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Biomedical subjects

A Gabriel

Publications and source records attributed to A Gabriel.

At least 19 recordsLinked to original sources
PubMed2007

A mouse model of basal-like breast carcinoma with metaplastic elements.

Breast cancers arising in carriers of germline BRCA1 mutations frequently have a basal-like phenotype. Basal-like cancers are characterized by high histological grade, central necrotic areas, foci with metaplastic differentiation, lack of hormone receptor and HER2 (ErbB2) expression, and consistent positivity for basal markers, including CK5/6, CK14, and EGFR. We have used germline manipulation to generate a conditional mouse model of Brca1 deficiency. Transgenic expression of Cre recombinase in the mammary gland of these mice results in deletion of exons encoding the C-terminus of Brca1 and leads to tumour formation when combined with heterozygosity for a p53 mutation. Histologically, these mammary gland tumours were characterized by high histological grade, central necrotic areas, and presence of homologous metaplastic elements. These metaplastic elements consisted of neoplastic spindle cells or squamous cell differentiation in the form of keratin pearls or individual cell keratinization. Immunohistochemical analysis revealed expression of basal-like markers in all cases. The tumour phenotype generated in our mouse model was compared with published data on human basal-like breast carcinomas and also with metaplastic breast cancers with a basal-like phenotype; the comparison showed that we have generated a mouse model of basal-like breast cancer, which should prove useful in testing new and targeted treatments for this type of breast cancer.

Animals↗
PubMed2006

Prevalence of elevated blood pressure and association with overweight in children of a rapidly developing country.

We assessed the prevalence of elevated blood pressure (BP) and the association with excess body weight among a large sample of children in the Seychelles, a middle-income rapidly developing country in the African region. Weight, height and BP were measured in all children of four school grades in the Seychelles (Indian Ocean). Excess weight categories ('overweight' and 'obesity') were defined according to the criteria of the International Obesity Task Force. Two BP readings were obtained on one occasion. 'Elevated BP' was defined based on US reference tables. Data were available in 15,612 (86%) of 18,119 eligible children aged 5-16 years in 2002-2004. In all, 13.0% of Boys and 18.8% of girls were overweight or obese. The prevalence of elevated BP was 9.1% in boys and 10.1% in girls. Both systolic and diastolic BP were strongly associated with body mass index (BMI) in boys and in girls. In children with 'normal weight', 'overweight (and not obesity)' and 'obesity', respectively, proportions with elevated BP were 7.5, 16.9 and 25.2% in boys, and 7.5, 16.1 and 33.2% in girls. Overweight (including obesity) could account for 18% of cases of elevated BP in boys and 26% in girls. Further studies should examine the impact of the relationship between BMI and elevated BP on the burden of hypertension in the context of the epidemic of paediatric obesity.

Adolescent↗
PubMed2006

Changes in plasma cholesterol in mood disorder patients: does treatment make a difference?

OBJECTIVES: To examine the impact of treatment in patients with acute episodes of major depressive (MD) and manic or hypomanic (M/HM) episodes and co-morbid generalized anxiety symptoms, on the total cholesterol blood levels (TC). METHOD: A consenting series of patients with acute episodes of DSM IV-R confirmed diagnosis of MD or M/H were included. Subjects were treated with antidepressants, mood stabilizers, or both. The Hamilton depression scale (HAM-D21), the modified mania rating scale (MMRS), and the Hamilton anxiety scale (HAM-A) were utilized to evaluate clinical symptoms. Blood samples were drawn for TC estimations after 10 h of fasting on two occasions over time. The first sample was taken before treatment was started, and the second 4 weeks after treatment. The relationship between changes in TC and the severity of psychiatric symptoms, as measured on HAM-D, MMRS, and the HAM-A, were analysed. RESULTS: 56 subjects (34 with MD and 22 with M/HM episodes) completed the study. About 4 weeks after treatment there was a statistically significant increase in the TC in patients with MD versus a significant decrease in patients with M/HM episodes. CONCLUSION: Our results replicate earlier reports of significant increase in the cholesterol levels in depressed patients after treatment. We report a significant decrease of TC levels in M/HM episodes with treatment. Although the results in previous reports and in our study are statistically significant, their clinical significance requires further examination in longer-term studies.

Acute Disease↗
PubMed2006

Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs.

