts were detected by PCR amplification of reverse-transcribed mRNA, and the gene product secretion was measured by an enzyme-linked immunosorbent assay. Infection of monolayers of the undifferentiated HT29-18N2 cell line with reactogenic (JBK70 and 81) and nonreactogenic (CVD103HgR and 638) vaccine strains of V. cholerae resulted in markedly higher IL-8 expression by epithelial cells exposed to reactogenic strains than by cells exposed to the nonreactogenic strains. Additionally, epithelial cells produced IL-8 transcripts following stimulation with cholera vaccine strains in a concentration-dependent manner. These results represent a new insight into the inflammatory component of reactogenicity and could be used as a predictive marker of vaccine reactogenicity prior to human testing.
Bacterial Adhesion↗
Infliximab.
Infliximab (Remicade, Centocor, Inc.) is an intravenously administered monoclonal antibody to TNF proven effective in the treatment of moderate to severe Crohn's disease (CD). Its introduction in October 1998 was heralded by some as the most important addition to therapy for this condition in 50 years. Since then, additional indications have been added as efficacy has been proven in fistulising CD and in rheumatoid arthritis. Even though the costs associated with a single dose are several thousand US dollars, more than 150,000 patients have received infusions since its approval.
Antibodies, Monoclonal↗
Physicians' attitudes to and problems with truth-telling to cancer patients.
Disclosure of a diagnosis of cancer to patients is a major problem among physicians in Italy. The aim of the study was to assess physicians' attitudes to and opinions about disclosure. A convenience sample of 675 physicians in Udine (North Italy) completed a ten-item questionnaire. About 45% indicated that, in principle, patients should always be informed of the diagnosis, but only 25% reported that they always disclosed the diagnosis in practice. Physicians with a surgical specialization employed in general hospitals endorsed disclosure of the diagnosis more frequently than GPs and older physicians. One third of the responding physicians persist in the belief that the patients never want to know the truth. Hospital doctors considered the hospital, rather than the patient's home, was the most appropriate place to inform the patients. The opposite result was found among GPs. Almost all the physicians endorsed the involvement of family members when disclosing the diagnosis, but, at the same time they also indicated that families usually prefer their ill relative not to be informed. Ninety-five per cent of physicians believed that the GP should always be involved in the processes of diagnosis and communication, and 48% indicated that the GP should communicate the diagnosis to the patient (as opposed to the physician who made the diagnosis). Having guidelines for breaking bad news to patients was indicated as an important need by 86% of the responding physicians. Despite changes in medical education, improvement of communication skills in dealing with cancer patients and their families represents an important need in healthcare settings.
Adult↗
Construction and characterization of a nonproliferative El Tor cholera vaccine candidate derived from strain 638.
In recent clinical assays, our cholera vaccine candidate strain, Vibrio cholerae 638 El Tor Ogawa, was well tolerated and immunogenic in Cuban volunteers. In this work we describe the construction of 638T, a thymidine auxotrophic version of improved environmental biosafety. In so doing, the thyA gene from V. cholerae was cloned, sequenced, mutated in vitro, and used to replace the wild-type allele. Except for its dependence on thymidine for growth in minimal medium, 638T is essentially indistinguishable from 638 in the rate of growth and morphology in complete medium. The two strains showed equivalent phenotypes with regard to motility, expression of the celA marker, colonization capacity in the infant mouse cholera model, and immunogenicity in the adult rabbit cholera model. However, the ability of this new strain to survive environmental starvation was limited with respect to that of 638. Taken together, these results suggest that this live, attenuated, but nonproliferative strain is a new, promising cholera vaccine candidate.
Amino Acid Sequence↗
Effect of islet transplantation on neuroelectrophysiological abnormalities in diabetic inbred Lewis rats: comparison of primary versus secondary prevention.
BACKGROUND: Neuroelectrophysiological abnormalities in diabetes indicate nervous function failure. Restoration of euglycemia by islet transplantation may prevent or reverse these abnormalities. METHODS: Pancreatic islets were transplanted in inbred Lewis rats after 15 days (Ta12, primary prevention) or 8 months (Tb12, secondary prevention) from streptozotocin-induced diabetes. Transplanted and control (normal and diabetic) rats were followed for a total period of 12 months. Metabolic parameters, somato-sensory, brain-stem auditory, and visual evoked potentials were determined at the beginning and at the end of the study and before transplantation for secondary prevention. RESULTS: The metabolic parameters in transplanted animals were similar to those of normal animals. Ta12 and normal group somato-sensory conduction velocities did not vary and were always significantly higher than those of diabetic animals. By contrast, Tb12 group conduction velocities showed only a partial improvement, values lying between those of diabetic and normal rats. Brain-stem auditory (waves I, II, and III) latencies in Ta12 group were similar to those of normal rats and significantly lower than those of diabetic animals (wave I: P<0.01; waves II and III: P<0.05). Tb12 group wave I and II latency values remained altered (P<0.005 and P<0.01 versus normal values respectively). Visual evoked potentials-P1 wave latencies in transplanted rats were always higher than those of normal and diabetic animals. CONCLUSIONS: After primary prevention, central and peripheral neurological alterations were abolished. After secondary prevention, transplantation beneficial effects were partial, occurring mainly at peripheral level. These results highlight the importance of early transplantation to prevent hyperglycemia-dependent neuroelectrophysiological alterations.
