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Biomedical subjects

S Silva

Publications and source records attributed to S Silva.

At least 19 recordsLinked to original sources

Resting blood pressure and thermal pain responses among females: effects on pain unpleasantness but not pain intensity.

In order to investigate the influence of resting blood pressure on thermal pain responses among females, this experiment studied 21 pain-free, normotensive females (mean age 23) classified as having high (HBP) vs. low blood pressure (LBP) based on a median split of resting blood pressure collected prior to thermal testing. All subjects then underwent thermal pain testing, including determination of pain threshold and tolerance followed by verbal descriptor ratings of the intensity and unpleasantness of suprathreshold thermal stimuli, ranging from 45 to 49 degrees C. Thermal stimuli were delivered to the volar forearm and the ipsilateral face using a 1 cm2 contact thermode. Results indicated that the blood pressure groups did not differ in thermal pain threshold or tolerance or on ratings of the intensity of suprathreshold thermal stimuli. However, the HBP group provided significantly lower ratings of thermal pain unpleasantness than the LBP group (P < 0.01). These data indicate that resting blood pressure is inversely associated with pain sensitivity among females, but this relationship may be selective for the affective component of pain.

Adolescent

Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: evidence for altered temporal summation of pain.

Temporomandibular disorders (TMD) represent a group of chronic painful conditions involving the muscles of mastication and the temporomandibular joint. Several studies have reported that TMD is associated with enhanced sensitivity to experimental pain. Twenty-three TMD subjects and 24 pain-free matched control subjects participated in a set of studies which were designed to evaluate whether the temporal integrative aspects of thermal pain perception are altered in TMD patients compared with control subjects. Specifically, we have examined in both TMD patients and in age- and gender-matched control subjects: (1) the time-course and magnitude of perceived pain evoked by the application of sustained 7-s noxious thermal stimuli (45-48 degrees C) to the face and forearm, (2) the central summation of C-fiber-mediated pain produced by applying brief trains of noxious heat pulses to the skin overlying the ventral aspect of the right palm and (3) the ability to discriminate small increments in noxious heat applied to facial and volar forearm skin. Data collected from these studies indicate that TMD patients show enhanced temporal integration of thermal pain compared with control subjects. TMD patients show greater thermal C-fiber-mediated temporal summation than pain-free subjects and they report a greater magnitude of sustained noxious heat pulses applied to either the face or the forearm than control subjects. In contrast to these findings, TMD and pain-free subjects are equally able to discriminate and detect small increments of heat applied to noxious adapting temperatures. These findings suggest that the augmented temporal integration of noxious stimuli may result from alterations in central nervous system processes which contribute to the enhanced pain sensitivity observed in TMD patients.

Adolescent

CSF, plasma viral load and HIV associated dementia.

Plasma viral burden has proven valuable in predicting the future course of systemic HIV related disease and the response to treatment. It is not known whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict onset of or response to treatment of nervous system disease. We propose a model of viral load mediated neurotoxicity underlying peripheral and central HIV associated neurological disease. The objective of this preliminary study was to assess the relationship of HIV associated neurological disease to quantitative viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both plasma and cell free (centrifuged) CSF. Subjects underwent concurrent comprehensive neurological and neuropsychological evaluations. In general, systemic viral load, as measured in plasma, was greater than that found in cell free CSF. Cell free CSF HIV RNA viral load was significantly correlated with neurological dysfunction, whereas plasma viral load was not. The sole subject with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD) on clinical examination.

AIDS Dementia Complex

Prognostic markers for colorectal cancer: expression of P53 and BCL2.

