Biomedical subjects

D Giorgi

Publications and source records attributed to D Giorgi.

105 records · Page 6Linked to original sources

PubMed1987

Amylase and chymotrypsinogen synthesis and secretion by the anesthetized rat pancreas.

To investigate the origin of nonparallel secretion, pancreatic juice was collected in the anesthetized rat, during infusion of [3H]phenylalanine. In the basal state, the amylase to chymotrypsinogen ratios of activities and of [3H] incorporations were 3.5 and 2.5 times higher than in the homogenate, respectively. Both ratios decreased to the value in the homogenate upon caerulein stimulation (600 ng/kg). Inhibition of protein synthesis by cycloheximide (15 ng/kg) did not alter enzyme secretion ratios, and depressed basal protein output only partly, suggesting similar secretory pathways for basal and stimulated secretion. Finally, when [3H]phenylalanine was given before anesthesia, the amylase to chymotrypsinogen ratio of incorporations was again higher in basal secretion than in homogenate, even when further protein synthesis was blocked by cycloheximide before urethane injection. Hence, basal secretion comes from a pancreatic compartment which is functional, although minor, in the conscious animal, and shows a higher rate of amylase synthesis, compared to chymotrypsinogen, than the rest of the gland. It could consist of a subpopulation of acinar cells.

Amylases↗

PubMed1986

Regulation of concentrations of mRNA for amylase, trypsinogen I and chymotrypsinogen B in rat pancreas by secretagogues.

Regulation of pancreatic gene expression by the secretory stimulants cholecystokinin-pancreozymin, caerulein and pilocarpine was studied in the rat, by using cloned cDNA probes to quantify concentrations of specific mRNAs (amylase, trypsinogen I and chymotrypsinogen B). It is concluded that long-term pancreatic stimulation results in pre-translational regulation of secretory-protein gene expression, with a preferential accumulation of RNA transcripts encoding serine proteinases, compared with that for amylase.

Amylases↗

PubMed1986

Overproduction of the first three enzymes of pyrimidine nucleotide biosynthesis in Drosophila cells resistant to N-phosphonacetyl-L-aspartate.

Drosophila cells were treated in vitro with N-phosphonacetyl-L-aspartate (PALA) which is a specific inhibitor of aspartate transcarbamylase, the second enzyme of the pyrimidine biosynthetic pathway. By stepwise selection using increasing amounts of this inhibitor, PALA-resistant (PALAr) stable clones have been isolated. Enzymatic activities of aspartate transcarbamylase, carbamyl phosphate synthetase and dihydro-orotase, borne by the same multifunctional protein, CAD, are increased 6-12-fold in these resistant clones compared with parental cells. The aspartate transcarbamylase in PALAr cells is shown by physical, kinetic and immunological criteria to be normal. The data from immunotitration and immunoblotting experiments indicate that the increased enzyme activities result from the overproduction of CAD.

Amidohydrolases↗

PubMed1986

Newly synthesized amylase, lipase and serine proteases are transported at different rates in rat pancreas.

The rates of intracellular transport of newly synthesized amylase, lipase, trypsinogen and chymotrypsinogen were compared in the anaesthesized rat pancreas by measuring their rates of secretion while keeping their relative rates of synthesis in a steady state. It is concluded that pancreatic proteins are not transported all at the same rate through the acinar cell. Among the four enzymes studied, proteolytic enzymes are transported faster than lipase, and amylase is the slowest. The relative rates of transport of these enzymes are not altered by secretory stimulation, since similar results were obtained in the basal state and under constant caerulein infusion (300 ng/kg/h).

Amylases↗

PubMed1985

Regulation of proteolytic enzyme activities and mRNA concentrations in rat pancreas by food content.

