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Biomedical subjects

A Piazza

Publications and source records attributed to A Piazza.

At least 37 records · Page 2Linked to original sources

Uralic genes in Europe.

We have analysed data of three European populations speaking non-Indoeuropean languages: Hungarians, Lapps, and Finns. Principal coordinate analysis shows that Lapps are almost exactly intermediate between people located geographically near the Ural mountains and speaking Uralic languages, and central and northern Europeans. Hungarians and Finns are definitely closer to Europeans. An analysis of genetic admixture between Uralic and European ancestors shows that Lapps are slightly more than 50% European, Hungarians are 87% European, and Finns are 90% European. There is basic agreement between these conclusions and historical data on Hungary. Less is known about Finns and very little about Lapps.

Europe

Regional distribution of cystic fibrosis linked DNA haplotypes in Italy, a collaborative study.

In view of the reported variations of cystic fibrosis (CF) associated haplotypes among populations, a detailed analysis of the distribution of two tightly linked DNA markers (Xv-2c and KM.19) in 18 Italian regions was performed. Haplotypes were determined for 405 CF chromosomes carrying the mutation, and showed significant heterogeneity between the North, Center, and South of Italy and the island of Sardinia. KM.19/PstI Restriction Fragment Length Polymorphism (RFLP) showed significant heterogeneity in these four areas, and was statistically correlated with the geographic distribution of the disease, while Xv-2c/TaqI polymorphism, like the haplotypes of normal chromosomes, was more uniformly distributed over the same four areas. Correlation coefficients between the markers and the mutation have been used to obtain additional indications on the physical distance between the markers and the fibrosis locus.

Cystic Fibrosis

[Effects of chronic administration of nifedipine on echo-Doppler parameters of left ventricular filling in hypertensive patients].

This study aimed determining the chronic effects of nifedipine (N) on left ventricular filling in 25 patients (mean age 55) with mild to moderate arterial hypertension. M-mode, B-mode and pulsed Doppler measurements were performed at baseline, after 30 min from administration of sublingual N (10 mg) and after 6 months of therapy with slow release N (max dose: 60 mg die). Acute and chronic N reduced significantly both systolic (p less than 0.001) and diastolic pressure (p less than 0.001). At the end of the treatment with slow release N, and septal wall thicknesses had a slight but significant decrease (p less than 0.01). Diastolic and systolic dimension were not modified. Left ventricular mass index decreased significantly from 141 +/- 34 to 130 +/- 31 g/m2 (p less than 0.05). The Doppler-derived diastolic filling indexes (peak E, ratio peak E/A,E deceleration) were abnormal at baseline, and had a significant increase after sublingual and chronic therapy. Changes in left ventricular mass index and diastolic filling indexes were not correlated. A significant correlation was found between peak E changes after acute and chronic N administration (r = 0.732 and p less than 0.001). The results of this study demonstrate that both acute and chronic administration of N modify transmitral flow velocity pattern, suggesting that, in hypertensive patients, left ventricular filling abnormalities are partly dynamic and reversible. Our findings also demonstrate that acute N effects may predict the chronic results.

Adult

B cells from chronic lymphocytic leukemia (CLL) patients are strong inducers of proliferation and major histocompatibility complex (MHC)-unrestricted [natural killer (NK)-like] cytotoxicity in normal T-lymphocytes.

We studied the ability of chronic lymphocytic leukemia (CLL) B cells to stimulate proliferation and major histocompatibility complex (MHC)-unrestricted [natural killer (NK)-like] cytotoxicity in a mixed lymphocyte tumor-cell culture (MLTC). CLL-derived B cells induced a significantly higher proliferative response than did B cells from healthy normal donors. Comparable levels of interferon and interleukin-2 production were detected in the mixed lymphocyte cultures (MLC) set up with normal B cells from healthy donors and in MLTC. Higher levels of NK-like cytotoxic activity were induced after stimulation with CLL than with normal B cells in nonlytic precursors. Inhibition experiments with specific monoclonal antibodies indicate that the NK-like response in MLTC is attributable to HLA class II antigens, which are expressed at comparable levels on CLL and normal B cells. Percoll gradient centrifugation of the MLC and MLTC recovered cells demonstrated that the NK-like effectors in both types of cultures were blast-transformed, highly mitotic cells.

B-Lymphocytes

Cytotoxic effectors in human peripheral blood mononuclear cells induced by a mannoprotein complex of Candida albicans: a comparison with interleukin 2-activated killer cells.

