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Biomedical subjects

C Franco

Publications and source records attributed to C Franco.

At least 19 recordsLinked to original sources

Assessing occupational exposure as risk for tuberculous infection at a teaching hospital in São Paulo, Brazil.

OBJECTIVE: To determine the risk for TB infection among nurses exposed to TB patients and non-exposed employees, and to evaluate associated aspects to initiate TB prevention in a teaching hospital in Brazil. DESIGN: A cross-sectional tuberculin skin test (TST) survey and assessment questionnaire of 169 nurses exposed to patients (exposed group [EG]) and 164 administrative employees (comparative group [CG]). RESULTS: The prevalence of positive TST was 59.7% in the EG and 53.7% in the CG (P = 0.26). Univariate analysis revealed, in the CG, association of TST positivity with BCG scar (P = 0.002), and, in the EG, with male sex (P = 0.02) and working at that hospital for >2 years (P < 0.001). On multivariate analysis, male sex (P = 0.0444), working at the institution for >2 years (P < 0.0001) and BCG scar (P = 0.0004) were associated with positive TST, while occupational exposure was not. CONCLUSIONS: The results suggest that all health care workers should be evaluated in an institutional TB prevention programme because community exposure to TB and BCG vaccination may have influenced TST positivity in the studied population.

Adult↗

A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree.

Generalized epilepsy with febrile seizures plus (GEFS+) is an inherited epileptic syndrome with a marked clinical and genetic heterogeneity. Here we report the molecular characterization of a large pedigree with a severe clinical form of GEFS+. Genetic linkage analysis implied the involvement of the FEB3 in the disease phenotype of this family (parametric two-point lod-score of 2.2). Sequencing of the SCN1A gene revealed a novel aspartic acid for glycine substitution at position 1742 of this sodium channel subunit. The amino-acid replacement lies in the pore-forming region of domain IV of SCN1A. Our observations are consistent with the genotype-phenotype correlation studies suggesting that mutations in the pore-forming loop of SCN1A can lead to a clinically more severe epileptic syndrome.

Adult↗

Mutation at position -132 in the islet amyloid polypeptide ( IAPP) gene promoter enhances basal transcriptional activity through a new CRE-like binding site.

AIMS/HYPOTHESIS: Mutations in the islet amyloid polypeptide ( IAPP) gene may play a potential role in the abnormal regulation or expression of the peptide. The aim of this study was to determine the functional role of the -132 G/A mutation reported in the promoter region of the IAPP gene in a population of Spanish Type 2 diabetic patients. METHODS: We investigated the transcriptional activity using MIN6 cells and luciferase reporter plasmids in several culture conditions. Key regulatory elements of the IAPP promoter region were also analysed by electrophoretic mobility shift assays (EMSA). RESULTS: The mutant construct doubled IAPP transcriptional activity ( p<0.001). Both constructs showed severely reduced promoter activity (four-fold decrease) in the presence of verapamil and diazoxide. In contrast, IAPP promoter activity was doubled after incubation with forskolin or dexamethasone, regardless of the glucose concentrations in the culture media. EMSA revealed that the -132 G/A mutation increased the binding affinity through two DNA-protein complexes. In addition, a cAMP-responsive element binding protein (CREB) was identified by super-shift EMSA. CONCLUSIONS/INTERPRETATION: Our studies show that the wild-type and the mutant constructs are regulated in a similar pattern under all conditions, strongly indicating that the -132 G/A mutation increases basal but not inducible transcription. These results may be explained by new binding to the mutant region through CREB and other transcription factors not yet identified.

Amino Acid Substitution↗

Pancreatic islets from cyclin-dependent kinase 4/R24C (Cdk4) knockin mice have significantly increased beta cell mass and are physiologically functional, indicating that Cdk4 is a potential target for pancreatic beta cell mass regeneration in Type 1 diabetes.

