PubMed Health⌕ Search

Biomedical subjects

S Petralia

Publications and source records attributed to S Petralia.

At least 19 recordsLinked to original sources

The photochemistry of flutamide and its inclusion complex with beta-cyclodextrin. Dramatic effect of the microenvironment on the nature and on the efficiency of the photodegradation pathways.

The photochemistry of the anticancer drug flutamide (FM), 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide, in homogeneous media and in the beta-cyclodextrin (beta-CD) cavity has been investigated. The photoreactivity of the free molecule has been rationalized on the basis of an intramolecular nitro to nitrite rearrangement followed by cleavage of the nitrite intermediate. The twisted geometry of the nitro group with respect to the aromatic plane plays a key role in triggering such a photoprocess. Incorporation of FM in the beta-CD cavity leads to dramatic effects on both the efficiency and the nature of the photochemical deactivation pathways of the guest molecule. A 20-fold increase in the FM photodecomposition quantum yield and the formation of photoproducts originated by both reduction of the nitro group and cleavage of the amide bond were observed in the presence of the macrocycle. Such a behavior cannot be attributed exclusively to the micropolarity of beta-CD and/or to its role as a reactant. The induced circular dichroism spectra and the nature of the photoproducts formed in these experimental conditions provide indications that the photoreactivity in the beta-CD microenvironment could likely be mediated by structural changes of FM upon complexation.

Antineoplastic Agents, Hormonal↗

Mortality of a police cohort: 1950-1990.

This study presents findings from an updated retrospective cohort mortality study of male police officers from January 1, 1950 to December 31, 1990 (n = 2,593; 58,474 person-years; 98% follow-up). Significantly higher than expected mortality rates were found for all cause mortality (Standardized mortality ratio [SMR] = 110; 95% confidence interval [95% CI] = 1.04-1.17), all malignant neoplasms (SMR = 125; 95% CI = 1.10-1.41), cancer of the esophagus (SMR = 213; 95% CI = 1.01-3.91), cancer of the colon (SMR = 187; 95% CI = 1.29-2.59), cancer of the kidney (SMR = 2.08, 95% CI = 100-3.82), Hodgkin's disease (SMR = 313; 95% CI = 1.01-7.29), cirrhosis of the liver (SMR = 150; 95% CI = 1.00-2.16), and suicide (SMR = 153; 95% CI = 1.00-2.24). All accidents were significantly lower (SMR = 53; 95% CI = 0.34-0.79). Mortality by years of police service showed higher than expected rates for (1) all malignant neoplasms in the 1- to 9-years-of-service group; (2) all causes, bladder cancer, leukemia, and arteriosclerotic heart disease in the 10 to 19-year group; and (3) colon cancer and cirrhosis of the liver in the over 30 years of service group. Hypotheses for findings are discussed.

Adult↗

Environmental risk factors of breast cancer.

Breast cancer is women's most ubiquitous cancer. The role of dietary factors is controversial, but there is limited evidence for such occupational risk factors as employment in the pharmaceutical industry and as a beautician. Ionizing radiation probably increases the risk. Exposure to chlorinated hydrocarbon pesticides, chlorinated solvents, and polychlorinated biphenyls may be risk factors, although the evidence is insufficient. Data on low-frequency electromagnetic fields are inconclusive. Tobacco smoking may be a risk factor, but the effect may depend on N-acetyltransferase 2 genetic polymorphisms. There are yet unidentified determinants, probably environmental, that may act via estrogenic activity or through other mechanisms. The etiology may vary according to the joint estrogen and progesterone receptor status of the tumor. P53 mutation frequency varies considerably in breast cancer populations, which may reflect variation in exogenous exposures. Epidemiology research on breast cancer needs to consider subtypes of the disease, lifetime exposure assessment, host susceptibility, and adjustment for reproductive and menstrual history.

Breast Neoplasms↗

Liver is not the unique site of synthesis of beta 2-glycoprotein I (apolipoprotein H): evidence for an intestinal localization.

Apolipoprotein H is a protein of about 50 kilodaltons, structurally related to the regulators of the complement activation family. Its physiological function is poorly understood but it has been implicated in lipid metabolism and coagulative pathways. The major site of synthesis is thought to be the liver. Several reports indicate that apolipoprotein H is the antigen of the antiphospholipid antibodies and also behaves as an acute-phase reactant. Moreover, 40% of plasma apolipoprotein H is associated with very low-density lipoprotein, high-density lipoprotein, and postprandial chylomicrons. In this study we investigated other sites of synthesis by reverse transcription/polymerase chain reaction and we found apolipoprotein H mRNA expression in intestinal cell lines and tissues. Immunohistochemistry was performed on various fresh and paraffin-embedded tissues and apolipoprotein H was immunolocalized in the cytoplasm of hepatocytes and epithelial cells from colon and jejunum. This study indicates that apolipoprotein H is expressed at both mRNA and protein levels in enterocytes.