Animals↗
Autonomic involvement in multiple sclerosis: a pupillometric study.
To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.
Adaptation, Ocular↗
Bactericidal effect of ADP and acetic acid on Bacillus subtilis.
Bacillus subtilis is a ubiquitous soil bacterium used for measuring the beta-lysin activity and in other bioassays. We observed a complete bactericidal effect of ADP on B. subtilis at concentrations of 50-100 microM at pH values <5.5, which disappeared at pH values above 6. The effect was also found for acetic acid at concentrations >17.4 microM and similar pH values. ATP, adenosine, and HCl were not bactericidal. We used BCECF-AM, a pH-sensitive probe, and found that the killing of B. subtilis was due to a change in the intracellular pH caused by the passage across the cell membrane of these weak organic acids when incubated with B. subtilis at pH values near the pK. More experiments are needed to determine the biological meaning of these in vitro findings.
Acetic Acid↗
Effects of spontaneous chronic hypoglycemia on central and peripheral nervous system in insulinoma patients before and after surgery: a neurophysiological follow-up.
To investigate the effects of spontaneous chronic hypoglycemia on the peripheral and central nervous system, a multimodal neurophysiological evaluation [median somatosensory (mSEP), brain stem auditory (BAEP), and visual (VEP) evoked potentials recordings] was performed in seven insulinoma patients before and 3 and 6 months after surgical removal of tumor. Before surgery, mSEP findings showed abnormal reduction in peripheral wrist-Erb conduction velocity in three patients as well as a pathological increase in Erb-N13, N13-N20, and Erb-N20 conduction times in five cases. BAEP and VEP recordings gave pathological results in two patients. Moreover, during hypoglycemia, the III-V and I-V interpeak latencies of BAEPs were significantly prolonged (P < 0.01 and P < 0.005, respectively) compared to recordings in euglycemia. After 6 months, a mSEP recovery, even if partial was noted in four patients, BAEPs were normalized in one case, and VEPs were unmodified. Compared to presurgery data, these recordings showed a significant (P < 0.05), but incomplete, shortening of BAEPs (III-V and I-V interpeak latencies) and mSEPs (Erb-N13 and Erb-N20 conduction times). Our findings demonstrate that multiple and selective neurophysiological abnormalities are present in insulinoma patients, confirm that hypoglycemia impairs suddenly brain stem function, and show that after tumor removal, long recovery times for improvement of some neurophysiological anomalies are requested.
Adolescent↗
[The contribution of conventional EMG to the diagnosis of amyotrophic lateral sclerosis with bulbar symptoms].
INTRODUCTION: We presented here the results of quantitative electromyographic (EMG) study from 61 patients affected by Amyotrophic Lateral Sclerosis (ALS) with bulbar symptomatology at the time of study. MATERIAL AND METHODS: Patients were divided into two groups depending on whether the illness started with bulbar manifestations alone or with predominant neuromuscular weakness. RESULTS: Electromyography was performed on the abductor pollicis brevis, deltoideus or biceps brachii and tibialis anterior muscles (target muscles). In the first study the EMG was abnormal in more than 90% of the patients regardless to the duration of the illness and muscular weakness distribution. In the follow-up study the EMG was abnormal in all the patients lacking significant differences between the two groups. CONCLUSIONS: Quantitative EMG appeared as a very useful tool for the early diagnosis of ALS with bulbar manifestations. We found a correlation between the alterations of the different EMG parameters with the natural evolution of the illness.
Aged↗
Pupillometric evaluation and analysis of light reflex in healthy subjects as a tool to study autonomic nervous system changes with aging.