AIMS/HYPOTHESIS: Cyclin-dependent kinase 4 (Cdk4) is crucial for beta cell development. A mutation in the gene encoding for Cdk4, Cdk4R24C, causes this kinase to be insensitive to INK4 cell cycle inhibitors and induces beta cell hyperplasia in Cdk4R24C knockin mice. We aimed to determine whether this Cdk4R24C mutation also affects proper islet function, and whether it promotes proliferation in human islets lentivirally transduced with Cdk4R24C cDNA. METHODS: Our study was conducted on wild-type and Cdk4R24C knockin mice. Pancreases were morphometrically analysed. Intraperitoneal glucose tolerance tests and intravenous insulin tolerance tests were performed on wild-type and Cdk4R24C mice. We also did in vitro islet perifusion studies and islet metabolic labelling analysis. Human islets were transduced with Cdk4R24C cDNA. RESULTS: Pancreatic islets from Cdk4R24C knockin mice exhibit a larger insulin-producing beta cell area and a higher insulin content than islets from wild-type littermates. Insulin secretion in response to glucose is faster and reaches a higher peak in Cdk4R24C mice without leading to hypoglycaemia. Conversion of pro-insulin into insulin and its intermediates is similar in Cdk4R24C and wild-type mice. Glucose utilisation and oxidation measured per islet were similar in both experimental groups. Insulin secretion was faster and enhanced in Cdk4R24C islets perifused with 16.7 mmol/l glucose, with slower decay kinetics when glucose returned to 2.8 mmol/l. Moreover, human islets expressing Cdk4R24C cDNA exhibited higher beta cell proliferation. CONCLUSIONS/INTERPRETATION: Despite their hyperplastic growth, Cdk4R24C insulin-producing islet cells behave like differentiated beta cells with regard to insulin production, insulin secretion in response to glucose, and islet glucose metabolism. Therefore Cdk4 could possibly be used to engineer a source of beta cell mass for islet transplantation.

Animals↗

Anti human papillomavirus vaccine: the checkmate to human papillomavirus?

Cervical cancer is the second most frequently found neoplasia in women worldwide. At least 95% of cervical cancers contain viral DNA which, in 80% of cases, belongs to one of the human papillomavirus (HPV) viral types at high oncogenic risk: 16, 18, 31 and 45. HPV is, at this point, considered the first "necessary cause" of cervical cancer, against which primary prevention with a reduction in the risk of infection can be carried out. Numerous molecular biological studies have been conducted to identify the biological markers of this infection and to refine an effective and well tolerated vaccine capable of preventing HPV infection as well as possibly treating those cases in which the infection has already caused an HPV-related disease of the genital tract. In the near future, the real primary prevention of this disease will be conducted, similar to what occurred for Hepatitis B, using immunoprophylaxis with an anti-cancer vaccine.

Female↗

Unconverted chars obtained during biomass gasification on a pilot-scale gasifier as a source of activated carbon production.

Biomass gasification was used to produce activated carbon on a pilot-scale fluidised-bed gasifier. The feedstock included both biomass alone and biomass mixed with coal and coal/granulated plastic wastes. This paper reports the results obtained from four different runs undertaken under various conditions of fuel supply, different ratios of steam/air for the gasification and temperature. These conditions were selected because they led to a significant amount of unconverted chars produced during gasification (from 0.72 to 1.4 kg) which then served as raw material for the production of activated carbon whilst the amount of gas obtained was also high enough for its potential use for different end-use applications. From the analysis of the results obtained, it can be concluded that a reasonable porosity development (mainly in the area of narrow micropores) was obtained by gasifying unblended pine wastes with steam for 4 h, producing about 1.4 kg of good-quality activated carbon (micropore volume of 0.263 cm(3)/g). In other runs, chars with a reduced microporosity development (i.e. 0.180 cm(3)/g) were obtained, however, they could be used as a proper starting material for the chemically activated carbon production.

Bioelectric Energy Sources↗

Lymph node reticulum cell neoplasm with progression into cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma: a case study.

