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Biomedical subjects

A Botta

Publications and source records attributed to A Botta.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sonographic findings in type I glycogen storage disease.

PURPOSE: The aim of this study was to document the sonographic appearance and dimensions of the liver and spleen in patients affected by type I glycogen storage disease and to correlate those findings with laboratory data to evaluate the potential role of sonography in diagnosing that disease. METHODS: Fourteen patients (age range, 3-26 years; 10 patients younger than 18 years) with type I glycogen storage disease proved by liver biopsy were studied prospectively with gray-scale sonography, color Doppler sonography, and spectral analysis. The liver, kidneys, spleen, portal system, hepatic veins, and hepatic arteries were evaluated. Laboratory data were correlated with sonographic findings. RESULTS: In 13 (93%), of 14 patients, the liver was enlarged, and in 11 patients (79%), hepatic echogenicity was increased. In 9 patients (64%), both kidneys were enlarged, and in 6 cases (43%), the spleen was enlarged. In all patients, flow in the portal, splenic, and superior mesenteric veins was hepatopetal, and flow in the hepatic veins was triphasic. In 5 patients (36%), both triglyceride and total cholesterol levels were higher than normal. No focal hepatic lesions were identified. Analysis found no significant association between sonographic findings and laboratory data. CONCLUSIONS: The most frequent sonographic findings in patients with type I glycogen storage disease were hepatomegaly, increased hepatic echogenicity, and enlarged kidneys. Sonography may help in the diagnosis of type I glycogen storage disease, but a liver biopsy is required for a definitive diagnosis.

Adolescent↗
PubMed2001

Pediatric heart transplantation: improving results in high-risk patients.

OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

ABO Blood-Group System↗
PubMed2001

Cloning and molecular characterization of three ubiquitin fusion degradation 1 (Ufd1) ortholog genes from Xenopus laevis, Gallus gallus and Drosophila melanogaster.

The yeast ubiquitin fusion degradation 1 (Ufd1) protein is involved in a degradation pathway for ubiquitin fused products. The human ortholog gene (UFD1-like, UFD1L) is deleted in patients affected by the DiGeorge/velocardiofacial syndromes. We report the cloning of UFD1L orthologs from Drosophila melanogaster (dufd1l), Xenopus laevis and Gallus gallus. The 1,125-bp Drosophila cDNA encodes a protein of 316 amino acids, showing 60% identity with the human and murine proteins. The identity to the G. gallus, X. laevis, C. elegans and S. cerevisiae proteins is 95%, 83%, 32%, and 36%, respectively. Northern expression data in Drosophila indicate that dufd1l is expressed through embryonic, larval and pupal development, as well as in the adult fly.

Adaptor Proteins, Vesicular Transport↗
PubMed2000

Naturally occurring woodchuck hepatitis virus (WHV) deletion mutants in chronically WHV-infected woodchucks.

Deletion mutants of hepatitis B virus (HBV) are often found in chronically HBV-infected patients. It has not been possible to study the significance of such deletion mutants on liver diseases in a suitable animal model. In this study, we characterized naturally occurring deletion mutants of woodchuck hepatitis virus (WHV) in 11 chronically WHV-infected woodchucks. Deletions within the WHV preS region (nt 2992-338) had a length of 72 or 84 bp and were located in the amino terminal part of preS1. Internal deletions within the core gene (CID) had variable lengths (103 to 312 bp) and were identified within the center of this gene (nt 2021-2587). Four of seven CIDs were in-frame deletions, whereas the remaining three CIDs were out-of-frame deletions and led to the interruption of the reading frame. Sequence analysis of cloned PCR products of CIDs showed that heterogeneous WHV deletion mutants coexisted in single woodchucks. In addition, WHV genomes with double deletions in the preS1 and the core region could be found. We were unable to detect the expression of truncated core proteins in transfection experiments. The CID mutations led to a marked increase of the expression of the luciferase gene which was fused to the start codon of WHV polymerase, probably due to the shortening of the untranslated region or the removal of AUGs preceding the polymerase start codon. The characterization of naturally occurring WHV deletion mutants will allow us to study their biological and pathogenic properties in the woodchuck model in the future.

Animals↗
PubMed2000

Evaluation of micronucleated lymphocytes, constitutional karyotypes and anti-p53 antibodies in 21 children with various malignancies.