Apolipoproteins↗

Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons.

The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27 and PACAP38, are two neuropeptide hormones related to the vasoactive intestinal peptide/secretin/ glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been identified in cultured cerebellar granule cells. Using the reverse transcription-polymerase chain reaction methodology, we demonstrated the expression of the PACAP-R and PACAP-R-hop mRNAs in cultured granule cells. When grown in the absence of serum or in low K+ concentrations, these neurons underwent apoptosis, a naturally occurring process characterized by cell shrinkage and internucleosomal DNA cleavage. We used these models of programmed cell death to study the relationship between PACAP receptor activation and neuronal apoptosis. Treatment with PACAP27 and PACAP38 reduced the development of apoptosis in a dose-dependent manner. The neuroprotective activity of PACAP was mimicked by high concentrations of vasoactive intestinal peptide or forskolin but not by carbamylcholine. Thus, we suggest that the activation of type I PACAP receptors may contribute to the survival of cerebellar granule neurons.

Animals↗

A comparative evaluation of police suicide rate validity.

The authors assessed sensitivity, specificity, and predictive value of official police suicide rates and compared them to municipal workers. Deaths officially classified as suicide, accidental, and undetermined were submitted to a panel of medical examiners for validation. Six cases originally in the accident and undetermined rubric were reclassified as suicide. Official police suicide rates had less sensitivity (83.3% compared to 92.3%) of actual suicides than municipal worker rates. Police suicide rates also showed a lower negative proportion than municipal worker rates (86.2% compared to 98.7%). A generalizable sensitivity proportion equation for assessing suicide rates in other police groups is presented.

Humans↗

Constitutively expressed c-myb abrogates the requirement for insulinlike growth factor 1 in 3T3 fibroblasts.

The proto-oncogene c-myb, whose expression is usually limited to cells of the hematopoietic lineages, can be expressed in fibroblasts if placed under the control of a constitutive promoter, such as the simian virus SV40 early promoter. 3T3 cells carrying a constitutively expressed human c-myb were found to grow in 1% serum or in a serum-free, platelet-derived growth factor-supplemented medium, whereas the parent cell line, BALB/c 3T3, needed insulinlike growth factor 1 (IGF-1) in addition to platelet-derived growth factor for growth. myb-carrying cells, however, could not grow in platelet-poor plasma. In fibroblasts, therefore, a constitutively expressed c-myb can abrogate the requirement for platelet-poor plasma or IGF-1. When 3T3 cells constitutively expressed both c-myc and c-myb, they could grow in serum-free medium without added growth factors. The ability of c-myb to abrogate in fibroblasts the IGF-1 requirement seems to be due to its ability to induce overexpression of IGF-1, as indicated by an increase in steady-state levels of IGF-1 mRNA. These results have some important implications; for instance, they suggest a commonality of pathways for entry into S phase in different cell types and the possibility of a myb-like or myb-equivalent gene product of critical importance for entry of fibroblasts into S phase.

Animals↗

The promoter of the proliferating cell nuclear antigen (PCNA) gene is active in serum-derived cells.

mRNA levels for the Proliferating Cell Nuclear Antigen (PCNA) gene are growth regulated. PCNA promoters of different lengths were used to drive a linked reporter, the cDNA for human thymidine kinase (TK). After transfection into TK ts13 cells, stable cell lines were obtained. Regardless of promoter length, in all cell lines the levels of TK mRNA were roughly similar in serum-deprived and serum stimulated cells, confirming, by an independent method, that the growth regulation of PCNA mRNA levels doe not depend on the 5' flanking sequence of the PCNA gene.

Animals↗

Oncogenes in growth and development.

Oncogenes play a major role in the control of proliferation in animal cells. Because the growth of cell populations is regulated by the stimulatory and inhibitory growth factors in the environment, we have attempted in this review to relate the function of oncogenes to the mechanism of action of growth factors. This correlation allows a description of the cell cycle that rests on a molecular basis and in which protooncogenes figure prominently as the cellular messengers of the environmental growth stimuli.