Regulation by food content of the expression of genes encoding pancreatic proteases was studied in rats fed diets containing 15%, 25% or 70% protein (w/w) (diet I, II and III). Trypsin, chymotrypsin and elastase activities in pancreas were 1.4, 2.8 and 2 times higher in diet III than in diet I whereas carboxypeptidase A level was unchanged. As compared to diet I, the pancreatic concentration of mRNAs encoding trypsinogen I and chymotrypsinogen B, measured by filter hybridization to specific cDNA probes, were found respectively 3.6 and 3.9 times higher in diet III, and 1.9 and 2.6 times higher in diet II. Elastase I mRNA concentration was 1.8 times higher in diet III, but unchanged in diet II. Procarboxypeptidase A mRNA concentration was not affected. It is concluded to a coordinate pre-translational regulation of serine protease genes expression by the protein content of diet, differing however in amplitude and sensitivity among the three species of enzymes studied.

Animals↗

PubMed1985

Pancreatic stone protein. I. Evidence that it is encoded by a pancreatic messenger ribonucleic acid.

We have previously shown that the pancreatic stone protein (PSP) is an inhibitor of calcium carbonate crystal growth and may participate in the stabilization of the normally supersaturated pancreatic juice. Our aim in this study was to determine if PSP is a normal secretory product of the human pancreas by determining if the normal human pancreas contains a messenger RNA coding for PSP. Human pancreatic messenger RNAs were used to direct protein synthesis in a cell-free translation system. Immunoprecipitation of translation products with a monospecific antibody directed against the PSP yielded a product migrating as a single homogeneous band on sodium dodecyl sulfate-polyacrylamide gels. This product has a molecular weight of 16,000, the value expected for pre-PSP. Products selected by immunoprecipitation with antitrypsin-1 antibodies also migrated as a single band, with a molecular weight of 27,000. It is concluded that a messenger RNA coding for pre-PSP, distinct from the messenger RNA coding for pretrypsinogen, is present in human pancreas. These results support the hypothesis that PSP is a molecular entity, and not a degradation product of trypsinogen 1 or another pancreatic protein.

Animals↗

PubMed1985

Human erythrocyte hexokinase deficiency: a new variant with abnormal kinetic properties.

A 14-month-old child who had a haemolytic episode when he was 5 years old, and with psychomotor retardation, was found to have decreased red cell hexokinase activity. The mutant enzyme was characterized by an increased affinity for glucose associated with an increased inhibition constant for glucose-1,6-diphosphate. Affinity for Mg ATP2-, heat stability and pH-optimum were normal. The isozymic pattern of the red cell enzyme was normal but all the molecular forms were present in reduced amounts. The kinetics of decay of hexokinase during cell ageing was also normal. Glucose consumption of the hexokinase deficient cells was 60-65% of the controls while the amount metabolized through the hexose monophosphate shunt was unchanged. Red cell 2,3-diphosphoglycerate and glucose-6-phosphate levels were normal in the proband but reduced in the erythrocytes of his parents, who were heterozygous for the defect but had normal haematological data. Comparison with the 13 previously reported cases of hexokinase deficiency confirms the broad phenotypic variability that characterizes this disorder.

Blood Glucose↗

PubMed1984

Apple II PASCAL programs for molecular biologists.

A collection of PASCAL programs designed for the Apple II microcomputer is presented. These DNA sequence handling and analysis programs are interactive and may be used even by people with no computer experience. The package allows the user to enter a sequence from the keyboard, to modify it, to generate the reverse complement, to create new sequences from parts of other ones, to display or print sequences in various formats. Some analysis tasks are also performed: Translation, searches for restriction sites, for homology with subsequences, either perfect or with an adjustable match percentage. In addition, two programs are also included: The first one allows DNA data sequences generated with a BASIC program under the CP/M operating system to be used with these PASCAL programs. The second one is designed for the automatic assembly of DNA fragments sequences, obtained with the GILBERT-MAXAM or M13 techniques, into a complete sequence.

Amino Acid Sequence↗

PubMed1984

Regulation of amylase messenger RNA concentration in rat pancreas by food content.

