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Biomedical subjects

A Cattaneo

Publications and source records attributed to A Cattaneo.

At least 91 records · Page 5Linked to original sources

A critical period in the sensitivity of basal forebrain cholinergic neurones to NGF deprivation.

Cholinergic neurones of basal forebrain (BF) express receptors for nerve growth factor (NGF) and are sensitive to NGF. In many CNS structures, including the BF region, the expression of NGF and its receptors is developmentally regulated. To test whether BF neurones depend on NGF during restricted time windows of postnatal development, we antagonized endogenous NGF by implanting, in the lateral ventricle of the rat, hybridoma cells producing blocking antibodies specific for NGF. Implants were performed at postnatal day 2 (P2), P8 and P15. BF cholinergic neurones were drastically reduced in number only when endogenous NGF was antagonized during the first postnatal week. We conclude that BF cholinergic neurones are sensitive to NGF deprivation only during early postnatal development.

Animals↗

Inhibition of murine leukaemia virus retrotranscription by the intracellular expression of a phage-derived anti-reverse transcriptase antibody fragment.

The intracellular targeting of recombinant antibodies is an experimental strategy to interfere with the function of selected molecules that is being utilized in a variety of different systems for research and medical applications. Since recombinant antibodies are increasingly being derived from phage display libraries, we have exploited phage technology to isolate, from a large combinatorial library, human antibody fragments directed against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). We describe in this paper the in vitro and in vivo properties of a neutralizing anti-RT antibody fragment. We demonstrate that the heavy chain domain (VH-CH1) of the phage-derived antibody is able to inhibit the retroviral enzyme, in that it neutralizes the RNA-dependent DNA polymerase activity of HIV-1 RT. The VH-CH1 antibody fragment also neutralizes the activity of RT of drug-resistant HIV-1 mutants as well as that of murine retrovirus RT. To confirm the broad reactivity of the synthetic antibody fragment, we have assessed the ability of the intracellularly expressed VH-CH1 protein to interfere with murine retroviral infection. To this end, we developed an in vivo selection procedure based on the antibody-mediated resistance to a cytotoxic retrovirus and used this selection procedure to rescue, from a heterogeneous population, cells expressing the VH-CH1 antibody fragment. We finally demonstrate that the intracellular expression of the recombinant heavy chain antibody fragment leads to an efficient inhibition of viral retrotranscription by murine-based retrovirus.

3T3 Cells↗

Fibrogenic cytokines in vulvar lichen sclerosus. An immunohistochemical study.

OBJECTIVE: To evaluate the expression of fibrogenic cytokines in lichen sclerosus (LS) infiltrate as compared with lichen planus (LP) infiltrate. STUDY DESIGN: Eight cases of vulvar LS (early stage, n = 3; well developed or old, n = 5) and 4 of vulvar LP were studied. Monoclonal antibodies directed against some of the major fibrogenic cytokines (IL-4, TGF-beta, IL-6) and against IFN-gamma, which inhibits collagen synthesis, were used per the alkaline phosphatase/anti-alkaline phosphatase technique on frozen sections. RESULTS: Staining for IL-4 revealed higher expression of fibrogenic cytokines (more than 50% infiltrating cells) in the LS infiltrate, mainly in early lesions, than in LP. Conversely, staining for IFN-gamma in LS was poor (less than 10% infiltrating cells), while strong positivity (more than 60% infiltrating cells) was found in LP. Staining for TGF-beta, a mediator of fibrosis in scleroderma, was similar in both LS and LP dermis. CONCLUSION: This study showed the immunohistochemical expression of fibrogenic cytokines in vulvar LS, with a different pattern as compared to that of LP. It is conceivable that dermal infiltrating cells actively participate, via cytokine production, in the pathogenesis of fibrosis in LS.

Adult↗

Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Acyclovir↗

The performance of SAPS II in a cohort of patients admitted to 99 Italian ICUs: results from GiViTI. Gruppo Italiano per la Valutazione degli interventi in Terapia Intensiva.