AIMS: To detail on sequential biopsies the morphological and immunohistochemical features of a case of primary lymph nodal fibroblastic reticulum cell (FBRC) tumour which progressed into a clinically aggressive cytokeratin-positive interstitial reticulum cell (CIRC) sarcoma. METHODS AND RESULTS: A 70-year-old female underwent surgical excision of an enlarged submandibular lymph node. The nodal architecture was effaced by a neoplastic proliferation of medium to large cells, round to oval to spindle in shape, growing in a storiform pattern. The tumour stained for vimentin, CD68, factor XIIIa, alpha1-antitrypsin, fascin and actin. Dendritic and endothelial cell markers were negative. A diagnosis of FBRC tumour was made by combining pathological and clinical data. The patient received no therapy but 5 months later the tumour relapsed, exhibiting a deceptively pleomorphic cytology, phenotypic changes (strong cytokeratin positivity), intense p53 expression and aggressive clinical course with fatal outcome. In-situ hybridization for Epstein-Barr virus was negative. CONCLUSIONS: We speculate that the morphological changes and p53 expression of the relapsing neoplasm might reflect tumour cell dedifferentiation, in keeping with the aggressive clinical course. The intense p53 expression suggests that this oncoprotein might also play a role in reticulum cell tumorigenesis.

Aged↗

Three-dimensional sonography and hysterosalpingosonography in the diagnosis of uterine anomalies.

Uterine anomalies implicated in female subfertility, implantation failure and miscarriages can often be detected often by two-dimensional transvaginal (2D TV) ultrasound scanning. When used as a screening test TV ultrasound has provided sensitivity rates of up to 100% about uterine anomalies. Improved depiction has been achieved with the development of hysterosalpingosonography (HSSG). The anechoic interface provided by the saline solution allows the examiner to determine whether an abnormality is intracavitary, endometrial, or submucosal. The aim of this study was to evaluate the role of 2D TV contrast sonography and 3D TV ultrasound in the diagnosis of congenital uterine anomalies in comparison with their appearance of hysterosalpingosonography findings.

Adolescent↗

Polymorphism in intron 2 of islet amyloid polypeptide gene is associated with lower low-density lipoprotein cholesterol in nondiabetic subjects and in type 2 diabetic patients.

The aim of this study was to investigate the presence of mutations in the islet amyloid polypeptide (IAPP) gene in a Spanish population with type 2 diabetes and gestational diabetes mellitus (GDM). Using polymerase chain reaction single-stranded conformation polymorphism, we examined the coding region and the 5'-untranslated region (UTR) of the IAPP gene in 177 unrelated type 2 diabetic patients, 110 healthy control subjects, 38 women with GDM, and 38 gestational control subjects. Mutations were confirmed by DNA sequencing. A heterozygous C-to-A nucleotide substitution at +79 bp in intron 2 of the IAPP gene was detected. The frequencies of the +79-bp polymorphism (A allele) were 6.8% in type 2 diabetic patients, 7.7% in nondiabetic control subjects, 11.8% in women with GDM, and 9.2% in gestational control subjects. No AA genotypes were detected. Nondiabetic subjects and patients with type 2 diabetes bearing the CA genotype had lower low-density lipoprotein (LDL) cholesterol levels than subjects bearing wild genotype. Multivariate logistic regression analysis showed an independent association (p < 0.001; odds ratio: 0.33; 95% confidence interval: 0.17-0.63). We did not detect any sequence variant within exons 1 or 2. One diabetic patient was heterozygous for a silent mutation at codon 31 of exon 3 (Asn31 AAC --> AAT). Our findings indicate that the presence of the +79-bp polymorphism of the IAPP gene in nondiabetic subjects and in patients with type 2 diabetes is associated with lower levels of LDL cholesterol. Furthermore, abnormalities of the coding regions or the 5'-UTR of the IAPP gene are not associated with type 2 diabetes or GDM in the Spanish population.

Aged↗

Eotaxin and CCR3 are up-regulated in exacerbations of chronic bronchitis.

