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Biomedical subjects

S Marino

Publications and source records attributed to S Marino.

At least 55 records · Page 3Linked to original sources
PubMed1995

Novel metal-binding proteins by design.

We describe the successful design of a tetrahedral His3Cys Zn(II)-binding site in a small protein of known structure: the B1 domain of Streptococcal protein G. The B1 variants containing the novel metal-binding site were characterized using a combination of optical absorption, circular dichroism and NMR spectroscopies. The results indicate that the designed proteins bind Zn(II) with high affinity and tetrahedral coordination geometry, and that the overall secondary and tertiary structure of the B1 domain is maintained.

Amino Acid Sequence↗
PubMed1995

Propylthiouracil tasting: determination of underlying threshold distributions using maximum likelihood.

The ability to taste low concentrations of propylthiouracil (PROP) and related bitter compounds is heritable. The current analysis determines whether the distribution of PROP taste thresholds is consistent with an additive or a dominant mode of Mendelian transmission. To that end, the lowest concentration of PROP detectable was determined for 1015 subjects and models of bi- or tri-modal distributions of PROP taste thresholds were tested. The model with the greatest likelihood had three distributions and followed an additive model of PROP taste sensitivity if the variances associated with the distributions were assumed to be equal. However, if the taste thresholds were transformed to remove skewness, or if the variances were unequal, then three- or two-distribution models were equally likely. Resolution of the mode of inheritance for bitter taste perception awaits additional family studies and the characterization of the molecular basis of taste perception for these bitter compounds.

Adolescent↗
PubMed1995

Activation of HIV transcription by human foamy virus in transgenic mice.

BACKGROUND: Although infection by HIV-1 is the primary cause of AIDS, cofactorial agents of an infectious nature may be involved in the pathogenesis of the disease. The present work addresses the cofactorial potential of human foamy virus (HFV) in AIDS. It has been suggested that HFV seroprevalence reaches 5% in East Africa, and HFV seroprevalence in East African patients suffering from AIDS and AIDS-related complex may be as high as 20%. Although the pathogenic potential of HFV in humans has not yet been investigated in detail, HFV transgenic mice develop an encephalopathy reminiscent of some of the features of HIV-associated brain diseases. EXPERIMENTAL DESIGN: We set out to investigate the possibility that the regulatory genes of HFV may act as transcriptional cofactors of HIV. To study the effects of bel1, the transcriptional activator of HFV, on the HIV-1 LTR, we generated double transgenic mice for bel1 and for the HIV-1 LTR linked to a lacZ reporter gene. Moreover, to identify the cis-acting elements mediating bel1 action on the HIV LTR, we analyzed the consequences of deletions in the negative regulatory element or in the NF-kappa B binding sites. RESULTS: We demonstrate that bel1 is capable of activating the transcription of HIV-1 LTR in vivo. Such transactivational activity, however, was observed exclusively in a subset of hippocampal neurons, whereas cortical neurons expressing bel1 did not show transactivation. Transactivation was completely abolished by the deletion of the NF-kappa B binding sites. In contrast, deletion of the negative regulatory element region seems to enhance transactivation of bel1 on HIV-1 LTR over a prolonged period of time. CONCLUSIONS: Our study indicates that transcriptional transactivation of HIV-1 by HFV can be accomplished in vivo and is dependent on NF-kappa B binding sequences. Therefore, transcriptional transactivation is a potential mechanism of cooperation between HFV and HIV. It is conceivable that this phenomenon attains clinical significance in a situation of coinfection with both viruses.

Animals↗
PubMed1994

Tumor cell proliferation and apoptosis in medulloblastoma.

The distribution of proliferating cell nuclear antigen (PCNA)-(clone PC 10)- and Ki-67-(clone MIB-1)-positive nuclei was investigated in 60 medulloblastomas of childhood. Although the labeling index of the two markers did not coincide, both showed a wide range of parallel variations. The percentage of positive nuclei was similar in both classic and desmoplastic tumors. A variable proliferation capacity was found in the different tumor structures. Areas with neuronal and glial differentiation showed very few positive nuclei; these were very abundant in the infiltration areas, and along penetrating vessels from subarachnoidal growths. Pale islands were negative or positive only in their peripheral part. Large-cell areas were richer in positive nuclei than classic ones, accounting for their more malignant character. Hyperchromatic round nuclei, not belonging to necrotic foci and called lymphocyte-like nuclei, differently interpreted in the past, were variably found in every case. They are known, from previous experience, to stain orange with Acridine Orange fluorochroming, like single-stranded DNA. They were not easily distinguishable from mitoses and were stained by in situ end-labeling of DNA strand breaks, as demonstrated by incorporation of labeled nucleotides. They were regarded as possible apoptotic nuclei, representing either a peculiar type of cell death or the preservation of the cell deletion capacity, typical of the embryonal tissue of origin.