OBJECTIVE: To assess the validity of SAPS II (new Simplified Acute Physiology Score) in a cohort of patients admitted to a large sample of Italian intensive care units (ICU). DESIGN AND SETTING: The ability of the SAPS II scoring system to predict the probability of hospital mortality was assessed with calibration and discrimination measures obtained using published coefficients. A new logistic regression equation was then developed and further formal calibration and discrimination measures were estimated for the customized model. PATIENTS: From the 2202 consecutive patients recruited during a 1-month period in 99 ICUs, a total of 1393 patients were included in this validation study. RESULTS: When the parameters based on the standard model were applied, the expected probability of mortality did not fit those actually observed in the cohort (p < 0.001), although it showed satisfactory discrimination (area under the receiver operating characteristic curve = 0.80). Such lack of fit yields an overall under prediction of mortality (observed/expected ratio = 1.14) that reflects a uniform pattern across a preselected set of subgroups. Customization allowed new mortality estimates to be calculated, with satisfactory calibration (p = 0.82) and a more uniform pattern across subgroups. CONCLUSIONS: SAPS II maintained its validity in an independent sample of patients recruited in a large network of Italian ICUs only after appropriate adaptation (first-level customization). Whether the determinants of this relatively poor performance are related to differences in unmeasured case-mix, methods of application, or quality of care delivered is a matter for discussion that cannot be solved with the data presently available. However, these findings suggest that caution is warranted before implementing the standard SAPS II scoring system parameters outside formal research projects.

APACHE↗

Dexamethasone adjunctive therapy for bacterial meningitis in children: a retrospective study in Brazil.

The clinical records of 87 children with bacterial meningitis treated with antibiotics (group 1) and of 92 treated with antibiotics plus dexamethasone (group 2), admitted to the Instituto Materno Infantil de Pernambuco, Recife, Brazil over 2 consecutive years (1991 and 1992), were analysed. There were no significant differences between treatment groups regarding characteristics on admission except that group 1 were younger. The overall case fatality rate was 19%, with 14% in group 2 and 24% in group 1 (p = 0.09). Rate of discharge without sequelae was 70% in the steroid-treated children and 56% in children treated with antibiotics alone (p = 0.07). Among children aged 6-59 months, those treated with dexamethasone compared with those treated with antibiotics alone had a better case fatality rate (11% vs 25%; p = 0.05) and a better rate of discharge without sequelae (73% vs 52%; p = 0.02). Among the cases with a CSF culture positive for Haemophilus influenzae, 77% were discharged without sequelae in group 2 compared with 51% in group 1 (p = 0.03). The addition of dexamethasone to standard antibiotic treatment improves the outcome of children between 6 and 59 months of age admitted to hospital with a diagnosis of bacterial meningitis.

Adolescent↗

Human recombinant antibody fragments neutralizing human immunodeficiency virus type 1 reverse transcriptase provide an experimental basis for the structural classification of the DNA polymerase family.

We describe in this paper the binding and biochemical properties of two human antibody fragments directed against the human immunodeficiency virus type 1 reverse transcriptase (RT). These fragments were isolated from a synthetic combinatorial library of human Fab antibody fragments displayed on the surface of filamentous phage. The antibody fragments were selected by using recombinant heterodimeric human immunodeficiency virus type 1 RT purified from insect cells as a solid-phase selector. This procedure led to the isolation of two antibody fragments that completely neutralize the RNA-dependent DNA polymerase activity of RT at nanomolar concentrations. Both antibody fragments bind only to the enzymatically active form of the RT. The inhibitory activity of the anti-RT antibody fragments is competitive with respect to the template primer. The antibody fragments also neutralize the activities of RTs from avian and murine retroviruses and of DNA polymerases of prokaryotic origin as well as human DNA polymerase alpha. Thus, the antibody fragments selected and characterized in this study appear to recognize a structural fold that is common to the different DNA polymerases and necessary for their activity. The results provide an immunological experimental basis for a purely structural and evolutionary classification of the polymerase family.

Animals↗

Testosterone maintenance therapy. Effects on vulvar lichen sclerosus treated with clobetasol propionate.

