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Biomedical subjects

A Bosch

Publications and source records attributed to A Bosch.

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

Human enteric viruses in Coquina clams associated with a large hepatitis A outbreak.

An outbreak of hepatitis A, affecting 183 people, occurred in Valencia (Spain). Epidemiological evidence pointed to an association of the outbreak with consumption of Coquina clams (Donax sp), imported frozen from Peru. Shellfish were analysed for the presence of hepatitis A virus (HAV), enteroviruses, rotaviruses, astroviruses, caliciviruses and hepatitis E virus. HAV was detected in 75% of assayed shellfish samples. Other enteric viruses were occasionally found in the same samples. Molecular epidemiological analysis of fragments of the VP1/2A and the 5' end of the genome from shellfish and sera isolates, revealed the presence of six variants belonging to a single genotype.

DNA, Viral↗
PubMed2001

Astrovirus detection in wastewater samples.

Procedures for the detection of astroviruses in wastewater samples have been developed and evaluated. Following these methodologies, we investigated the occurrence of astroviruses in wastewater samples from three different sewage treatments plants located in Southern France and two in the Barcelona area. Some positive samples were genotyped by analysis of a fragment of the ORF1a by restriction fragment length polymorphism (RFLP) with endonuclease DdeI. The amplimers generated contain several sites for the DdeI restriction endonuclease, being the number and location of sites different between strains.

DNA, Viral↗
PubMed2000

[Norwalk virus-like food poisoning after eating oysters].

BACKGROUND: The aim of this study was to conduct a clinical-epidemiological and microbiological investigation into an outbreak of food-borne disease due to the consumption of oysters. PATIENTS AND METHODS: A historic cohort study was conducted into the consumption of 15 food items and clinical symptoms. The influence of each foodstuff was assessed by Mantel-Haenzel stratified relative risk (RRM-H) at 95% confidence intervals, and was confirmed by dose-response analysis with a chi 2 test tendency. We investigated sample stools from 5 patients and 2 food-handlers. RESULTS: The overall attack rate was 38.0% (19/50). The median period of incubation was 39.0 h (maxim 62 and minimum 3 h). The symptoms were: fever 17.6% (3/17), diarrhoea 57.9% (11/19), vomits 84.2% (16/19), nausea 89.5% (17/19) and abdominal pain 89.5% (17/19). In stratified analysis, the Mantel-Haenzel method revealed a statistically risk for oysters (RRM-H = 3.3; IC 95%: 1.1-8.7), while the RRM-H value for sea snails was not significant (RRM-H = 2.8; IC 95%: 0.9-41.1). For oyster consumption, the dose-response test was statistically significant (p = 0.005). Examination by electron microscopy revealed small round structured viruses compatible with Norwalk-like virus. The oyster contamination was reported to the public health authority. CONCLUSIONS: This research highlights the usefulness of dose-response analysis in presenting epidemiological evidence, reveals the potential role of oyster consumption in food-borne disease such us Norwalk-like virus and show the need for monitoring production centres and oyster beds in order to prevent further cases of contamination.

Adult↗
PubMed2000

Reversal of pathology in the entire brain of mucopolysaccharidosis type VII mice after lentivirus-mediated gene transfer.

Gene transfer vectors derived from human immunodeficiency virus (HIV-1) efficiently transduce nondividing cells and remain stably integrated in their genome. Long-term expression of reporter genes has been documented after intracerebral injection of these vectors. Using a HIV-based vector, we looked for a reversal of brain damage in the beta-glucuronidase-deficient mucopolysaccharidosis type VII mouse, an animal model of human lysosomal storage diseases. The vector suspension was injected stereotactically in the brain of 10-week-old animals, an age at which storage lesions are patent in glia, perivascular cells, and neurons. Either a single intrastriatal injection or multiple injections in both cerebral hemispheres and in the cerebellum were performed. Local tolerance, enzyme delivery, and correction of storage lesions were investigated by comprehensive analysis of serial sections of the entire brain of mice killed 6 or 16 weeks postinjection. Histochemical staining detected enzyme activity in widely distributed areas, the size of which increased with time. Clearance of lysosomal storage extended far beyond enzyme-positive areas. In mice receiving multiple injections of the vector, complete correction or significant reduction of the pathology was observed in every section, suggesting disease regression in the entire brain. These results may have implications for the treatment of neurological symptoms in lysosomal storage diseases.

