Biomedical subjects
Publications and source records attributed to L Bracco.
This paper describes a protocol for identifying patients suspected of having Alzheimer's disease (AD) which was used in a long-term multicenter study in Italy. It relies on a progressive elimination procedure to arrive at a clinical diagnosis of 'very probable AD', with a sensitivity of 0.96 in terms of 2 years follow-up data.
An increasing number of eukaryotic transcription factors interacting specifically with DNA comprise a dimerization motif called the "leucine zipper". These leucine zipper proteins form homodimers and/or heterodimers with another protein containing a leucine zipper motif. The leucine zipper of the oncoprotein Jun is particular in that Jun may form homodimers as well as heterodimers with the oncoprotein Fos, which are however more stable than the Jun-Jun homodimers. Leucine zipper dimerization is thought to occur through a coiled-coil arrangement of parallel alpha-helices, but the rules governing the specificity of homo- and/or heterodimerization are still largely unknown. To address this question in the case of the Jun leucine zipper, we constructed a fusion protein containing the amino-terminal DNA binding domain of the LexA repressor from Escherichia coli fused to the Jun leucine zipper. This hybrid protein (LexA-JunZip) is stable in E. coli and confers much tighter repression in vivo than the DNA binding domain of LexA alone. DNA binding competition experiments with synthetic Jun and Fos leucine zipper peptides in vitro showed that the leucine zipper mediated dimerization of LexA-JunZip is essential for DNA binding of the fusion protein. The purified LexA-JunZip protein dimerizes in vitro with a dimerization constant of 2 x 10(7) M-1 at 5 degrees C. Dimerization is very sensitive to temperature, since the dimerization constant drops at 20 degrees C to 2 x 10(6) M-1 and at 30 degrees C to only 3 x 10(5) M-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Explore the source record for details and available documents.
The aim of genomic pharmacology is to discover substances able to influence the expression of specific genes. These substances could be used in many pathologies in which the expression of specific genes is abnormal and in the control of viral infection. The potential targets of genomic pharmacology may be classified in two groups: first, the proteins regulating genetic expression, and, second, the nucleic acids which carry the genetic information. The preliminary results obtained with antidirectional nucleic acids are presented and discussed.
For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress.
In prosthetics, various options are available to the orthodontist for repairing dental arches. The basic choice is between full crowns and partial crowns. Full crowns are primarily indicated for aesthetic reasons, in order to correct tooth axes and in cases of recurrent caries. Partial crowns in precious alloys are indicated when the need is not essentially aesthetic. They continue today to offer advantages in restoring posterior teeth. Because of their supragingival limits, they alleviate periodontal problems and preserve tooth structure.
Can a transcriptional activator known to bend DNA be functionally replaced by a sequence-directed bend in Escherichia coli? To investigate this question, a partially truncated promoter was used, deleted of its -35 region and of its CRP binding site, leaving only two Pribnow boxes as functional elements. Synthetic and naturally occurring curved DNA sequences introduced upstream from these elements could restore transcription at either one of the two natural starts. Some of these hybrid promoters turned out to be more efficient than the CRP activated wild-type gal promoter in vivo. Control experiments performed with very similar sequences devoid of any curvature produced weak promoters only. Minimal changes in the location of the centre of curvature or perturbation in the amount of curvature strongly affected the level of expression. No significant stimulation of transcription could be detected in vitro. Furthermore, both gal P1 and P2 starts could be activated in vivo but also in vitro via a properly positioned CRP binding site. This partial analogy suggests that bending induced by the cAMP-CRP complex upon binding to its site may be biologically relevant to the mechanism of transcriptional activation.
Explore the source record for details and available documents.
Instruments and methods used for data collection in the Italian multicenter case-control study of clinically diagnosed Alzheimer disease are illustrated. Details of design of the questionnaire, choice and training of the interviewers, choice of the respondent, and assessment of the quality of data collected are discussed. The text of the questionnaire is included.