OBJECTIVE: To evaluate the possible effects of topical testosterone as maintenance therapy after clobetasol propionate treatment. STUDY DESIGN: Thirty-two patients with biopsy-proven vulvar lichen sclerosus (LS), after 24 weeks of treatment with 0.05% clobetasol propionate cream, were randomly distributed into two groups of 16 each and treated for a further length of time (24 weeks) with testosterone 2% ointment or a cream-based preparation (placebo). The patients were examined before and after treatment for symptoms, gross aspects and histologic features. RESULTS: With clobetasol propionate all patients had a marked improvement (P < .001) in both clinical and histologic parameters. After clobetasol propionate therapy, the 16 testosterone-treated patients had significant worsening of their symptoms (P < .05%) and no evident changes in gross aspects (P = NS). The placebo-treated group had good symptomatic control of their disease, with no significant changes in symptoms or gross aspects (P = NS). CONCLUSION: After the good results obtained with clobetasol propionate, treatment with testosterone appeared to have a negative effect, while a regularly provided emollient cream was useful in symptom control.

Administration, Cutaneous↗

[Evaluation of activity in intensive care. A comparison of administrative and epidemiologic data].

This paper reports on results of a formal comparison of data excerpted from 3 different data sources regarding patients cared for in Italian Intensive Care Units (ICU) in 1992. The analysis was carried out in order to assess whether the administrative data routinely collected for reimbursement and policy issues are valid when compared with data from epidemiologic studies. First, using data from the Central Service for Health Planning (SCPS) a general description of the whole national scenario is shown. All the Italian data from 265 Italian hospitals having at least one ICU were analyzed. In these hospitals there were 2,357 ICU beds (4.3 beds/1000 inhabitants, with large regional variability). About 100,000 cases were identified (1% of all the hospital admissions received ICU care at some moment during the stay), with an overall hospital mortality rate of 17%. This estimate was largely different from those obtained from GiViTI data base (5100 patients from a national sample of 114 ICUs), where mortality rates were always higher (25 and 30%, for ICU and hospital mortality). Second, a more detailed analyses and comparison was carried out in the subsample of cases admitted in the Hospitals of the Regione Lombardia. In this case, beside the data from SCPS (No = 20580) and from GiViTI (No = 1121), the Regional data-base formed by all the discharge from 41 hospitals having at least one ICU were available (NO = 16674), allowing a formal comparison between estimates obtained from 3 different sources. In this sub-sample, although administrative data showed a good capability and satisfactory accuracy to describe the volume and socio-demographic and clinical characteristics of the cases when compared with GiViTI estimates, still a systematic underestimate of the overall ICU and hospital mortality was present. Moreover, an unexpected high rate of cases were apparently discharged alive from ICU (16.5 versus 32.6% in GiViTI). Tentative explanations and implications of these phenomena are discussed in the text. Finally, in the Lombardia sub-sample a formal description of the case-mix using the Diagnosis Related Group (DRG) system was carried out in order to identify strengths and limitations of this approach when adopted in the ICU setting. Overall, when data are analyzed according to the kind of Major Diagnostic Category (MDC), 75% of all cases were concentrated in 5 alone, with very peculiar concentration in some specific categories. For example, 45% of all the hospital admissions related to the multiple trauma were actually admitted in the ICU setting. At DRG level, fifty of the 493 DRGs available explained 65% of all the cases, showing an unexpected capability of this system to detect the ICU case-mix. The most represented surgical DRG was the number 107 (Coronary Arterial Bypass Graft, without catheterization) and the corresponding medical was the 28 (Cerebro Vascular Accident, excluding TIA).

Adolescent↗

[Principles of the clinical evaluation of the vulvar region].

The clinical examination of the vulva, using an articulated method, should form part of the routine gynecological examination thus enabling both the correct diagnosis and treatment of numerous alterations and the prevention and early diagnosis of VIN and invasive neoplasias. A correct evaluation should include basic anamnestic data, a list of symptoms localised in the vulva region, a careful inspection and palpation. The successive aim is to identify the main clinical aspects of the lesion which can be summarized as changes of colour, presence of swellings on surface and loss of substance. The critical evaluation of lesions should allow critical evaluation of lesions should allow the gynecologist to formulate a diagnosis to propose to the pathologist. In this way the collaboration between clinician and pathologist can contribute to progress in the diagnosis and treatment of vulvar diseases.

Diagnosis, Differential↗

Subcellular localisation of neurotrophins and neurotrophin receptors: implications for synaptic plasticity.