Animals↗
PubMed2000

Improvement of erythropoiesis in beta-thalassemic mice by continuous erythropoietin delivery from muscle.

beta-Thalassemias are highly prevalent genetic disorders that can cause severe hemolytic anemia. The main pathophysiologic feature of beta-thalassemia is the accumulation of unpaired alpha-globin chains in erythrocyte precursors and red blood cells (RBCs). This accumulation alters cell membrane function and results in early cell destruction and ineffective erythropoiesis. Correction of globin chain imbalance through the induction of fetal hemoglobin (HbF) synthesis is a tentative therapeutic approach for this class of diseases. In short-term in vitro or in vivo assays, recombinant human erythropoietin increases the frequency of erythroid precursors programmed to HbF in humans and to beta-minor globin in mice. In contrast, long-term treatment of beta-thalassemic patients did not induce HbF significantly. We took advantage of highly efficient adeno-associated virus-mediated (AAV-mediated) gene transfer into mouse muscle to induce a robust and sustained secretion of mouse erythropoietin in beta-thalassemic mice, which represent a suitable model for human beta-thalassemia intermedia. A 1-year follow-up of 12 treated animals showed a stable correction of anemia associated with improved RBC morphology, increased beta-minor globin synthesis, and decreased amounts of alpha-globin chains bound to erythrocyte membranes. More effective erythropoiesis probably accounted for a reduction of erythroid cell proliferation, as shown by decreased proportions of circulating reticulocytes and by reduced iron 59 ((59)Fe) incorporation into erythroid tissues. This study indicates that the continuous delivery of high amounts of autologous erythropoietin induced a sustained stimulation of beta-minor globin synthesis and a stable improvement of erythropoiesis in the beta-thalassemic mouse model. (Blood. 2000;95:2793-2798)

Animals↗
PubMed2000

Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.

Hereditary paraganglioma (PGL) is characterized by the development of benign, vascularized tumors in the head and neck. The most common tumor site is the carotid body (CB), a chemoreceptive organ that senses oxygen levels in the blood. Analysis of families carrying the PGL1 gene, described here, revealed germ line mutations in the SDHD gene on chromosome 11q23. SDHD encodes a mitochondrial respiratory chain protein-the small subunit of cytochrome b in succinate-ubiquinone oxidoreductase (cybS). In contrast to expectations based on the inheritance pattern of PGL, the SDHD gene showed no evidence of imprinting. These findings indicate that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.

Alleles↗
PubMed2000

Long-term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors.

Most lysosomal storage diseases, including mucopolysaccharidosis, affect the central nervous system (CNS). They often induce severe and progressive mental retardation. Replacement therapy by purified enzyme infusions is a promising approach for the treatment of peripheral organs but without effect on CNS pathology because the enzyme cannot cross the blood-brain barrier. Intracranial injection of recombinant adeno-associated virus (AAV) vectors offers an alternative for sustained local enzyme delivery from genetically engineered cells. We stereotactically injected an AAV vector containing the human beta-glucuronidase cDNA into the striatum of adult mice severely affected by mucopolysaccharidosis type VII at the time of treatment. Six weeks later, beta-glucuronidase activity in the injected hemisphere was comparable to that of heterozygous mice, which have a normal phenotype. Areas staining positive for enzyme activity enlarged with time, representing more than 10% of the hemisphere volume by 16 weeks. A complete reversion of lysosomal storage lesions was evident in these areas, as well as in most neurons located in surrounding negative areas and in the noninjected hemisphere. Thus, a single intracerebral injection of AAV vectors could achieve a broad and sustained lysosomal enzyme delivery, allowing for stable reversion of storage lesions in a significant fraction of the adult brain.

Animals↗
PubMed2000

Screening for BRCA2 mutations in 81 Dutch breast-ovarian cancer families.

We have analysed 81 families with a history of breast and/or ovarian cancer for the presence of germline mutations in BRCA2 with a number of different mutation screening techniques. The protein truncation test (PTT) for exons 10 and 11 detected four different frame-shifting mutations in six of these families. Four of the remaining 75 families had given positive linkage evidence for being due to BRCA2. In these families the entire coding region was analysed by single-strand conformational polymorphism, leading to the detection of a non-sense and a splice-site mutation in two of them. While these studies were in progress, Southern analysis of BRCA1 revealed that in our study-population of 81 families, 15 families were segregating either the exon 13 or exon 22 deletion in BRCA1 (Petrij-Bosch et al (1997) Nat Genet 17: 341-345). This prompted us to examine BRCA2 in the remaining 58 families by Southern analysis, using two different restriction enzymes. No aberrations were found in the restriction patterns. Thus, contrary to BRCA1, large genomic rearrangements within the BRCA2 gene do not represent a major mutation mechanism among Dutch breast cancer families.

BRCA2 Protein↗
PubMed2000

Cerebral autoregulation in subjects adapted and not adapted to high altitude.

BACKGROUND AND PURPOSE: Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude. METHODS: We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP. RESULTS: In the sea-level group, at a relative MABP increase of 23+/-4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2+/-7%, P=0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29+/-7%, there was a uniform and significant increase of Vmca of 24+/-9% (P<0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21+/-6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%. CONCLUSIONS: All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.

Adaptation, Physiological↗
PubMed1999

A high-resolution physical map of human chromosome 21p using yeast artificial chromosomes.