Adolescent↗
PubMed1994

A study of apoptosis in normal and pathologic nervous tissue after in situ end-labeling of DNA strand breaks.

Programmed cell death (PCD) via apoptosis is characterized by nuclear pyknosis and fragmentation, and biochemically by oligonucleosomal cleavage of DNA. Apoptosis occurs in the developing nervous system, whereas its role in neurodegenerative diseases is still debated. Recognition of apoptotic cells has recently been facilitated by in situ end-labeling (ISEL) techniques which identify DNA strand breaks through incorporation of labeled nucleotides. We have applied two ISEL assays to physiological and pathological conditions affecting the nervous system in which PCD is likely to occur. Terminal transferase assay was more sensitive than DNA polymerase assay and allowed the recognition of a larger number of cells than conventional histology. Apoptotic cells were readily found in the developing spinal cord and dorsal root ganglia. Medulloblastomas, gliomas, brain lymphomas and metastases showed abundant apoptotic cells either isolated or grouped in small foci. Labeling was also found in cells without a clearcut apoptotic morphology. Apoptotic cells were not found in Alzheimer's disease, amyotrophic lateral sclerosis and human and mouse prionic encephalopathies. Our results show that ISEL is a useful technique for demonstrating apoptotic cells in nervous tissue during development and in brain tumors. Lack of staining in neurodegenerative diseases suggests that other types of PCD might be involved.

Animals↗
PubMed1993

Ill-health and social predictors of psychotropic drug prescription in general practice.

Prescriptions of psychotropic drugs among 505 consecutive attenders on a single day at 32 general practices were recorded. For 404 of them the results of a screening for psychiatric morbidity conducted by means of the General Health Questionnaire (GHQ) were available. Among attenders recognised as psychiatric cases by their general practitioners the presence of concurrent somatic problems exerted a significant effect in reducing the relative odds of prescription. A very strong and significant interaction effect between male sex and high GHQ score was detected: men scoring over the threshold on the questionnaire had a risk of receiving a psychotropic drug prescription 49 times higher than the general sample. Social problems-related factors did not show significant effects when included in multivariate models comprising ill-health risk factors.

Adult↗
PubMed1990

Psychiatric morbidity in general practice in Italy. A point-prevalence survey in a defined geographical area.

Psychiatric morbidity among 505 attenders on a single day at 32 general practices in South Verona was assessed using the General Health Questionnaire (GHQ-30) and recordings of practitioners' evaluations. The usual GHQ scoring system with a cut-off point of 5/6 resulted in 52% of high-scorers while the scoring system for longstanding psychological distress conditions (C-GHQ) yielded 37% of high-scorers (cut-off point 11/12). General practitioners identified 28% of attenders as cases. One-day population based prevalence estimates for the GHQ-30 and practitioners' assessment gave values of 6.6 and 4.5 per 1000 at risk. Among several possible risk factors, only presence of previous psychiatric illness increased significantly the relative risk of being a case in terms of GHQ, C-GHQ scores and practitioners' assessments. These findings are discussed in relation to the results of other surveys in the same area and other general practice studies.

Adult↗
PubMed1990

Dose-related effect of beclomethasone dipropionate on airway responsiveness in asthma.

The effects of twice daily inhaled beclomethasone dipropionate (BDP) at two dose levels (500 and 1,000 micrograms daily) on the airway responsiveness to inhaled histamine was evaluated by a randomized, single-blind, cross-over study in 10 patients with stable asthma. The 12-week study began with a 3-week run-in period of baseline treatment, which was continued unchanged throughout the study, and the two treatment periods were separated by a 3-week placebo period. Patients attended the laboratory every 3 weeks for spirometry and histamine inhalation tests to determine the provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 s (PC20 of FEV1). There was a similar significant improvement (p less than 0.05) in mean FEV1 after both treatments. There was no significant change in PC20 after treatment with 500 micrograms daily, the geometric mean being 0.587 mg/ml after the placebo period and 0.860 mg/ml after BDP treatment. There was a significant improvement in PC20 (1.930 mg/ml) after treatment with 1,000 micrograms BDP daily in comparison with the placebo and treatment periods with 500 micrograms BDP daily (p less than 0.001). These results suggest that higher doses than usual of inhaled BDP must be used to control airway responsiveness in asthmatics.

Adult↗
PubMed1990

Effect of beclomethasone dipropionate on the bronchial responsiveness to propranolol in asthmatics.