OBJECTIVES: To characterise clinical, electrophysiological and histopathological findings. To analyse pedigree information in six young related Pyrenean mountain dogs with laryngeal paralysis-polyneuropathy complex (LP-PNC). METHODS: A retrospective study of clinical records and pedigrees of six young related Pyrenean mountain dogs with LP-PNC was carried out. RESULTS: All dogs were presented with laryngeal paralysis and concurrent megaoesophagus. Electrodiagnostic testing was performed in three dogs and showed electrophysiological abnormalities in the distal appendicular muscles. Histopathological findings of peripheral nerve samples were dominated by distal axonal degeneration. Clinical, electrophysiological and histopathological findings were supportive of a diagnosis of degenerative, sensorimotor LP-PNC, similar to that reported in young dalmatians and rottweilers. All dogs died or were euthanased by two years of age. An autosomal recessive mode of inheritance was suspected based on pedigree analysis. CLINICAL SIGNIFICANCE: Congenital LP-PNC should be suspected in any young dog presenting with laryngeal dysfunction and other concurrent neurological abnormalities. The prognosis is usually poor.

Animals↗
PubMed2006

Suspected drug-induced destructive cholangitis in a young dog.

A nine-month-old miniature doberman was referred for the evaluation of chronic icterus. History and clinical and histopathological findings were supportive of a diagnosis of drug-induced destructive cholangitis. The main histopathological findings were canalicular, centrilobular cholestasis and ductopenia with moderate inflammatory infiltrate. The dog had received three types of treatment for demodicosis before the onset of jaundice. Amoxicillin-clavulanate, amitraz, milbemycin oxime or an interaction between two of the three drugs may have been responsible for the destructive cholangitis.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2005

Reverse transcriptase and integrase of the Saccharomyces cerevisiae Ty1 element.

Integrase (IN) and reverse transcriptase (RT) play a central role in transposition of retroelements. The mechanism of integration by IN and the steps of the replication process mediated by RT are briefly described here. Recently, active recombinant forms of Ty1 IN and RT have been obtained. This has allowed a more detailed understanding of their biochemical and structural properties and has made possible combined in vitro and in vivo analyses of their functions. A focus of this review is to discuss some of the results obtained thus far with these two recombinant proteins and to propose future directions.

Amino Acid Sequence↗
PubMed2004

Leukotrienes mediate 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint via CysLT-type receptors.

OBJECTIVE AND DESIGN: The aim of this study was to investigate whether leukotrienes synthesized by 5-lipoxygenase (5-LO) and acting via leukotriene (LT) receptors contribute to 5-hydroxytryptamine (5-HT)-induced knee joint plasma extravasation (PE). MATERIALS AND METHODS: Knee joints of rats under anesthesia were perfused with 5-HT and synovial vascular Evans Blue dye leakage was measured spectrophotometrically. A series of 5-LO inhibitors and LT receptor antagonists were investigated for their ability to inhibit 5-HT-induced synovial PE. RESULTS: Inhibitors of 5-LO (NDGA and REV 5901) significantly attenuated 5-HT-induced plasma extravasation. MK 571, LY 171883, BAY u9773 (CysLT receptor antagonists) and REV 5901 (a CysLT receptor antagonist and a 5-LO inhibitor) were equally effective in inhibiting 5-HT-induced PE, indicating that leukotrienes mediate 5-HT-induced PE via CysLT receptors. In contrast, antagonists selective for LTB(4) receptors (BLT(1) and BLT(2) receptors) failed to reduce 5-HT-induced PE. CONCLUSIONS: These results demonstrate that leukotrienes, specifically cysteinyl-leukotrienes contribute to synovial plasma extravasation and suggest that leukotrienes act downstream of 5-HT in the inflammatory cascade.

Animals↗
PubMed2004

[Regulation of spinal nociceptin expression by neuropathic pain].