P53 is a tumor suppressor gene that has been implicated in the pathogenesis of a wide range of tumor types including colorectal cancers. bcl2 is a proto-oncogene that inhibits apoptosis. Immunostaining for P53 and BLC2 protein product was performed in a retrospective series of 80 colorectal carcinomas with a minimum follow-up of 5 years. The aim of the study was to evaluate the prognostic significance of P53 and BCL2 protein expression and their correlation with clinicopathologic variables such as pathologic disease stage (Dukes system), histologic grade, and vascular invasion. The patients were 41 to 76 years of age, and the follow-up ranged between 5 and 10 years. Among the 80 cases, 30 were Dukes stage A and 50 stage B. We found vascular invasion in 21.2%. P53 and BCL2 expression was detected, respectively, in 30.0% and 8.8%. We concluded that the P53 and BCL2 expression detected by immunohistochemistry in routinely processed, paraffin-embedded tissues: (1) has no prognostic significance; and (2) was not correlated with pathologic disease stage, histologic grade, or vascular invasion. Nevertheless, the number of patients in our study was small, and we believe that investigation of a larger series of patients is indicated.

Adult

Spontaneous development of plasmacytomas in a selected subline of BALB/cJ mice.

Sixty per cent of BALB/cAnPt mice injected intraperitoneally (i.p.) with tetramethylpentadecane (pristane) develop plasmacytomas (PCs), whereas less than 10% of BALB/cJ develop such tumours. Most other mouse strains are completely resistant. Resistance is dominant over susceptibility in F1 hybrids between BALB/cAnPt and the resistant non-BALB/c strains, suggesting that susceptibility may be due to some genetic defect. (BALB/cAnPtxBALB/cJ)F1 hybrids have a PC incidence of 36-42%. Previously, BALB/cJ has been shown to harbour at least one resistance gene (Potter et al., Genomics 1988, Vol. 2, pp. 257-262). On the assumption that BALB/cJ may contain a segregating resistance gene, we cross BALB/cJ females with pristane-pretreated BALB/cJ males that were found to be carrying PC cells intraperitoneally 5-7 months after pristane treatment. After two selective crosses, 62% of the BALB/cJ subline BALB/cM2/22 developed PC after pristane and 52% after pristane followed by Abelson virus, while unselected controls had an incidence of 11% and 0%, respectively. Moreover, six spontaneous plasmacytomas developed in untreated females of the selected colony. Five of these carried T(12; 15) (F2; D2/3) translocations. The sixth had a T(1; 10) (G; C1) translocation and an interstitial duplication of segment (C1/E3) on one chromosome 5. It may be concluded that pristane treatment is not a prerequisite for the induction of the PC associated Ig/myc translocations.

Animals

[The alcohol-dependent outpatient: a clinical typology].

The aim of this study was to construct a typology integrating sociodemographic, clinical and personality data of alcohol-dependent patients. We studied a consecutive population attending an alcohol-dependent outpatient psychiatric department, assessed by instruments that measured psychiatric, psychopathological, personality and sociodemographic characteristics of alcohol-dependent patients. The factorial analysis allowed us to define three main expressions of alcoholism: physical, psychological and social. In the elicited typology, both physical and social appear mixed in their expression. The psychological expression is divided into two main categories: the alexithymic (with a depressive personal and family history) and the psychopathologic type (with actual depression and anxiety). This typology should allow us to correlate these types with neurophysiological and biochemical patterns and could be particularly useful in building an etiologic model of alcohol dependence which could contribute to a better prediction of prognosis and choice of the best therapeutic intervention.

Adult

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Bipolar Disorder

Prostate-derived soluble factors block osteoblast differentiation in culture.

Bone metastasis is a common event and a major cause of morbidity in prostate cancer patients. After colonization of bone, prostate cells induce an osteoblastic reaction which is not associated with marrow fibrosis (i.e., osteoblast but not fibroblast proliferation). In the present study we test the hypothesis that the tumoral prostatic cell line (PC-3) secretes factors that block the osteoblast differentiation process, resulting in an increase of the relative size of the proliferative cell pool. Our results, using fetal rat calvaria cells in culture, show that conditioned medium from PC-3 cells (PC-3 CM) stimulates osteoblast proliferation and inhibits both alkaline phosphatase (AP) activity (an early differentiation marker) and the mineralization process, measured as calcium accumulation (late differentiation marker). The inhibition of the expression of AP and mineralization depends on the presence of PC-3 CM during the proliferative phase of culture and suggests that both processes occur in a nonsimultaneous fashion. The inhibitory effect of PC-3 CM was not reverted by dexamethasone, which would indicate that prostatic-derived factors and the glucocorticoid do not share a common site of action. Measurement of the proliferative capacity of subcultures from control and treated cells demonstrates that PC-3 CM treatment induces the maintenance of the proliferative potential that characterizes undifferentiated precursor cells.