BACKGROUND: Eosinophils and T lymphocytes represent constant features in the airways of subjects with exacerbated chronic bronchitis. Eotaxin is the most potent and selective eosinophil chemoattractant which can also attracts lymphocytes. The aim of the study was to evaluate the expression of eotaxin and its receptor, CCR3, in bronchial airways during exacerbation of chronic bronchitis. METHODS: By immunohistochemistry we studied eotaxin and CCR3 expression in the lamina propria of 14 subjects with acute exacerbation of chronic bronchitis. 20 asthmatics, and 8 healthy subjects. We determined the cell types expressing the CCR3 receptor by colocalization experiments. We finally studied the relationship between eotaxin and CCR3 and eosinophils and T lymphocytes. RESULTS: The number of eotaxin+ and CCR3+ cells was significantly higher in exacerbated chronic bronchitis (P<0.003 and P<0.002) and asthma (P<0.002 and P<0.0001) when compared to healthy subjects. CCR3 was mainly expressed by eosinophils and to a lesser extent by CD4+ and CD8+ lymphocytes. In exacerbated chronic bronchitis the number of CCR3+ cells was strongly correlated to the number of eosinophils (P<0.0002. r=0.85) and to the number of CD4+ lymphocytes (P<0.05, r=0.57). CONCLUSION: Our study suggests that eotaxin and CCR3 are up-regulated and could be involved in the eosinophil and CD4+ lymphocyte recruitment into the airways which occur during acute exacerbations of chronic bronchitis.

Adult↗

Reproductive outcome after laparoscopic treatment of endometriosis.

PURPOSE OF INVESTIGATION: To evaluate the pregnancy rate after laparoscopic treatment of endometriosis. PATIENTS AND METHODS: 47 infertile women undergoing laparoscopic treatment of endometriosis. RESULTS: rAFS stage was as follows: 11% of patients had Stage I, 11% Stage II, 53.3% Stage III and 24.4% Stage IV. The mean duration of follow-up was 48.5 +/- 18.44 months. The overall pregnancy rate was 64.4%. Eighteen out of 26 women (69%) became pregnant within six months after laparoscopy, 23% at 12 months, 11% within 24 months, and 11% after two years (p < 0.01). Adnexal adhesions and tubal status significantly affected the pregnancy rate. No differences were found regarding the stage of disease and the presence of ovarian endometriomas. CONCLUSION: Laparoscopic treatment of endometriosis enhances fertility and the pregnancy rate is highest within the first six months after surgery. Adnexal adhesions and tubal conditions influence the reproductive outcome.

Adult↗

Visceral obesity and the role of the somatotropic axis in the development of metabolic complications.

It is well recognized that aberrant fat localization such as visceral obesity rather than total body fat mass is a major risk factor for cardiovascular disease and type 2 diabetes mellitus. During recent decades, several studies have described a range of metabolic disturbances associated with abdominal obesity, including glucose intolerance, hyperinsulinaemia, insulin resistance, hypertension and dyslipoproteinaemia, now widely known as the metabolic syndrome. Several abnormalities in the hypothalamic-pituitary axis have been described associated with visceral obesity, suggesting a central neuroendocrine dysregulation including increased cortisol concentration and impaired gonadotropin and growth hormone (GH) secretion. Some steps in the chain of events in this theory still remain unclear, however, although these findings have introduced new therapeutic possibilities. These include therapy with sex steroids in both viscerally obese men and women, and several attempts to use GH to treat the endocrine abnormalities present in visceral obesity. The results of these studies are promising, but the therapies are still not recommended for general use.

Abdomen↗

Molecular typing by pulsed-field gel electrophoresis of Spanish animal and human Listeria monocytogenes isolates.