In this study, the major histocompatibility complex-unrestricted cytotoxic effectors elicited in human peripheral blood mononuclear cells (PBMC) by a mannoprotein (MP) component from the cell wall of the human indigenous microorganism Candida albicans have been compared with those obtained by stimulation with interleukin 2. (Interleukin 2-activated killer cells: LAK). It has been found that MP-induced lytic effectors were substantially similar to LAK in potency, target specificity, and type of precursor/effector cells. In both cases, natural killer (NK)-susceptible and NK-resistant targets as well as fresh tumor (glioma) cells were efficiently killed by a population of effectors showing a predominant CD3-, CD16+ phenotype. However, the precursors of MP-induced killers were highly sensitive to the lysosomotropic toxic drug L-leucine methyl ester (Leu-OME) whereas the generation of LAK cells was unaffected by this drug. The Leu-OME sensitivity of MP-induced cytotoxicity generation was not due to a nonspecific effect on antigen-presenting cells or inhibition of cell proliferation. In addition, the generation of MP-induced killer cells was totally abrogated by treatment with CD16 antibodies and complement, whereas a minor but significant fraction of LAK precursors was not susceptible to the above treatment. These results indicate that a defined component(s) of the cell wall of C. albicans has some properties of biological response modifiers in cultures of human PBMC in vitro.

Antigens, Surface

HLA antigens and neuroleptic response in clinical subtypes of schizophrenia.

The frequency of HLA antigens of A and B loci was examined in a carefully selected sample of 91 schizophrenic patients from central Italy. This population showed no increase in antigens compared with the control group. However, in agreement with previous studies, a slight increase in A1 was observed in the hebephrenic subgroup and, in a lesser extent, an increase of A2 was found in the paranoid subgroup. Although these increases are more prominent when the subgroups are compared and tend to support the case for genetic heterogeneity, they fail to reach statistical significance. Response to neuroleptic treatment was studied in an attempt to further subdivide the clinical subgroups. A1-negative and A2-positive paranoid patients demonstrated a statistical better response to neuroleptics. The findings suggest that schizophrenia should be considered a heterogenous disease and that response to neuroleptics can be employed as an instrument of biological subclassification.

Antipsychotic Agents

Changes of immunological patterns of human cancer cells treated in vitro with a triazene compound.

Previous experimental evidence indicates that immunogenicity of mouse tumor cells can be increased by treatment with dacarbazine and other triazene compounds. The present studies have been conducted on the human cell lines H125 (lung cancer), 1246 (melanoma), X3 (EBV-immortalized B cells) subjected to in vitro treatment with 4 (3-methyl-1-triazeno) benzoic acid potassium salt (MTBA). Untreated or drug-treated sublines were tested for susceptibility to allogeneic NK effector cells, either non-stimulated or pretreated with beta-Interferon. In the case of X3 cell line and its MTBA-treated subline the expression of the EBV-associated antigens and the capability of eliciting autologous cytotoxic T lymphocytes (CTL) were also investigated. The results suggest that a modification of membrane antigenic pattern could be induced by MTBA treatment in terms of changes of cell susceptibility to cell-mediated lysis, expression of EBV-related antigens and capability to elicit autologous CTL.

Antigens, Differentiation, B-Lymphocyte

[Modification of left ventricular filling after acute administration of nifedipine in hypertensive patients. Doppler echocardiographic study].

This study was undertaken to determine the acute effects of nifedipine on left ventricular filling, examined by Doppler echocardiography in patients with arterial hypertension and normal left ventricular systolic function. Twenty-seven patients with mild to moderate systemic hypertension, and 18 normotensive subjects were studied. Pulsed Doppler, M-mode and B-mode measurements were performed before and 30 min after sublingual nifedipine administration (10 mg). Peak E, peak A, area A, area E, ratio area A/area E, E deceleration and E acceleration time were measured. Before administering nifedipine, some of these diastolic filling parameters were significantly different in the hypertensive patients as compared with normal subjects. After nifedipine, in patients with arterial hypertension, peak E and area E increased significantly (p less than 0.01), while ratio peak A/E and ratio area A/area E showed a significant decrease (p less than 0.001). No significant changes were observed in normal subjects. The result of this study demonstrates that the acute administration of nifedipine modifies transmitral flow velocity pattern in hypertensive patients, suggesting that the left ventricular filling abnormalities are in part dynamic and reversible.

Adult

[Effects of digitalis on the left ventricular filling phase in the normal and ischemic heart. Angiographic study in man].