The implication of environmental carcinogens in childhood cancer is still unknown. To assess a possible link between DNA damage and alterations of the tumor suppressor gene p53, blood samples of 21 children with malignancies were examined for the presence of micronuclei in lymphocytes using the cytokinesis blocked micronucleus assay (CBMA). The constitutional karyotypes were analyzed for chromosome abnormalities and the presence of anti-p53 antibodies in blood sera was evaluated by an enzyme-linked immuno sorbent assay (ELISA). A control group of 20 children was also included. The rates of micronucleated cells were 5.1 per thousand+/-3.9 and 2.4 per thousand+/-2.3 for the cancer and control groups, respectively. The difference between the groups were statistically significant (P<0.05 by the Mann-Withney rank sum test). Two children in the cancer group showed extensive chromosome breakage in lymphocytes. The sera of two other children from the cancer group and of one child from the control group contained anti-p53 antibodies. Chromosome breakage and anti-p53 antibodies from the five children were associated with increased micronucleated cell rates. The results of the present study suggest that genotoxic events can occur in the lymphocytes of children with a cancerous state.

Adolescent↗
PubMed1999

Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome.

The HPC-1/syntaxin 1A (STX1A) gene maps to the Williams syndrome (WS) commonly deleted region on chromosome 7q11.23 and encodes a protein implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. To assess the potential role of STX1A in the WS phenotype, we carried out expression studies at the RNA and protein levels, in fetal and adult human tissues. RNA in situ hybridization on human embryo sections showed strong STX1A expression in spinal cord and ganglia. However, in adulthood, this gene was preferentially expressed in brain, as shown by Northern blot and RT-PCR experiments. Marked expression levels were observed in cerebellum and cerebral cortex. The STX1A protein was prevalently distributed in the molecular layer of the cerebellar cortex. A qualitative and quantitative analysis using a specific anti-STX1A antibody did not disclose any significant difference among frontal, temporal, and occipital poles of the human adult cortex in the two hemispheres. This is the first study focused on STX1A expression in humans. Our results indicate that this gene is strongly expressed in cerebral areas involved in cognitive process, supporting a likely role in the neurological symptoms of WS.

Antigens, Surface↗
PubMed1999

Fatal poisoning due to intravasation after oral administration of barium sulfate for contrast radiography.

A fatal poisoning after oral administration of barium sulfate for contrast radiography is reported. Barium sulfate is an insoluble salt and therefore is almost nontoxic. The case described here involves a 61-year-old woman who underwent two CT scans of the digestive tract with oral administration of barium sulfate during a surgical procedure. Within several hours after the first barium swallow examination the patient presented nonspecific neurologic and cardiovascular manifestations that rapidly progressed and led to death a few days later. Laboratory findings demonstrated elevated levels of barium in the blood and cerebrospinal fluid. The most likely mechanism of poisoning was progressive intravasation of barium due to stasis of contrast material related to intestinal obstruction.

Acute Disease↗
PubMed1999

Congenital heart disease in mice deficient for the DiGeorge syndrome region.

The heterozygous chromosome deletion within the band 22q11 (del22q11) is an important cause of congenital cardiovascular defects. It is the genetic basis of DiGeorge syndrome and causes the most common deletion syndrome in humans. Because the deleted region is largely conserved in the mouse, we were able to engineer a chromosome deletion (Df1) spanning a segment of the murine region homologous to the human deleted region. Here we describe heterozygously deleted (Df1/+) mice with cardiovascular abnormalities of the same type as those associated with del22q11; we have traced the embryological origin of these abnormalities to defective development of the fourth pharyngeal arch arteries. Genetic complementation of the deletion using a chromosome duplicated for the Df1 DNA segment corrects the heart defects, indicating that they are caused by reduced dosage of genes located within Df1. The Df1/+ mouse model reveals the pathogenic basis of the most clinically severe aspect of DiGeorge syndrome and uncovers a new mechanism leading to aortic arch abnormalities. These mutants represent a mouse model of a human deletion syndrome generated by chromosome engineering.

Adaptor Proteins, Vesicular Transport↗
PubMed1999

Micronucleated lymphocyte rates from head-and-neck cancer patients.

We investigated whether head-and-neck cancers are associated with an increased micronucleated cell rates (MN cell rates) and whether risk factors for these cancers are associated with alterations in micronucleated lymphocytes. MN cell rates were assessed in cytokinesis-blocked lymphocytes of 57 head-and-neck cancer patients (CP) before any anticancer treatment and of 198 male and female healthy subjects (HS). In the HS group, only smoking status significantly affect MN cell rates. In CP group age, sex, tobacco status, alcohol status, tumor stage, family history of cancer had no significant effect. For the non-smokers, the comparison between MN cell rates in HS and CP adjusted for age and sex showed a significant difference. The increase of MN cell rates in non-smokers patients may be attributable to cancer status. For the smokers, the comparison of MN cell rates in HS and CP matched for age and sex showed no significant difference. Pathological status could mask the smoking effect on peripheral blood lymphocytes in patients. Moreover, it probably could partly explain why MN cell rates in matched-CP smokers and HS smokers were similar. The authors do not recommend the CBMN assay in this present form to study smoking DNA-damage effects in peripheral blood lymphocytes of cancer patients, especially for patients with upper aero-digestive tract cancers or lung cancers for which tobacco is the major risk factor.