Explore the source record for details and available documents.
In 1984-85, the authors assessed the reliability of surrogate respondents to provide interview data for the specific items of a case-control study of Alzheimer's disease conducted in Italy. For all questions of the interview, responses of 52 non-demented subjects were compared to responses of their next-of-kin. In 21-27% of the pairs the next-of-kin was unable to answer questions about general anesthesia, antacid drug use, and age of mother and father at index birth. However, the surrogate respondent was able to answer 45 of 57 tested items with agreement greater than 80%. Questions about use of hard liquor and behavior pattern yielded agreement of 71-75%, while those about number of jobs, and number of cigarettes per day yielded 62-63% agreement. For those who provided information about antacid drug use, agreement was poor. These findings are encouraging for the use of next-of-kin respondents in case-control studies of Alzheimer's disease or other neurologic conditions for which the subject cannot provide historical information.
A prevalence study of Huntington's chorea in Florence area in the period 1970-1979. Two clusters have been identified and the frequency of subjects heterozygote for Huntington's gene has been determined for planning Public Health intervention and the preparation of correct genetic counselling.
We conducted a case-control study of 116 patients with the clinical diagnosis of Alzheimer's disease (AD) in seven Italian centers. One hundred sixteen hospital controls and 97 population controls were matched by age, sex, and region of residence to the cases. A structured questionnaire was administered to the next-of-kin of cases and controls by trained interviewers to identify possible risk factors. Genetic, viral, toxic, immunologic, medical, surgical, and personality factors were investigated. Dementia among first- or second-degree relatives and advanced age of the mother at subject's birth (age over 40) were associated with AD. Head trauma was more frequent in cases than in either hospital or population controls, but the differences were not significant. Our data did not confirm the previously reported association with antecedent thyroid disease or family history of Down's syndrome.
The effects of GM1 ganglioside (30 mg/kg i.p.) administration for 22 days on choline acetyltransferase (ChAT) activity and noradrenaline (NA) levels in the cerebral cortex and on the acquisition of active and passive avoidance-conditioned responses were investigated in both sham-operated rats and in rats with a unilateral electrolytic lesion of the magnocellular forebrain nuclei (MFN). A statistically significant ChAT decrease in cortical areas ipsilateral to the lesion was found in saline-treated lesioned rats. In the lesioned GM1-treated rats, ChAT activity was only reduced in the frontoparietal areas and was significantly increased in the ipsilateral parietooccipital areas as well as in both contralateral regions. NA levels in the cortex were neither significantly affected by the lesion nor by GM1 treatment. The lesion impaired the acquisition of active and passive conditioned avoidance responses. GM1 treatment improved acquisition of the active avoidance response in the lesioned rats as indicated by a larger number of avoidances and a smaller number of escape failures during training in comparison with saline treatment. Ganglioside had no effect on the passive avoidance responses. These results demonstrate that GM1 administration facilitates the recovery of the cortical cholinergic system and of behavioral responses impaired by an electrolytic lesion of the cholinergic forebrain nuclei.
An epidemiological survey of amyotrophic lateral sclerosis (ALS) based on 83 patients living in the province of Florence (central Italy) showed an incidence of 0.714 X 100,000 inhabitants and a prevalence of 2.142 X 100,000 inhabitants. The disease was found to be more prevalent in males (sex ratio 1.3--1). Average age of onset was 59 years (57 +/- 4 for males and 61.6 +/- 3 for females). No particular geographical distribution was noted. 59 % of the patients presented the conventional amyotrophic form, while 10 % and 30 % were those with the bulbar and polyneuritic type, respectively. A survey of the social and economic status showed ALS to be more frequent in manual workers (P less than 0.001). Among all patients 31 % presented evidence of trauma; however only in 15 % of them could the trauma be chronically and topographically related to the onset of ALS. The presence of other diseases associated with ALS was examined but the combination found may be only casual.