The effects of digitalis on the left ventricular diastolic phase are very scant. In order to gain a better insight into this problem, we measured the hemodynamic effects of an intravenous injection of K-strophantidin (0.005 mg/kg in a bolus given within 5-10 min) during the diastolic phase in 9 normal male subjects and in 9 male patients with coronary artery disease (CAD), maintaining a normal overall ejection fraction despite of the presence of some hypokinetic segments. Administration of K-strophantidin decreased significantly in normal controls the left ventricular volumes at 1/3, 1/2, 2/3 of the diastolic phase, whereas it did not produce significant change in CAD patients. Digitalis decreased the first and increased the second filling peak of the volumetric variable dV/dt in the normal controls, but not in the CAD patients. In the latter group the 2 peaks before digitalis administration were similar. The effects of digitalis on the dV/dt measured during the second filling peak were significantly different in the 2 groups. The increments of pressure in middle and end diastole in CAD patients were significantly greater than those observed in normal controls. Results of the present study suggest that digitalis has a negative influence on the left ventricular filling phase both in normal and CAD subjects. In fact digitalis modifies in normals the pattern of the left ventricular filling phase whereas it induces an untoward increase in the middle and end diastolic pressure in CAD patients.

Adult

Trypsin digestion of junctional sarcoplasmic reticulum vesicles.

A putative constituent of the junctional processes, connecting the terminal cisternae of sarcoplasmic reticulum and the transverse tubules of skeletal muscle fibers, is a greater than or equal to 350,000-dalton (Da) protein that displays ryanodine binding and Ca2+ channel properties. Ryanodine modulation of Ca2+ fluxes suggests that the ryanodine receptor and calcium channel are integral parts of one functional unit corresponding to the greater than or equal to 350,000-Da protein [Inui, M., Saito, E., & Fleischer, S. (1987) J. Biol. Chem. 262, 1740-1747; Campbell, K. P., Knudson, C. M., Imagawa, T., Leung, A. L., Sutko, J. L., Kahl, S. D., Raab, C. R., & Madson, L. (1987) J. Biol. Chem. 262, 6460-6463]. We subjected vesicular fragments of junctional-cisternal membrane to stepwise trypsin digestion. The greater than or equal to 350,000-Da protein is selectively cleaved in the early stage of digestion, with consequent disappearance of the corresponding band in electrophoretic gels. The Ca2+-ATPase is cleaved at a later stage, while calsequestrin is not digested under the same experimental conditions. While the Ca2+-ATPase yields two complementary fragments that are relatively resistant to further digestion, the greater than or equal to 350,000-Da protein yields fragments that are rapidly broken down to small peptides. Under conditions producing extensive digestion of the greater than or equal to 350,000-Da protein, the junctional processes are still visualized by electron microscopy, with no discernible alterations of their ultrastructure. The functional properties of the Ca2+ release channel are also maintained following trypsin digestion, including blockage by Mg2+ and ruthenium red and activation by Ca2+ and nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reconstruction of human evolution: bringing together genetic, archaeological, and linguistic data.

The genetic information for this work came from a very large collection of gene frequencies for "classical" (non-DNA) polymorphisms of the world aborigines. The data were grouped in 42 populations studied for 120 alleles. The reconstruction of human evolutionary history thus generated was checked with statistical techniques such as "boot-strapping". It changes some earlier conclusions and is in agreement with more recent ones, including published and unpublished DNA-marker results. The first split in the phylogenetic tree separates Africans from non-Africans, and the second separates two major clusters, one corresponding to Caucasoids, East Asians, Arctic populations, and American natives, and the other to Southeast Asians (mainland and insular), Pacific islanders, and New Guineans and Australians. Average genetic distances between the most important clusters are proportional to archaeological separation times. Linguistic families correspond to groups of populations with very few, easily understood overlaps, and their origin can be given a time frame. Linguistic superfamilies show remarkable correspondence with the two major clusters, indicating considerable parallelism between genetic and linguistic evolution. The latest step in language development may have been an important factor determining the rapid expansion that followed the appearance of modern humans and the demise of Neanderthals.

Archaeology

A genetic history of Italy.

Statistical techniques for displaying the geographical distribution of many genes in few synthetic images have been used to represent the various patterns of gene frequencies in Europe and in the world (Menozzi et al. 1978; Piazza et al. 1981 a). It has also been shown that such synthetic displays are particularly useful in detecting clines of genetic differentiation associated with movements of populations like those accompanying the Neolithic expansion of farmers from the Near East or, in more recent times, the putative diffusion of Indo-European-speaking populations (Ammerman & Cavalli-Sforza, 1984; Gimbutas, 1973). In this paper we use the same combination of statistical and graphical techniques to study the genetic structure of Italy, a European country whose unity of people and cultures was quite a recent event. The possibility of studying genetic differentiation in a small geographical area is tested and trends of genetic differences are tentatively interpreted in terms of historic and linguistic knowledge. The few demographic pieces of information taken from historical sources and compared with linguistic records support the hypothesis that the genetic structure of Italy still reflects the ethnic stratification of pre-Roman times.

Blood Group Antigens