Alkaline Phosphatase

Ig/myc translocations of the plasmacytoma-prone BALB/c strain occur independently of the genetic and parental origin of the affected chromosomes 6, 12, and 15.

Virtually all murine plasmacytomas (MPCs) carry chromosomal translocations that juxtapose myc on chromosome 15 (chr 15) to one of the three immunoglobulin loci carrying chr 6, 12, or 16. Only some mouse strains are susceptible to MPC induction, however, with BALB/c as the outstanding example. Most other strains are resistant. Our earlier studies with reciprocal BALB/c<-->DBA/2 chimeras suggested that part of this susceptibility is determined at the level of the target cell itself (DBA/2 is MPC resistant). The probability of the Ig/myc translocation is one of the possibly relevant variables. Because MPC resistance is dominant over susceptibility, it is conceivable that the translocations prevail due to some deficiency of the Ig rearrangement or Ig-associated repair mechanisms in BALB/c cells. This could be determined at the level of the chromosomes that participate in the translocation or by genes on other chromosomes. Here, we show that the substitution of the BALB/c-derived chr 12, 6, and 15, which carry IgH, kappa, and myc, respectively, with their homologs derived from MPC-resistant mice, did not affect MPC susceptibility. The use of Robertsonian 4.12 and 6.15 chromosomes in this study has also provided us with the opportunity to assess the parental derivation of the chromosomes participating in the translocation. In contrast to the human chronic myeloid leukemia (CML)-associated BCR/ABL fusion transcript, where a strong bias was claimed that was attributed to imprinting, we have found that the parental chromosomes were randomly involved in the translocation. We have also shown that the translocations could be of uniparental or biparental origin.

Animals

Soluble factors produced by PC-3 prostate cells decrease collagen content and mineralisation rate in fetal rat osteoblasts in culture.

Approximately 70% of patients with prostate cancer develop bone metastases in the advanced state of the disease. In the present study, we sought to test the hypothesis that prostatic cancer cells produce factors that inhibit the mineralisation process in vitro, decreasing the content of type I collagen in rat fetal calvaria osteoblasts. We investigated the capacity of conditioned media (CM) from the human prostatic tumour cell line PC-3 to inhibit the expression of the differentiation programme on osteoblasts in culture, with a primary focus on type I collagen synthesis and degradation. Our results show that PC-3 CM inhibits collagen synthesis and stimulates the production of interstitial collagenase from osteoblasts. A consequential decrease in the content of immunoreactive type I collagen was observed. We have previously demonstrated that PC-3 CM blocks osteoblast differentiation in culture. We propose that under the effect of factors present in PC-3 CM, osteoblastic cells retain the undifferentiated phenotype.

Animals

Genetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22-q23.

Manic depressive illness, or bipolar disorder (BP), is characterized by episodes of elevated mood (mania) and depression. We designed a multistage study in the genetically isolated population of the Central Valley of Costa Rica to identify genes that promote susceptibility to severe BP (termed BPI), and screened the genome ot two Costa Rican BPI pedigrees (McInnes et al., submitted). We considered only individuals who fulfilled very stringent diagnostic criteria for BPI to be affected. The strongest evidence for a BPI locus was observed in 18q22-q23. We tested 16 additional markers in this region and seven yielded peak lod scores over 1.0. These suggestive lod scores were obtained over a far greater chromosomal length (about 40 cM) than in any other genome region. This localization is supported by marker haplotypes shared by 23 of 26 BPI affected individuals studied. Additionally, marker allele frequencies over portions of this region are significantly different in the patient sample from those of the general Costa Rican population. Finally, we performed an analysis which made use of both the evidence for linkage and for association in 18q23, and we observed significant lod scores for two markers in this region.

