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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 253 records · Page 14Linked to original sources
PubMed1998

Apnoea-associated heart rate changes among preterm and full-term infants exposed to hyperthermia.

Heart rate (HR) changes associated with apnoea (> 3 s) were analysed in 10 preterm infants (30.6 +/- 1.5 weeks) at post-conceptional age of 40 +/- 1.5 weeks and 10 full-term (FT) infants (39 +/- 1 weeks) before, during and after exposure to increased environmental temperature (5 degrees C above normothermia). A significantly increased HR was found in the study group during the baseline (normothermia), heating, cooling and final normothermic phase compared with the control infants. No significant difference was found between the groups during the hyperthermic stage. A significant relative increase in HR was found among the preterm infants but not among FT infants during central apnoea at the hyperthermia phase. Our results indicate that HR control during apnoea in preterm infants is more labile then among FT infants while being exposed to increased environmental temperature.

Apnea↗
PubMed1998

Chi-dependent intramolecular recombination in Escherichia coli.

Homologous recombination in Escherichia coli is enhanced by a cis-acting octamer sequence named Chi (5'-GCTGGTGG-3') that interacts with RecBCD. To gain insight into the mechanism of Chi-enhanced recombination, we recruited an experimental system that permits physical monitoring of intramolecular recombination by linear substrates released by in vivo restriction from infecting chimera phage. Recombination of the released substrates depended on recA, recBCD and cis-acting Chi octamers. Recombination proficiency was lowered by a xonA mutation and by mutations that inactivated the RuvABC and RecG resolution enzymes. Activity of Chi sites was influenced by their locations and by the number of Chi octamers at each site. A single Chi site stimulated recombination, but a combination of Chi sites on the two homologs was synergistic. These data suggest a role for Chi at both ends of the linear substrate. Chi was lost in all recombinational exchanges stimulated by a single Chi site. Exchanges in substrates with Chi sites on both homologs occurred in the interval between the sites as well as in the flanking interval. These observations suggest that the generation of circular products by intramolecular recombination involves Chi-dependent processing of one end by RecBCD and pairing of the processed end with its duplex homolog.

Bacteriophages↗
PubMed1998

Behavioural problems among visually impaired between 6 months and 5 years.

The prevalence and types of behavioural problems among legally blind children were assessed by employing a cohort study design in a well defined geographic area. One hundred and eighty two children between the ages of 6 months and 5 years were consecutively assessed over a period of 13 years. A standardized ophthalmological, neurodevelopmental and physical examination, a parental interview and video recording were employed. Diagnostic classification was based on the DSM-III-R criteria (American Psychiatric Association, 1987). Behavioural problems were documented in 49%. In 61% of these, three disorders were identified: (1) overanxious (n = 14), (2) oppositional with or without attention deficit hyperactivity (n = 15), and avoidant with or without stereotypy (n = 26). The first category is associated with partial sightedness and the third with neurodevelopmental deficits. The prevalence of behavioural problems among blind children is high and therefore a careful psychological monitoring and assistance should be offered to them and their parents.

Blindness↗
PubMed1998

Three cdg operons control cellular turnover of cyclic di-GMP in Acetobacter xylinum: genetic organization and occurrence of conserved domains in isoenzymes.

Cyclic di-GMP (c-di-GMP) is the specific nucleotide regulator of beta-1,4-glucan (cellulose) synthase in Acetobacter xylinum. The enzymes controlling turnover of c-di-GMP are diguanylate cyclase (DGC), which catalyzes its formation, and phosphodiesterase A (PDEA), which catalyzes its degradation. Following biochemical purification of DGC and PDEA, genes encoding isoforms of these enzymes have been isolated and found to be located on three distinct yet highly homologous operons for cyclic diguanylate, cdg1, cdg2, and cdg3. Within each cdg operon, a pdeA gene lies upstream of a dgc gene. cdg1 contains two additional flanking genes, cdg1a and cdg1d. cdg1a encodes a putative transcriptional activator, similar to AadR of Rhodopseudomonas palustris and FixK proteins of rhizobia. The deduced DGC and PDEA proteins have an identical motif structure of two lengthy domains in their C-terminal regions. These domains are also present in numerous bacterial proteins of undefined function. The N termini of the DGC and PDEA deduced proteins contain putative oxygen-sensing domains, based on similarity to domains on bacterial NifL and FixL proteins, respectively. Genetic disruption analyses demonstrated a physiological hierarchy among the cdg operons, such that cdg1 contributes 80% of cellular DGC and PDEA activities and cdg2 and cdg3 contribute 15 and 5%, respectively. Disruption of dgc genes markedly reduced in vivo cellulose production, demonstrating that c-di-GMP controls this process.

Amino Acid Sequence↗
PubMed1998

Virion-targeted viral inactivation of human immunodeficiency virus type 1 by using Vpr fusion proteins.