Regulation of the expression of pancreatic amylase genes was studied by comparing groups of rats fed diets with high (75%), intermediate (20%) and low (11%) carbohydrate content. Animals on the high carbohydrate diet had nine times as much amylase mRNA as those on low carbohydrate diet, and twice as much as the intermediate group, as determined by filter hybridization of equal amounts of total pancreatic RNA to an excess of a cloned rat amylase cDNA probe. Parallel results were obtained when levels of translatable amylase RNA were compared by means of an RNA-dependent rabbit reticulocyte cell-free system. Amylase mRNA-directed synthesis represented 35% of the total in the high carbohydrate group, 4% in the low group and 14% in the intermediate group. Relative rates of amylase synthesis, determined 30 min after [3H]phenylalanine injection, followed the same pattern. While 37% of total was incorporated into amylase in the high carbohydrate group, only 8% was incorporated in the low carbohydrate group, as compared with 22% in the intermediate group. These data indicate that modifications of diet composition alter the expression of pancreatic amylase genes as a consequence of changing the level of their transcript, and that pancreatic amylase production is mostly regulated at the pre-translational level.

Amylases↗

PubMed1984

Infantile spasms--long term results of ACTH treatment.

From a series of 230 subjects with infantile spasms (I.S.) observed from 1955 to 1982, 191 cases with sufficient data on follow-up and evaluation were selected. The period of follow-up in 100 subjects ranged from 3 months to 3 years and was more than 3 years in the remaining 91 patients. Disappearance of spasms and normal psychomotor development was observed in 34 of the 61 idiopathic and post-infectious cases. In 130 subjects with secondary forms normal psychomotor development was observed in only two patients; disappearance of spasms was noted in 54 and normalisation of the EEG in 13 subjects. Satisfactory long term results can be obtained with a relatively low dose of corticotropin in a considerable number of patients having idiopathic and post-infectious forms of I.S. To obtain the best results treatment should be started as soon as possible.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Forty-five consecutive patients (33 men and 12 women; 53 +/- 6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamond's algorithm) was low (45.6% +/- 12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3% +/- 10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4% +/- 4.3% (p < 0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3% +/- 5.5% (p < 0.003), a level that appeared significantly higher than that of model 2 (p < 0.016). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

Adult↗

PubMedDate not supplied

General practitioners and mammographic screening uptake: influence of different modalities of general practitioner participation. Working Group.

AIMS AND BACKGROUND: To compare the impact of different modalities of general practitioner (GP) involvement, including the introduction of target payments, on the attendance rate of organized population-based screening programs for breast cancer in Italy. STUDY DESIGN: The study was conducted between 1994 and 1996 in four Italian cities where mammographic screening programs are active: Caltanissetta (CL), Firenze (FI), Modena (MO) and Torino (TO). The impact on attendance rate of different invitation strategies based on active GP involvement was tested in each center. The additional effect of economic incentives was also assessed. The incentives were proportional to the level of compliance attained by each GP and weighted by the size of his eligible patients' list. RESULTS: In the Firenze project, an invitation signed by the GP and the project co-ordinator attained a statistically significant higher participation (difference: 4.2%, chi2 = 7.42, P = 0.006). In Caltanissetta and Torino there was a significant increase of about 7% in the response rate to the postal reminder in the groups contacted by the GPs. No difference was observed in the Modena project between the two groups. CONCLUSIONS: The main contributions of GP involvement can be: "cleaning up" the invitation lists, especially when computerized archives with the mammographic history of the target population are not available; increasing the women's participation by signing the invitation letter, by counseling and active participation in the invitation phase; co-operating in the reminder phase by recalling women non responders at first invitation. The offer of target payment had a certain impact on the screening uptake, but not easily distinguishable from GP signature of the invitation letter; further studies of appropriate design should be planned. Organizational factors, such as availability of a list of non-responders, might be crucial in order to enhance the effect of the GPs' action.

Family Practice↗

PubMedDate not supplied

Breast cancer screening: characteristics and results of the Italian programmes in the Italian group for planning and evaluating breast cancer screening programmes (GISMa).