Animals↗

In vitro lymphocyte sensitivity test to methisoprinol in different pathological conditions.

The present paper describes an in vitro study with Methisoprinol, carried out by means of various lymphocyte sensitivity tests in different pathological conditions. Methisoprinol does not exert any effect--neither on responsiveness nor on lymphocyte function--in healthy subjects, while in subjects with immunodepressive pathology the drug is capable of increasing these parameters either alone (rosettes) or in conjunction with mitogens (rosetting) at doses between 50 and 100 micrograms/ml.

Brain Neoplasms↗

Increase in cellular RNA in cells infected with DNA oncogenic viruses.

The amount of RNA per cell has been measured by flow microfluorometry in cultured cells stimulated by serum or infected with DNA oncogenic viruses (SV40, polyoma virus, and adenovirus). While all four agents stimulate, although to a different extent, cellular DNA synthesis in quiescent cells, the accumulation of cellular RNA varies. Serum, SV40, and polyoma virus cause a marked increase in total cellular RNA that is already apparent in G1 cells before entry into S. On the other hand, adenovirus 2, while capable of stimulating cellular DNA synthesis, fails to detectably increase the amount of RNA per cell. These results suggest that adenovirus 2 may act on quiescent cells through mechanisms different from those of serum, SV40, or polyoma virus.

Acridines↗

[Stress/strain ratio of the left ventricle in systole. Influence of age and of some drugs (author's transl)].

By testing with echocardiographic techniques on healthy hearted human subjects, it is shown that the myocardium elastic modulus, defined as the ratio between the equatorial stress in the left ventricular wall and the strain of the left ventricular cavity, results to be independent from the age of subjects at rest. In healthy subjects the treatment with vasoxine, a vessel-constrictor drug, causes an increase in the elastic modulus, the treatment with isoproterenol, an inotropic agent, makes the elastic modulus decrease, whereas the treatment with peritrate, a nitroderivative, does not modify this modulus. In conclusion this parameter, though it cannot be considered a cardiac contractility index, yet it may be utilized to characterize the left ventricular functional state. The alterations caused by the use of vasoxine and isoproterenol in cardiac frequency, left ventricular geometry and arterial pressure, in the examined subjects, are comparable with the alterations reported in the recent literature.

Adult↗

[Measurement of the stress deformation ratio in the left ventricle in systole].

Thirty-three subjects, fourteen of which with normal heart, ten with aortic insufficiency and nine with myocardiopathy, were studied by echocardiography and sfigmomanometric arterial pressure measurements. The ejection fraction EF, the left ventricular equatorial wall stress sigma, the corresponding left ventricular strain epsilon and the ratio E = sigma/epsilon have been determined for all subjects. The mean values of these quantities, at the onset of ventricular systole, for normal hearts are: EF = 0.67 +/- 0.05; sigma = (2.67 +/- 0.41) . 10(5) dine/cm2; E = (0.99 +/- 0.15) . 10(6) dine/cm2; for patients with aortic insufficiency: EF = 0.51 +/- 0.09; sigma = (2.74 +/- 1.10) . 10(5) dine/cm2; E = (1.51 +/- 0.69) . 10(6) dine/cm2; for patients with miocardiopathy: EF = 0.41 +/- 0.06; sigma = (4.36 +/- 2.08) . 10(5) dine/cm2; E = (3.20 +/- 1.19) . 10(6) dine/cm2. After a discussion on the significance of sigma and E parameters, it is inferred that E may be a useful measure of ventricular function. This parameter is different for distinct cardiac diseases and, within the limits of the same disease, probably will change according to seriousness.

Adolescent↗

[Ecographic results of mitral commisurotomy (author's transl)].

Echocardiographic studies were performed both before and after commissurotomy on fifteen subjects affected by non-calcified mitral stenosis. The amplitude CE of the anterior leaflet dis placement, the slope of the CD and EF intervals, the amplitude of the A-wave, the ratio FA/DE and the reciprocal position of the anterior and posterior leaflet echoes were measured on the echographic records. These data were compared with the values obtained in ten normal subjects. After commissurotomy, the slope of the CD interval and most evidently that of the EF interval increased (the last one by a factor of 3), and the area of the mitral opening was found to be more than 9% larger. The A-wave reappeared clearly in 30% of the operated patients, and the outline of the posterior leaflet was no longer inscribed in the anterior leaflet diastolic curve in all cases; the amplitude CE was unchanged.

Adult↗