Alleles

Follow-up of a human accidental infection by Leishmania (Viannia) braziliensis using conventional immunologic techniques and polymerase chain reaction.

The results of a two-year follow-up study of an accidental human infection with Leishmania (Viannia) braziliensis are presented. Western blots, indirect immunofluorescence, and intradermal reaction assays were not able to detect the infection before week 18 postinfection, whereas using the polymerase chain reaction (PCR) on blood samples, parasite DNA was detected at week 8. All test results, except the intradermal reaction followed the cure process and 12 weeks after the last chemotherapy injection (week 36 postinfection), all were negative. However, a year after cure, the PCR became positive again and has remained so for two years. To determine in which blood cell fraction the parasite was evident, enriched lymphocyte and monocyte fractions were assayed by the PCR. These results are discussed in the context of persistent infections.

Accidents

Trace element reference values in tissues from inhabitants of the European Union. IX. Harmonization of statistical treatment: blood cadmium in Italian subjects.

Obtaining reliable trace element reference values in tissues and fluids from inhabitants of the European Union relies on the availability of standardized and harmonized protocols for the statistical treatment of the data on trace element levels in general European populations. In this context, cadmium was measured in the blood (BCd) of 514 Italian inhabitants from the Lombardy region and the results statistically treated and presented according to a procedure which includes: simple descriptive statistics and graphical analysis such as stem and leaf and box-plot representations (average BCd levels were 0.62 microgram/l; geometric mean, 0.51 microgram/l; median, 0.50 microgram/l; mode, 0.30 microgram/l; 95th percentile, 1.48 micrograms/l; 5th percentile, 0.20 microgram/l); p-p plot, Shapiro-Wilk and Lilliefors tests for normality (the distribution of the data is closer to the log-normal distribution and inconsistent with the hypothesis of normality); analysis of variance (BCd increases from 20 to about 60 years and then decreases; it is influenced by smoking but not by body mass and alcohol consumption and it is higher in men than in women); and step wise multiple regression analysis (BCd is influenced by the number of cigarettes/day and the total dose of exposure, cigarettes/day multiplied by smoking years). Tentative reference intervals for BCd based on the log transformation of the data are 0.14-1.82 micrograms Cd/l (whole population); 0.16-1.94 micrograms Cd/l (male) and 0.13-1.66 micrograms Cd/l (female); 0.24-2.68 micrograms Cd/l (smokers); and 0.14-1.27 micrograms Cd/l (non-smokers).

Adult

Evaluation of satiety sensations and food intake after different preloads.

The reproducibility of three questions, related to fullness, satiety and desire to eat, rated on an unmarked triangle was verified. In four sessions 12 volunteers ate pasta with tomato sauce (520 kcal) and were asked to rate the sensations felt. There was no difference in rating scores of the replications so the proposed questionnaire provides a stable measure of sensations related to satiety. Subsequently three satiety conditions were studied. Two foods, one rich in carbohydrate, pasta (baked macaroni) and the other in protein, polpette (meatballs), were used as loads at two calorie levels and as preload before an "ad libitum" meal. All the three questions proved useful in discriminating between the different satiety conditions. The food intake underlines the specificity of satiety: subjects, after eating a preload which previously had satiated them, ate other foods in different amounts depending on the kind of preload eaten. Food intake was significantly higher after the pasta preload, furthermore "fullness" and "satiety" ratings were significantly highest after the meatball preload, suggesting that in our experimental conditions, meatballs were more satiating than pasta. In conclusion, this study highlights the validity of using several quite different questions to study hunger and satiety, together with the actual food intake.

Adult

Defective natural killer cell cytotoxic activity in feline immunodeficiency virus-infected cats.

Flow cytometry has been employed to study NK cell cytotoxic activity in cats infected with feline immunodeficiency virus. The results show that animals infected for 12 months or more have decreased levels of NK cell cytotoxic activity in their blood. The impairment could not be overcome by in vitro treatment of effector cells with interleukin 2. Additional results suggest that the NK cells of infected cats are defective, in that they are still able to bind to target cells but have a reduced ability to kill them.

Animals