The effect of four weeks of treatment with beclomethasone dipropionate (BDP, 500 micrograms twice daily) on the bronchial responsiveness to propranolol was examined in 16 patients with mild asthma in a placebo-controlled, double-blind crossover study. Propranolol was inhaled in doubling concentrations and the results were expressed as the cumulative dose producing a 20 percent fall in FEV1 (PC20). After four weeks of treatment with BDP, the mean FEV1 increased from 82.0 percent predicted to 88.1 percent predicted. The difference was significant (p less than 0.001). Treatment with BDP did not significantly change the responsiveness to propranolol, the geometric mean PC20 being 3.17 mg/ml before and 3.64 mg/ml after BDP treatment. The recovery of FEV1 was faster after 60 minutes of BDP treatment in comparison with placebo treatment (beyond 90 minutes). This study suggests that BDP treatment is unable to reduce bronchial responsiveness to propranolol but can accelerate the recovery of bronchoconstriction induced by propranolol in asthmatic patients.

Administration, Inhalation↗
PubMed1990

[Epidemiology of mental disorders in general practice].

A high prevalence of minor psychiatric symptoms is present in the community. When observed at the general practice level, the symptomatology has by this time usually developed to such a degree to induce help-seeking and has acquired the status of an evident clinical and health problem. Hence, general practice attenders constitute a relevant intermediate area of research for psychiatric epidemiology placed between community surveys and surveys based on contacts with specialistic services. Psychiatric morbidity has revealed itself as a major clinical problem for general practitioners, since the large majority of patients with emotional distress problems are recognized and treated in general practice services. The present paper reviews the major international studies on the topic and recent studies put forward in Italy by the Psychiatric Epidemiology Research Unit of Verona University.

Family Practice↗
PubMed1989

Microdosimetric measurements and the variance-covariance method. Some experimental experience.

Systematic and statistical uncertainties in the variance-covariance method have been investigated. Two spherical wall-less detectors have been used to determine the dose mean lineal energy (yD) in a neutron beam of 5.7 MeV produced by a Van de Graaff accelerator. It is shown that certain systematic uncertainties influenced the mean yD of the two detectors much less than yD from only one of them. A statistical uncertainty of 6% (95% confidence level) was achieved if yD was calculated from 2000 measurements. In this particular experiment insufficient shieldings of the preamplifiers positioned in the beam turned out to limit the possibility to measure below 20 nm.

Analysis of Variance↗
PubMed1989

Inv(8)(p23q22) and recombinant derivative in a Sicilian family.

A family with inv8(p23q22), in which one girl with a derivative chromosome 8 showed the characteristic phenotype, is reported. Our case differs from the 32 known families with inv8(p23q22), being the first of apparently non-Hispanic descent. The anomaly may, however, have its origins in the Spanish domination of Sicily.

Abnormalities, Multiple↗
PubMed1988

Increased responsiveness to histamine after propranolol in subjects with asthma nonresponsive to the bronchoconstrictive effect of propranolol.

Eight nonsmoking subjects with asthma, nonresponsive to the bronchoconstrictive effect of oral propranolol, were studied. The airway response to increasing concentrations of histamine aerosol was assessed by measuring FEV1. The threshold provocative dose of histamine needed to cause a 20% fall in starting FEV1 (PD20) was measured by log dose-response curve. Histamine challenge was performed in duplicate after premedication with placebo or 40 mg of propranolol on separate days. The mean starting FEV1 did not change significantly after placebo and after propranolol administration. The mean PD20 values after propranolol (0.37 mg/ml and 0.32 mg/ml, respectively, for the first and the second challenge) were significantly lower (p less than 0.01) than mean control PD20 values (1.36 mg/ml and 1.48 mg/ml, respectively, for the first and the second challenge). These results indicate that propranolol increases airway responsiveness to histamine, even in those subjects with asthma in whom propranolol has little bronchoconstrictive effect.

Adult↗
PubMed1988

Safe and cost-effective cleaning of pressure-monitoring transducers.

The CDC category I recommendation for high-level disinfection of pressure-monitoring transducers between uses imposes substantial costs. This practice has not been shown to be useful when disposable transducer domes are used. A prospective, randomized, double-blind study assessed the consequences of wiping transducers with alcohol between uses rather than sterilizing with ethylene oxide. We studied 5,197 transducer courses with disposable domes involving 2,202 patients in intensive care units during 15 months. There was no significant difference between the two treatment regimens in the risk of positive cultures of fluids from monitored lines, of cultures of cannula tips or of a positive blood culture. We conclude that under normal conditions, ie, in the absence of a cluster of transducer-related bacteremias, wiping transducers with alcohol between uses is sufficient when disposable domes are used.

Catheterization↗