To assess the relationships between aging and autonomic control of pupillary functions, TV-pupillometry and light reflex evaluation were performed in 52 healthy volunteers in the age range 15-75 years, grouped into four age classes (group 1: 15-29 years, Group 2: 30-44 years, Group 3: 45-59 years, Group 4: 60-75 years). Baseline light pupil diameter was found to be age-dependent, together with light reflex contraction velocity, which presented a linear correlation with age. Light reflex amplitude and half-redilatation velocity were reduced in older subjects, but presented only a weak linear correlation with age, while latency, contraction time and half-redilatation time percent of secondary dilatation and redilatation at 5 seconds did not show significant changes with age. These results confirm that there are important age-dependent changes in the mechanisms involved in pupillary autonomic functions, regarding both sympathetic and parasympathetic components. These changes appear to be easily detectable by making use of a sensitive and non-invasive technique such as TV-pupillometry.
Adolescent↗
Peripheral, but not central, nervous system abnormalities are reversed by pancreatic islet transplantation in diabetic Lewis rats.
Neuroelectrophysiological recordings represent a non-invasive and reproducible method of detecting central and peripheral nervous system alterations in diabetes mellitus. In order to evaluate whether the normalization of metabolic control obtained by pancreatic islet transplantation could reverse diabetic neuroelectrophysiological alterations, or prevent further deterioration, we used an experimental model in which pancreatic islets (n = 1200) were injected into the portal vein of inbred Lewis rats (used as islet donors as well as recipients). Islets were injected 4 months after diabetes induction, since previous work had shown functional but not morphological damage at the nervous tissue level at this stage of the disease. Visual (V), brainstem auditory (BA) and somatosensory (S) evoked potentials (EPs) were measured in streptozotocin-induced, islet-recipient diabetic rats (n = 7), streptozotocin-induced diabetic rats (n = 16) and non-diabetic control rats (n = 12). Metabolic parameters and electrophysiological recordings were evaluated before diabetes induction, before transplantation and 4 months later. After transplantation, glycaemic levels returned to normal values within 1 week and remained so until the end of the study, as confirmed by a normal oral glucose tolerance test and by an increase in body weight. Electrophysiological recordings were altered in diabetic animals before transplantation. Four months after transplantation EP recordings improved, with a detectable gradient from the peripheral to the central structures. SEPs were significantly improved in the peripheral tarsus-L6 tract and the L6-cortex tract (P < 0.005 and P < 0.01 versus diabetic rats) and were ameliorated without achieving statistical significance in the central L6-cortex tract. BAEP latency values tended to improve in transplanted rats, but the differences versus non-transplanted diabetic animals failed to reach significance. VEP values remained clearly pathological and even deteriorated after transplantation. These results show that normalization of metabolic control by pancreatic islet transplantation can reverse some of the already established neuroelectrophysiological alterations at the peripheral nervous system level, but does not affect other alterations at the central nervous system level.
Animals↗
Treatment with cyclosporine A promotes axonal regeneration in rats submitted to transverse section of the spinal cord--II--Recovery of function.
Previous reports have suggested a correlation between autoimmunity and abortive axonal regeneration in mammalian CNS. In this study we investigated the effects of immunosuppressive treatment with Cyclosporine A (CyA) (2.5-5 mg/kg/day) on axonal regeneration after complete spinal transection in rats. Partial recovery of function was observed 30 days after surgery in rats treated with CyA, with the presence of incomplete spontaneous locomotion and a positive contact placing reaction. Restoration of somatosensory evoked potentials and positive retrograde fluorescent tracing were also observed. CyA reduced the autoimmune reaction which targeted components of the axons. These results provide further evidence of the role played by autoimmunity in blocking regeneration of fibre tracts in mammalian CNS.
Animals↗
Electrophysiological alterations of the central nervous system in diabetes mellitus.
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Animals↗
Role of advanced glycation end-products (AGE) in late diabetic complications.
To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.
Animals↗
Crural amyotrophy associated with a parietal lesion: a case report.
The authors have observed a 33-year-old woman with a 3-year history of a clinical syndrome characterised by atrophy of the musculature of the left foot and leg with impaired motor function, associated with a paracentral cortical oligodendroglioma located in the right parietal region. Clinical, neuroradiological (MRI), electrophysiological (electromyography: EMG; motor evoked potential: MEP; median and tibial somatosensory evoked potential: m-SEP and t-SEP), and neuropsychological studies were performed every year for three years. Neurological examination showed an abnormal gait along with foot drop, pes cavus and pyramidal involvement. MEP and t-SEP recordings were abnormal on the left side, while EMG and neuropsychological tests gave normal results, which were unmodified over time. Our observations suggest that the crural amyotrophy observed in this case may be defined as of "parietal" or "central" origin, a clinical feature which more frequently affects the hand. A review of the literature is presented.
Adult↗