Adult↗
PubMed1999

Evaluation of the genotoxic activity of paclitaxel by the in vitro micronucleus test in combination with fluorescent in situ hybridization of a DNA centromeric probe and the alkaline single cell gel electrophoresis technique (comet assay) in human T-lymphocytes.

Paclitaxel is a recent chemotherapeutic agent that inhibits tubulin depolymerization in tumoral cells. Despite its increasing use against various human cancers, the genotoxicity of paclitaxel has never been studied on normal human cells. The in vitro genotoxic effects of the drug were evaluated with two complementary mutagenesis tests on human T-lymphocytes: (1) the cytokinesis-blocked micronuclei assay (CBMN) in combination with fluorescent in situ hybridization (FISH) of nonspecific centromeric probes and (2) the comet assay performed in three ways: on stimulated lymphocytes as in the CBMN, and on freshly isolated lymphocytes at both 4 and 37 degrees C. A slight cytotoxicity of 2.5 to 10 nM paclitaxel was found in the CBMN and a significant increase in the binucleated micronucleated cell rates was observed, with a concentration-dependent manner. In the FISH analysis, more than 85% of the micronuclei (MN) were centromere positive, and a ratio of 72. 2 to 78.6% of these MN contained more than one centromere. Moreover, at 10 nM of paclitaxel, 35.6% of the cells are multimicronucleated lymphocytes. Unexpectedly, paclitaxel induced single-strand breaks on proliferating lymphocytes at 5 and 7.5 nM but not in resting cells, even at 5 to 15 microM. These in vitro results showed that (1) paclitaxel does not present any direct DNA action in resting cells, (2) DNA damage detected in stimulated lymphocytes may be linked either to a high frequency of cells in the S-phase cell cycle or to a direct DNA damaging effect on replicating cells, and (3) paclitaxel is a strong in vitro aneugenic drug on human normal cells, at clinically relevant concentrations.

Adult↗
PubMed1999

Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1.

Psoriasis is a chronic inflammatory dermatitis, affecting approximately 2% of the population. Major clinical features include red, scaly patches on scalp, elbows, and knees, with or without severe arthritis. Several putative susceptibility loci have been mapped by parametric and non-parametric linkage analysis to chromosome regions 2p, 4q, 6p, 8q, 16q, 17q, and 20p; however, the most significant results and confirmation of linkage are only available for the 17q and 6p chromosome regions at present. In this study, 22 multiplex Italian families were investigated for linkage to 6p and 17q susceptibility regions, using a set of four microsatellites. These analyses failed to detect significant linkage with any of the examined markers. A genome-wide scan was then performed on one of the largest pedigrees, searching for an additional susceptibility locus. This study disclosed a putative linkage to chromosome 1cen-q21 markers. When these microsatellites were analyzed in the remaining families of the sample, a significant linkage was observed using both parametric and non-parametric methods. The highest two-point lod score value was obtained with D1S305 marker (3.75 at 0 = 0.05). Non-parametric analysis at this locus also demonstrated a significant excess of allele sharing (p = 0.0001).

Chromosome Mapping↗
PubMed1999

Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes.

We present two patients with the full Williams syndrome (WS) phenotype carrying a smaller deletion than typically observed. The deleted region spans from the elastin gene to marker D7S1870. This observation narrows the minimal region of deletion in WS and suggests that the syntaxin 1A and frizzled genes are not responsible for the major features of this developmental disorder and provides important insight into understanding the genotype-phenotype correlation in WS.

Antigens, Surface↗
PubMed1998

A novel frameshift mutation 840delA and a novel polymorphism D203A in the steroidogenic acute regulatory protein gene in a Japanese patient with congenital lipoid adrenal hyperplasia. Mutations in brief no. 117. Online.

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomalrecessive disorder characterized by impaired production of all steroids including glucocorticoids, mineralocorticoids and sexsteriods. It has recently been reported that mutations in the steriodogenic acute regulatory protein (StAR) gene cause CLAH. We analyzed the StAR gene in a Japanese patient with CLAH. The patient was revealed to be a compound heterozygote bearing a nonsense mutation Q258X, changing codon 258 (CAG) encoding Gln to the stop codon TAG, and a novel framshift mutation 840delA resulting from deletion of one of the three adenosines normally present in codon 238 (AAA), thus leading to a frameshift after codon 237 (Thr) in the StAR gene. The patient was also revealed to be homozygous for a novel missense point mutation D203A, changing codon 203 (GAC) encoding Asp to GCC encoding Ala in the StAR gene. To elucidate the significance of the D203A mutation, we analyzed the StAR gene sequence in twenty normal subjects, and found that all of them were homozygous for the D203A mutation, indicating that the D203A mutation is an innocent polymorphism. In conclusion, we have identified a novel frameshift mutation 840delA which seems to cause 840delA and the first polymorphism D203A in the human StAR gene.