Nociceptin is the endogenous ligand of a new opioid receptor, the opioid receptor-like-1 (ORL1) receptor. Chronic inflammatory pain causes an increase in the expression of nociceptin and the ORL1 receptor in the dorsal horn of rat spinal cord, thus indicating an involvement of the endogenous nociceptin/ORL1 system in mechanisms of pathological pain. This study investigates the influence of neuropathic pain on the expression of nociceptin using immunohistochemistry. To induce neuropathic pain, a ligation of the sciatic nerve was performed in 12 rats under general anesthesia. A sham operation was performed in 12 rats of the control group. Nerve ligation caused a significant ipsilateral thermal hyperalgesia, a typical sign of neuropathic pain. The paw withdrawal latency was decreased by 45.7+/-4.9% ( p<0.05) at day 5 and by 37.3+/-1.8% ( p<0.05) at day 10. Although hyperalgesia was fully present after 5 days, no changes in nociceptin immunoreactivity in the lumbar spinal cord were detected at this time point. Ten days after nerve ligation, there was a 2.46+/-0.38 fold ( p<0.05) bilateral increase in nociceptin immunoreactivity in the lamina superficiales (I and II), with a notable increase in the inner lamina II at the level of L4. Further investigations are necessary to elucidate the relationship between neuropathic pain, the nociceptin-ORL1 receptor system and potential therapeutic options.

Animals↗
PubMed2003

Effect of antibodies to intercellular adhesion molecule type 1 on the protection of distant organs during reperfusion syndrome in rats.

We investigated kidney and lung alterations caused by intercellular adhesion molecule type 1 (ICAM-1) blockade after ischemia and reperfusion of hind limb skeletal muscles. Rats were submitted to ligature of the infrarenal aorta for 6 h. The animals were randomized into three groups of 6 rats each: group I, sacrificed after ischemia; group II, reperfusion for 24 h, and group III, reperfusion for 24 h after receiving monoclonal anti-ICAM-1 antibodies. At the end of the experiment, blood samples were collected for creatinine, lactate dehydrogenase, creatine phosphokinase, potassium, pH and leukocyte counts. Samples were taken from the muscles of the hind limbs and from the kidneys and lungs for histological analysis and measurement of the neutrophil infiltrate by myeloperoxidase staining. The groups did not differ significantly with regard to the laboratory tests. There were no major histological alterations in the kidneys. An intense neutrophil infiltrate in the lungs, similar in all groups, was detected. Myeloperoxidase determination showed that after reperfusion there was significantly less retention of polymorphonuclear neutrophils in the muscles (352 +/- 70 vs 1451 +/- 235 x 10(2) neutrophils/mg; P<0.01) and in the kidneys (526 +/- 89 vs 852 +/- 73 10(2) neutrophils/mg; P<0.01) of the animals that received anti-ICAM-1 before perfusion compared to the group that did not. The use of anti-ICAM-1 antibodies in this experimental model minimized neutrophil influx, thus reducing the inflammatory process, in the muscles and kidneys after ischemia and reperfusion of the hind limbs.

Animals↗
PubMed2003

5-Hydroxytryptamine-induced plasma extravasation in the rat knee joint is mediated by multiple prostaglandins.

OBJECTIVE AND DESIGN: This study investigated whether prostaglandins (PGs) are involved in 5-hydroxytryptamine (5-HT)-induced synovial plasma extravasation. MATERIALS AND METHODS: Male Sprague-Dawley rat knee joints were perfused with 5-HT and synovial capillary Evans Blue dye leakage was measured using spectrophotometry. Cyclooxygenase (COX) inhibitors and PG receptor subtype-selective antagonists were tested for the ability to reduce 5-HT-induced synovial plasma extravasation. RESULTS: 5-HT-induced plasma extravasation was inhibited by indomethacin. The COX-1 selective inhibitor SC-560 and the COX-2 selective inhibitor NS-398 were equally effective, indicating that both isoforms are involved. Antagonists selective for EP1, EP2 and DP receptor subtypes significantly attenuated the 5-HT-induced plasma extravasation. However, antagonists selective for FP, IP and TP subtypes failed to reduce 5-HT-induced plasma extravasation. CONCLUSIONS: These results demonstrate that multiple, but selective, subtypes of PGs mediate synovial plasma extravasation produced by 5-HT, and suggest that PGs act downstream of 5-HT in the inflammatory cascade.

Animals↗
PubMed2003

The course of some bone remodelling plasma metabolites in healthy horses and in horses offered a calcium-deficient diet.