The short arm of human chromosome 21 (21p) contains many different types of repetitive sequences and is highly homologous to the short arms of other acrocentric chromosomes. Owing to its repetitive nature and the lack of chromosome 21p-specific molecular markers, most physical maps of chromosome 21 exclude this region. We constructed a physical map of chromosome 21p using sequence tagged site (STS) content mapping of yeast artificial chromosomes (YACs). To this end, 39 STSs located on the short arm or near the centromere of chromosome 21 were constructed, including four polymorphic simple tandem repeats (STRs) and two expressed sequence tags (ESTs). Thirty YACs were selected from the St. Louis YAC library, the chromosome 21-enriched ICRF YAC library, and the CEPH YAC and megaYAC libraries. These were assembled in a YAC contig map ranging from the centromere to the rDNA gene cluster at 21p12. The total size of the region covered by YACs is estimated between 2.9 and 5 Mb. The integrity of the YAC contig was confirmed by restriction enzyme fingerprinting and fluorescence in situ hybridization (FISH). One gap with an estimated size of 400 kb remained near the telomeric end of the contig. This YAC contig map of the short arm of human chromosome 21 constitutes a basic framework for further structural and functional studies of chromosome 21p.

Chromosomes, Artificial, Yeast↗
PubMed1999

Group D adenoviruses infect primary central nervous system cells more efficiently than those from group C.

Group C adenovirus-mediated gene transfer to central nervous system cells is inefficient. We found that wild-type group D viruses, or recombinant adenovirus type 2 (Ad2) (group C) modified to contain Ad17 (group D) fiber, were more efficient in infecting primary cultures of neurons. Together with studies on primary vascular endothelial cells and tissue culture cell lines, our results indicate that there is not a universally applicable adenovirus serotype for use as a gene transfer vector.

Adenoviruses, Human↗
PubMed1998

Enhancement of the immunogenicity of a synthetic peptide bearing a VP3 epitope of hepatitis A virus.

The immune responses elicited in mice by different forms of the VP3(110-121) B-epitope of the hepatitis A virus (HAV) were studied. Different forms of incorporation in liposomes were tested, encapsulation, rather than surface exposure, being the best antigenic preparation. Three larger peptides of the VP3 epitope, two of them containing a hepatitis B virus T-epitope, and a third containing a putative T-epitope of HAV (VP3(102-121)) were assayed. While this latter T-epitope induced an enhancement of the response against the VP3 B-epitope, the artificially coupled T-epitopes failed to induce a significant increase. The administration of two multiple antigenic peptide (MAP) constructs, the first containing the VP3(110-121) and VP1(11-25) HAV sequences and the second only the VP1(11-25) sequence, also suggested the presence of a T-epitope, since the response against the VP1 peptide was increased in the first construct.

Animals↗
PubMed1998

Effects of keratinocyte and hepatocyte growth factor in vivo: implications for retrovirus-mediated gene transfer to liver.

We have previously shown that intravenous administration of keratinocyte growth factor (KGF) induces hepatocyte proliferation, allowing for efficient and noninvasive in vivo gene transfer with high-titer retroviral vectors in mice. The distinctive periportal distribution of transduced cells led us to investigate the ability of virus-sized particles to perfuse the liver adequately after growth factor treatment. We found that perfusion was adequate, and that transduction was limited to the periportal region because only those cells were stimulated to divide. Cells in this region also showed increased expression of Ram-1, the receptor for the murine Moloney leukemia virus (MoMLV) amphotropic envelope, after KGF treatment. In further studies we found that recombinant hepatocyte growth factor (HGF) induces a different population of hepatocytes to divide and upregulate Ram-1. The differential pattern of induction suggested that combining KGF and HGF would improve gene transfer efficiency further. Indeed, simultaneous delivery of both growth factors leads to an overall increase in the number of proliferating cells. Importantly, when coupled with MoMLV delivery, efficiency of gene transfer increased. These results confirm the utility of growth factors for noninvasive hepatic gene transfer in mice, and demonstrate how experiments to define the mechanism of transduction can be taken advantage of to develop improved gene transfer protocols.

Animals↗
PubMed1998

A new continuous epitope of hepatitis A virus.

A new continuous epitope of hepatitis A virus (HAV) was defined in the VP3 protein. Convalescent sera recognised the synthetic peptide 3110-3121 (FWRGDLVFDFQV). The replacement of the arginine, glycine, or aspartic acid at positions 112, 113, or 114, respectively by other amino acids induced the loss of synthetic peptide recognition by human convalescent sera, thereby confirming the presence of an epitope in the original VP3(110-121) sequence. Shorter VP3 peptides such as VP3(110-119). VP3(110-117), and VP3(110-116) and a tandem repeat of VP3(111-116) failed to react with convalescent sera, indicating the importance of the entire peptide in the epitope structure. The maximum inhibition of human convalescent binding to HAV by the VP3(110-121) peptide was around 60%, and 50% inhibition was achieved at a peptide concentration of 2.3-2.4 micrograms/ml. Antibodies generated by this peptide bound to intact HAV and neutralised its infectivity. Antipeptide antibodies inhibited convalescent serum binding to HAV. Monoclonal antibodies H7C27 and MAK-4E7 inhibited completely binding of the antipeptide antibodies to HAV.

Antibodies, Monoclonal↗