A growing body of recent evidence indicate that neurotrophins can act as mediators of neuronal plasticity. In the context of a more detailed, comprehensive understanding of the function of neurotrophins it is essential to characterize where neurotrophins are synthesised and stored and from where they are released. Here we present evidence that the mRNAs for NGF, trkB and BDNF but not trkA are localised in the dendrites of rat neurons, thus implying that neurotrophins and their receptors can be synthesised at locations close to their sites of function, with particular regard to the dendritic synapses. The significance of this finding and its possible implications for synaptic plasticity are discussed within the theoretical framework of the synapse-specific control of individual synapses of a given neuron.

Animals↗

Quick purification of recombinant human truncated tau proteins for immunoanalysis.

A simple and rapid purification method is described which exploits the heat stability of human tau (tau) protein to prepare truncated forms of this protein derived from bacteria. Bacterial cells expressing tau fragments were pelleted, resuspended in phosphate buffered saline and boiled for 5 min. After centrifugation the supernatant containing thermostable tau was filtered (0.45 microns) and used for immunoanalysis with monoclonal antibodies. The purified tau fragments exhibited identical antigenic properties as fragments isolated by a conventional procedure, based on ion exchange chromatography on phosphocellulose. In contrast to the conventional approach, our method is less complicated, cheaper and significantly reduces the time required for isolation of the recombinant tau fragments.

Antibodies, Monoclonal↗

Neurofilament-negative neurones exhibit HVA Ca2+ currents with faster inactivation kinetics.

The whole cell configuration of the patch clamp technique was used to study the biophysical and pharmacological properties of voltage activated Ca2+ channel currents on hippocampal neurones cultured in the presence or absence of foetal calf serum. In the presence of serum cells were intensively immunostained with neurofilament (NF) antibodies. In the absence of serum, cells were non-immunoreactive; they were identified as neurones by their ability to generate action potentials. NF negative cells still expressed both high (HVA) and low (LVA) voltage activated Ca2+ channels. However, in comparison to NF positive neurones, HVA Ca2+ currents present in NF negative neurones had a faster inactivation kinetics.

Action Potentials↗

Evaluation and retraining of adults' cognitive impairment: which role for virtual reality technology?

Immersive virtual reality (IVR) is a technology already developed to assist cognitive psychologists and therapists in their clinical work with brain-damaged patients. The rationale, the software and the hardware of the first application (ARCANA 1) based on affordable technology are discussed here, in order to provide a concrete example of what the authors think may be the role of IVR as a clinical tool. Although prospects are exciting, extensive research is needed to validate this new approach and reveal its limitations and advantages.

Adult↗

Epiphyte size and taxonomy as biological indicators of ecological and toxicological factors in Lake Saint-François (Québec).

To assess the potential of the epiphyton community for monitoring spatial and temporal variations in the environmental quality of freshwater ecosystems, this paper describes the response of epiphytons to ecological and toxicological factors in Lake Saint-François, a fluvial lake of the St. Lawrence River (Québec). First, community descriptions and biotic indices based on size structure and on taxonomic composition were compared to test if size could usefully describe epiphyton response to environmental factors. Secondly, the relative contribution of ecological and toxicological variables in explaining the variation observed in epiphyton was quantified. A size-based approach classified the sites similarly to taxonomic analysis, but a larger portion of variance in size could be explained indicating a stronger relationship with environmental factors. Among both taxonomy and size-based biotic indices, the slope of the normalized size spectra performed best in terms of total explained variance. There were strong interactions between toxicological and ecological variables. These interactions should be considered in the planning and interpretation of biomonitoring studies. In such surveys, samples should be collected at sites with similar ecological characteristics: for example, the same macrophyte type and sediment texture. Interpretation of the data should consider the possible covariance of toxicological and ecological variables.

Journal Article↗

Neuroantibodies: ectopic expression of a recombinant anti-substance P antibody in the central nervous system of transgenic mice.

Recombinant antibodies are efficiently secreted by cells of the nervous system. Thus, their local expression in the CNS of transgenic mice could be used to perturb the function of the corresponding antigen. As a first application of this approach, we have generated transgenic mice that express antibodies against the neuropeptide substance P, under the transcriptional control of the promoter of the neuronal gene vgf. The transgenic antibodies are expressed in a tissue-specific and developmentally regulated manner and are effective in competing with the endogenous substance P, as demonstrated by a marked inhibition of neurogenic inflammation and by motor deficits. This phenotypic knockout approach may provide a complementary alternative to gene knockout by homologous recombination.

Animals↗