An inquiry was carried out to assess the concentrations of plasma metabolites related to bone remodelling in 21 saddle horses of Warmblood breed aged 4-26 years, five draught horses of Ardennes breed aged 4-10 years, and 10 Ardennes foals aged 9-11 months. They were fed according to normal feeding practice in Belgium. The changes in some bone remodelling plasma metabolite concentrations were studied when an unbalanced diet was offered and later corrected for four Warmblood horses. Bone formation was evaluated by bone alkaline phosphatase (BALP), total alkaline phosphatase (TALP) and osteocalcin (bone gla-protein, OC). Bone resorption was assessed by hydroxyproline (HYP). Total calcium, ionized calcium, phosphorus (P) and 25-hydroxyvitamin D3 [25-(OH)D] concentrations were more or less constant. The comparison of four bone remodelling factors between the Ardennes and Warmblood horses showed higher concentrations in the Ardennes breed. Bone marker concentrations decreased according to age. The correction of the unbalanced Ca : P diet induced inconsistent effects at plasma level. The interpretation of the different bone parameters appeared to be difficult if not associated with other parameters such as a complete anamnesis and clinical examination of the animal in addition to dietary evaluation.

Age Factors↗
PubMed2003

Heterogeneity of stage IIIA non-small cell lung cancers (NSCLC) and evaluation of late results of surgical treatment.

AIMS: The aim of the study was assessment of the heterogeneity of stage IIIA non-small cell lung cancers (NSCLC) and the late results of surgical treatment. METHODS: The study group consisted of 83 consecutive patients discharged between 1988 and 1992 undergoing radical operative treatment for stage IIIA NSCLC. Squamous cell carcinoma was diagnosed in 54 (65.1%) patients, adenocarcinoma in 23 (27.7%), large cell carcinoma in 2 (2.4%) and mixed (i.e. adenoid-squamous type) in 4 (4.8%). In respect of pTNM staging, 19 (22.9%) patients had T3N1M0, 35 (42.2%) had T2N2M0 and 29 (34.9%) had T3N2M0. RESULTS: Overall, 13.3% of patients with stage IIIA NSCLC survived 5 years following the operation and 8.7% survived 10 years. Analysis of follow-up study indicated that this group was heterogenic. In T3N1M0 group 26.3% survived 5 years following the operation, in T2N2M0 group 14.3%, in T3N2M0 group 3.5% (P = 0.015). Of 23 patients with N2 disease and no metastases in hilar lymph nodes ('skip' metastases), 26.1% survived 5 years, whereas none of 41 patients with metastases spreading by continuity survived (P = 0.0015). If mediastinal lymph node metastases were diagnosed in one level, 25% patients survived 5 years, but if two or more levels were affected, 2.3% only (P = 0.0214): 85.7% of patients with well-differentiated (G1) cancer survived 5 years and 62.0% 10 years, whereas among those with moderately differentiated (G2) tumours, 11.8% and 8.8%, respectively. No patient survived 5 years after resection of poorly differentiated (G3) cancer (P < 0.001). CONCLUSIONS: (1) Patients operated for stage IIIA NSCLC are a heterogeneous group, which makes it difficult to predict late results. (2) Patients operated for stage IIIA NSCLC have a better prognosis if metastases are discovered in level one mediastinal lymph nodes, particularly in the superior part of mediastinum, or if 'skip' metastases (pulmonary hilus unaffected) are discovered, as compared to those with N2 disease. (3) Poor histologic differentiation of the tumour is a bad prognostic factor.

Adenocarcinoma↗
PubMed2002

Paradoxical sleep deprivation increases plasma endothelin levels.

The endothelins (ET-1, 2 and 3) constitute a family of 21 amino acid peptides with potent biological activities. ET-1 is one of the most potent endogenous vasoconstrictors so far identified and its increased concentration in plasma appears to be closely related to the pathogenesis of arterial hypertension as well as to obstructive sleep apnea (OSA). OSA patients exhibit repetitive episodes of apnea and hypopnea that result in hypoxia and consecutive arousals. These patients are chronically sleep deprived, which may aggravate the hypertensive features, since literature data show that sleep deprivation results in hypertension both in humans and in animals. Based on the reported relationship between ET-1, hypertension and sleep deprivation consequences, the purpose of the present study was to determine plasma ET concentrations in paradoxical sleep-deprived animals. Male Wistar rats, 3 to 4 months old (N = 10 per group), were deprived of sleep for 24 and 96 h by the platform technique and plasma ET-(1/2) was measured by radioimmunoassay. Analysis of plasma revealed that 96 h of sleep deprivation induced a significant increase in ET-(1/2) release (6.58 fmol/ml) compared to control (5.07 fmol/ml). These data show that sleep deprivation altered plasma ET-(1/2) concentrations, suggesting that such an increase may participate in the genesis of arterial hypertension and cardiorespiratory changes observed after sleep deprivation.