In 1990, GISMa (Italian Group for planning and evaluating Mammographic Screening - Gruppo Italiano per la pianificazione e la valutazione dei programmi di Screening Mammografico), a working group of operators (radiographers, radiologists, epidemiologists, clinicians, surgeons) involved in screening programmes ongoing in Italy, was created within the Italian School of Senology. The aim of this study is to illustrate data, presented at the GISMa meeting held in April 1994, concerning the characteristics of each programme and some early indicators of effectiveness. To assess these parameters (concerning compliance level, recall rate, benign/malignant biopsy ratio, detection rate, stage distribution, nodal involvement and number of cancers with a diameter under 1 cm, rate of cancer, etc.), 'acceptable' and 'desirable' standards obtained from Italian and North-European cancer screening experiences have been adopted. Most programmes have shown an acceptable standard for most of the indicators, and many of them have attained desirable levels. In most screening programmes the occurrence of interval cancers has not yet been measured, but all centres have (or are working to set up) a systematic active procedure to collect the data. The results indicate that common guidelines can be adopted, even when working in very heterogeneous contexts, and that it is possible to achieve a very high effectiveness and efficacy level. As regards quality control and cost/benefit issues, the goal of extending centralised, population-based screening programmes to other Italian regions becomes a priority.

Aged↗

PubMedDate not supplied

Long-term sequelae of breast cancer surgery.

BACKGROUND: Quality of care is today a major issue in oncology, and much attention is given to research on the outcome of breast cancer care. Too little attention has been devoted in the scientific literature to the consequences of treatment in long-term survivors, and in particular to the possible side effects. The specific aim of this contribution is to present population-based data about the long-term impact of breast cancer care in women who had an incident cancer in 1985/1986. PATIENTS AND METHODS: The cases are 476 breast cancers incident in the City of Florence in 1985-86. Women still living 5 years later were invited to have an interview and a physical examination. Lymphedema, peripheral nerve lesions and damage to the shoulder were assessed. RESULTS: Of the 346 5-year survivors, 238 accepted our invitation: 35.2% of the women reported some early postoperative sequelae, 30.2% had a chronic lymphedema and 18.9% a shoulder deficit. Comparing breast-conserving surgery with radical mastectomy, the risk of chronic lymphedema (OR = 1.62; 95% C1: 0.91-2.88) and other lesions was higher for women who had a radical surgery. Women who had a breast-conserving surgery more often reported an early lymphedema (OR = 1.60; 95% Cl: 0.88-2.88). CONCLUSIONS: The proportion of women who complained of (or manifested at the physical examination) a minor or major disability of the arm in our study was high. The impact of these functional problems in terms of quality of life should also be assessed, but it is our impression that there is need for much greater attention to the issue of long-term survivor sequelae.

Adult↗

PubMedDate not supplied

[Assessment of diagnostic accuracy of mammography carried out for secondary prevention. Results of a test with a sample caseload conducted by 75 Italian radiologists].

PURPOSE: To report the results of a test performed by 75 volunteer radiologists involved in screening program in Italy. MATERIAL AND METHODS: The test includes 12 screening detected cancers and 6 cancers (4 screening detected and 2 interval lesions) with minimal signs at review of a previous negative mammogram. Data on previous experience in mammography (years of activity, years of screening activity, total number of mammograms read and number of mammograms read per year) were also collected. RESULTS: Standards for passing the test were at least 83.3% for sensitivity for screening detected cancers and at most 30% for recall rate among negative cases. Mean sensitivity was 83.9% (median 83.3%, range 50-100%) and mean recall rate was 16.3 (median 14.4%, range 3.8-42.4%). In all, 44 radiologists (58.7%) passed the test. On average 1.4 of 6 cancers with minimal signs were correctly identified. According to readers' experience (at least 5 years in mammographic activity, at least 3 years in screening mammography, at least 10,000 total mammograms read, at least 5,000 per year) radiologists were classified as expert (13) or not (62): no difference in test performance was observed between the two groups. The only significant association occurred for years of mammographic activity and sensitivity. DISCUSSION AND CONCLUSIONS: Test results suggest the need for proper training of radiologists prior to involvement in a screening program. Seeding proficiency tests with cancers with minimal signs was of no benefit as far as evaluation is concerned.

Aged↗