Adrenal Hyperplasia, Congenital↗
PubMed1998

[Splenomegaly and hypersplenism in cirrhotic patients before and after orthotopic liver transplantation].

PURPOSE: To measure the spleen length in patients with cirrhosis and portal hypertension with US and compare the measurements before and after orthotopic liver transplantation. To correlate splenic measures with laboratory data and Doppler flowmetry (mean portal vein flow velocity). MATERIALS AND METHODS: May, 1993, to January, 1997, fifteen patients with cirrhosis, portal hypertension and splenomegaly were examined and underwent orthotopic liver transplantation. The spleen length was measured before and after transplantation in 15/15 patients and it was also measured twice after transplantation in 10/15 patients. The mean portal venous flow velocity was measured before and after transplantation in 10/15 patients. The results were analyzed using the Student's t-test for paired and unpaired data; the association between the variables was evaluated by linear regression analysis; two-tailed p values were used. RESULTS: At the first control after orthotopic liver transplantation (mean time from transplantation 5.5 +/- 2.6 months; range 2.5-12.5 months) a significant decrease was found in spleen length (179 +/- 32 to 149 +/- 30 mm, p = .0001; mean percent decrease = 16.7 +/- 9.9%), hypersplenism disappeared in 9/13 cases, mean portal venous flow velocity, measured in 10/15 patients, showed an increasing trend (16.0 +/- 9.0 to 22.3 +/- 9.0 cm/s). At the first control the correlation between the values of mean portal flow velocity measured before and after transplantation was not significant (r = .558, p = .0939); the same was true for the correlation between mean portal flow velocity and spleen length. The second measurement of the spleen length after transplantation (mean time from the first follow-up 18.1 +/- 7.8 months; range 6.4-32.8 months) in 10/15 subjects demonstrated no significant changes in the spleen dimensions relative to the first examination (139 +/- 24 mm to 138 +/- 26 mm), and in 1/10 case hypersplenism disappeared. CONCLUSIONS: The measurement of the spleen length is proposed for the follow-up of the patients with cirrhosis and hypersplenism before and after orthotopic liver transplantation. In our study, the mean decrease in spleen length was 17% in the period from transplantation to the first US examination. In the patients who underwent a second measurement after transplantation no significant change in spleen length was observed.

Adult↗
PubMed1998

[Importance of micronucleus tests in cultured binuclear T lymphocytes for the detection of genotoxic events in cancer patients].

The cytokinesis-blocked micronucleus assay (CBMN) is a short-term mutagenesis test which offers an easier and less tedious alternative to metaphase chromosome analysis, with the advantage that exposure to both clastogens and aneugens may be detected. The CBMN assay has been used in evaluating the genotoxic consequences of exposures to environmental and occupational mutagens and carcinogens. Micronucleated cell rates (MN cell rates) were assessed in cytokinesis-blocked lymphocytes of 70 male and female cancer patients prior to any anticancer treatment. The study of interindividual variation factors showed that only age significantly affect MN cell rate, whereas sex, tobacco, alcohol, imaging techniques and tumour stage had no significant effect. The comparison of micronucleated cell rates in 198 healthy subjects and 70 cancer patients matched for age and sex showed a statistically significant difference. Spontaneous elevated MN cell rates of cancer patients refer to previous exposition of genotoxic or mutagenic environmental agents. Moreover, the MN cell rates in cancer patients most probably refers to various cellular lesions and genetic damages.

Adult↗
PubMed1997

Comparative mapping of the DiGeorge syndrome region in mouse shows inconsistent gene order and differential degree of gene conservation.

We have constructed a comparative map in mouse of the critical region of human 22q11 deleted in DiGeorge (DGS) and Velocardiofacial (VCFS) syndromes. The map includes 11 genes potentially haploinsufficient in these deletion syndromes. We have localized all the conserved genes to mouse Chromosome (Chr) 16, bands B1-B3. The determination of gene order shows the presence of two regions (distal and proximal), containing two groups of conserved genes. The gene order in the two regions is not completely conserved; only in the proximal group is the gene order identical to human. In the distal group the gene order is inverted. These two regions are separated by a DNA segment containing at least one gene which, in the human DGS region, is the most proximal of the known deleted genes. In addition, the gene order within the distal group of genes is inverted relative to the human gene order. Furthermore, a clathrin heavy chain-like gene was not found in the mouse genome by DNA hybridization, indicating that there is an inconsistent level of gene conservation in the region. These and other independent data obtained in our laboratory clearly show a complex evolutionary history of the DGS-VCFS region. Our data provide a framework for the development of a mouse model for the 22q11 deletion with chromosome engineering technologies.

Animals↗