Analysis of Variance↗
PubMed2001

Polypurine tract formation by Ty1 RNase H.

To better understand the mechanism by which Ty1 RNase H creates the polypurine tract (PPT) primer, we have demonstrated the polymerase-dependent hydrolytic activity of Ty1 reverse transcriptase (RT) during minus-strand synthesis. Using RNase H and polymerase mutants of the recombinant Ty1 RT protein, we show that the two domains of Ty1 RT can act independently of one another. Our results indicate that RNA/DNA substrates containing a short RNA PPT, which serve as primers for plus-strand DNA synthesis, are relatively resistant to RNase H cleavage. RNA substrates with a correct 5' end but with 3' end extending beyond the plus-strand initiation site were cleaved specifically to generate the correct 3' end of the PPT. Using long RNA/DNA duplexes containing the PPT, we show that Ty1 RT is able to make specific internal cleavages that could generate the plus-strand primer with correct 5' and 3' ends. Long RNA/DNA duplexes with mutations in the PPT or in a U-rich region upstream of the PPT, which abolish plus-strand initiation in vivo, were not cleaved specifically at the 5' end of the PPT. Our work demonstrates that the in vitro enzyme can recapitulate key processes that control proper replication in vivo.

Base Sequence↗
PubMed2001

Blockade effects of (Nphe1)Nociceptin(1-13)-NH(2) on anti-nociception induced by intrathecal administration of nociceptin in rats.

The present study investigated the roles of the opioid-receptor-like (ORL1) receptor and its endogenous ligand nociceptin on nociception in the spinal cord of rats. Intrathecal administration of 10 nmol of nociceptin produced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation. There were no significant changes of average maximum angles in inclined plane tests after intrathecal injection of 10 nmol of nociceptin in rats. The intrathecal nociceptin-induced increases in HWL were antagonized by intrathecal administration of (Nphe1)Nociceptin(1-13)-NH(2), a selective antagonist of ORL1 receptor, in a dose-dependent manner. The results demonstrated that ORL1 receptor is involved in the nociceptin-induced anti-nociceptive effect in the spinal cord of rats.

Animals↗
PubMed2001

Latency and reactivation of a glycoprotein E negative bovine herpesvirus type 1 vaccine: influence of virus load and effect of specific maternal antibodies.

The effects of the vaccination of neonatal calves with a glycoprotein E (gE)-negative bovine herpesvirus type 1 (BHV-1) were investigated in naïve and passively immunised calves either with the recommended dose or a 5-fold concentrated one. After inoculation (PI), all calves excreted the virus vaccine except three passively immunised calves inoculated with the lower titre. No antibody response could be detected in passively immunised calves, whatever the dose used, and they all became BHV-1 seronegative and remained so after dexamethasone treatment (PDT). Nevertheless, as shown by a gamma-interferon assay, all calves that excreted the vaccine PI developed a cell-mediated immune response and a booster response was observed PDT, suggesting viral reactivation. The vaccine virus was recovered PDT from nasal secretions in two calves and BHV-1 DNA were detected in trigeminal ganglia from five calves belonging to all inoculated groups. The results show that the BHV-1 gE-negative vaccine can establish latency not only in naïve but also in passively immunised neonatal calves after a single intranasal inoculation. Moreover, this study shows for the first time that the gE-negative vaccine, when used in passively immunised calves, can lead to seronegative vaccine virus carriers.

Animals↗
PubMed2001

Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences.

Mutation of BRCA2 causes familial early onset breast and ovarian cancer. BRCA2 has been suggested to be important for the maintenance of genome integrity and to have a role in DNA repair by homology- directed double-strand break (DSB) repair. By studying the repair of a specific induced chromosomal DSB we show that loss of Brca2 leads to a substantial increase in error-prone repair by homology-directed single-strand annealing and a reduction in DSB repair by conservative gene conversion. These data demonstrate that loss of Brca2 causes misrepair of chromosomal DSBs occurring between repeated sequences by stimulating use of an error-prone homologous recombination pathway. Furthermore, loss of Brca2 causes a large increase in genome-wide error-prone repair of both spontaneous DNA damage and mitomycin C-induced DNA cross-links at the expense of error-free repair by sister chromatid recombination. This provides insight into the mechanisms that induce genome instability in tumour cells lacking BRCA2.

Alleles↗