A total of 153 strains of Listeria monocytogenes isolated from different sources (72 from sheep, 12 from cattle, 18 from feedstuffs, and 51 from humans) in Spain from 1989 to 2000 were characterized by pulsed-field gel electrophoresis. The strains of L. monocytogenes displayed 55 pulsotypes. The 84 animal, 51 human, and 18 feedstuff strains displayed 31, 29, and 7 different pulsotypes, respectively, indicating a great genetic diversity among the Spanish L. monocytogenes isolates studied. L. monocytogenes isolates from clinical samples and feedstuffs consumed by the diseased animals were analyzed in 21 flocks. In most cases, clinical strains from different animals of the same flock had identical pulsotypes, confirming the existence of a listeriosis outbreak. L. monocytogenes strains with pulsotypes identical to those of clinical strains were isolated from silage, potatoes, and maize stalks. This is the first study wherein potatoes and maize stalks are epidemiologically linked with clinical listeriosis.

Animal Feed↗

Population genetic implications from sequence variation in four Y chromosome genes.

Some insight into human evolution has been gained from the sequencing of four Y chromosome genes. Primary genomic sequencing determined gene SMCY to be composed of 27 exons that comprise 4,620 bp of coding sequence. The unfinished sequencing of the 5' portion of gene UTY1 was completed by primer walking, and a total of 20 exons were found. By using denaturing HPLC, these two genes, as well as DBY and DFFRY, were screened for polymorphic sites in 53-72 representatives of the five continents. A total of 98 variants were found, yielding nucleotide diversity estimates of 2.45 x 10(-5), 5. 07 x 10(-5), and 8.54 x 10(-5) for the coding regions of SMCY, DFFRY, and UTY1, respectively, with no variant having been observed in DBY. In agreement with most autosomal genes, diversity estimates for the noncoding regions were about 2- to 3-fold higher and ranged from 9. 16 x 10(-5) to 14.2 x 10(-5) for the four genes. Analysis of the frequencies of derived alleles for all four genes showed that they more closely fit the expectation of a Luria-Delbrück distribution than a distribution expected under a constant population size model, providing evidence for exponential population growth. Pairwise nucleotide mismatch distributions date the occurrence of population expansion to approximately 28,000 years ago. This estimate is in accord with the spread of Aurignacian technology and the disappearance of the Neanderthals.

Aged↗

Chemiluminescence detection of nine corticosteroids in liver.

A method for the determination of nine corticosteroids in bovine liver was developed. The liquid-liquid extraction method consisted in the addition of sodium hydroxide to the tissue sample followed by extraction with ethyl acetate. After centrifugation, the extract was evaporated to dryness and the residue redissolved in acetonitrile. The removal of fats was performed with n-hexane and the acetonitrile layer was evaporated. Afterwards, analysis of the extracts was performed using high-performance liquid chromatography with chemiluminescence detection employing luminol as reagent. The recovery curves, performed at five spiking levels (different for each corticosteroid), showed that recoveries of at least 70.5% could be obtained from liver. The chemiluminescence detection gave satisfactory results with respect to sensitivity, and the LOQ ranged from 0.13 ppb for prednisolone to 8.40 ppb for betamethasone. The maximum mean RSD was 4.8% and 7.3% for intra- and inter-day assay, respectively.

Animals↗

[Ovulation induction and the risk of ovarian tumors].

In the last years it has been observed a more and more increasing number of women submitted to therapies for induction of ovulation (disorders of the ovulation represent 33% of the causes of female infertility). In 1998, these therapies had been administrated to approximately two million of USA women. Various Authors have assumed a possible relationship between induction of ovulation and ovarian tumors. Between 1982 and 1997, at least 43 cases of ovarian tumors have been published (among these, there were also 25 cases of epithelial tumors) occurring in women previously treated with ovulation induction. The mean age of patient was 30.3 years, approximately 20 years younger than normal patient population for the same tumors. Among the possible causes of epithelial ovarian tumors, there is the trauma of the ovary surface caused by the continuous repeating of the ovulation phenomenon (incessant ovulation). Gynecologist should be aware of this potential risk for their patients. Multicentric studies should be evaluated in order to establish the risk of ovarian cancer in women treated for infertility problems. A survey of the international literature is made in order to analyse the epidemiological studies and to discuss the relationship between ovulation inducing agents and ovarian tumors.

Adult↗