Inactivation of progeny virions with chimeric virion-associated proteins represents a novel therapeutic approach against human immunodeficiency virus (HIV) replication. The HIV type 1 (HIV-1) Vpr gene product, which is packaged into virions, is an attractive candidate for such a strategy. In this study, we developed Vpr-based fusion proteins that could be specifically targeted into mature HIV-1 virions to affect their structural organization and/or functional integrity. Two Vpr fusion proteins were constructed by fusing to the first 88 amino acids of HIV-1 Vpr the chloramphenicol acetyltransferase enzyme (VprCAT) or the last 18 C-terminal amino acids of the HIV-1 Vpu protein (VprIE). These Vpr fusion proteins were initially designed to quantify their efficiency of incorporation into HIV-1 virions when produced in cis from the provirus. Subsequently, CD4+ Jurkat T-cell lines constitutively expressing the VprCAT or the VprIE fusion protein were generated with retroviral vectors. Expression of the VprCAT or the VprIE fusion protein in CD4+ Jurkat T cells did not interfere with cellular viability or growth but conferred substantial resistance to HIV replication. The resistance to HIV replication was more pronounced in Jurkat-VprIE cells than in Jurkat-VprCAT cells. Moreover, the antiviral effect mediated by VprIE was dependent on an intact p6(gag) domain, indicating that the impairment of HIV-1 replication required the specific incorporation of Vpr fusion protein into virions. Gene expression, assembly, or release was not affected upon expression of these Vpr fusion proteins. Indeed, the VprIE and VprCAT fusion proteins were shown to affect the infectivity of progeny virus, since HIV virions containing the VprCAT or the VprIE fusion proteins were, respectively, 2 to 3 times and 10 to 30 times less infectious than the wild-type virus. Overall, this study demonstrated the successful transfer of resistance to HIV replication in tissue cultures by use of Vpr-based antiviral genes.

Gene Products, vpr↗
PubMed1998

Protein kinase G is not essential to NO-cGMP modulation of basal tone in rat pulmonary circulation.

Nitric oxide (NO) is important in modulating increased pulmonary vascular tone. Whereas in other systems it is believed that the action of NO is mediated through guanosine 3',5'-cyclic monophosphate (cGMP) and protein kinase G (PKG), the validity of this pathway in the pulmonary circulation has not been established. Using isolated salt-perfused normotensive and hypertensive rat lungs, we studied the effects of the soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and the PKG inhibitors, KT5823, Rp-8-pCPT-cGMPS, and (N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide) (H-8), on pulmonary vascular resistance. In isolated normotensive lungs, ODQ-mediated inhibition of soluble guanylyl cyclase augmented hypoxic pulmonary vasoconstriction, whereas the PKG inhibitors had no effect. Despite the marked differences in the physiological effect, ODQ and Rp-8-pCPT-cGMPS inhibited PKG activity to a similar degree as determined by a back-phosphorylation assay showing decreased PKG-mediated phosphorylation of serine 1755 on the D-myo-inositol 1,4,5-trisphosphate receptor. In hypertensive lungs, inhibition of soluble guanylyl cyclase by ODQ increased perfusion pressure by 101 +/- 20% (P < 0.05), an increase similar to that seen with inhibition of NO synthase (NOS), confirming an essential role for cGMP. In contrast, KT5823, Rp-8-pCPT-cGMPS, and H-8 (used in doses 5- to 100-fold in excess of their reported inhibitory concentrations for PKG) caused only a small increase in baseline perfusion pressure (14 +/- 2%, P = not significant from vehicle control). Effectiveness of PKG inhibition in the hypertensive lungs was also confirmed with the back-phosphorylation assay. These studies suggest that whereas NO-mediated modulation of vascular tone in the normotensive and hypertensive pulmonary circulation is dependent on cGMP formation, activation of PKG may not be essential.

Alkaloids↗
PubMed1998

Plasma antioxidants: evidence for a protective role against reactive oxygen species following cardiac surgery.

Total plasma antioxidant status (TPAS), lipid peroxide concentration (LPX) and cardiac troponin T (cTnT) were measured in 24 patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Samples were obtained preoperatively and at 1.5 h, 6 h, 24 h and 72 h after CPB. The absolute TPAS values were significantly lower at 1.5 h, 6 h, 24 h and 72 h after CPB than were preoperative values (P < 0.05). The LPX concentration was significantly elevated at 1.5 h after CPB (P < 0.05). Cardiac troponin T concentrations were significantly elevated at all time points postoperatively (P < 0.05). Preoperative TPAS values were significantly correlated with the magnitude of fall in TPAS at 1.5 h (P < 0.05). The greater the fall in TPAS between 0 and 1.5 h, the less LPX was formed between 0 and 1.5 h. The LPX at 1.5 h displayed a significant correlation with cTnT release from myocardial myocytes (P < 0.05). These data provide evidence for the first time that the consumption of antioxidants during CABG surgery with CPB protects against the production of reactive oxygen species and subsequent myocyte necrosis. Furthermore, the availability of protective antioxidants is dependent upon preoperative TPAS.

Adult↗
PubMed1998

Learning disabilities with and without attention-deficit hyperactivity disorder: parents' and teachers' perspectives.

Our objective was to delineate the educational and behavioral differences between learning disabled children with and without attention-deficit hyperactivity disorder (ADHD). A restrospective (TROHOC) multimeasure comparative design was employed. Parents' and teachers' questionnaires (ANSER system) pertaining to attention-activity, associated behaviors, and scholastic achievements were compared. Parents' questionnaires failed to distinguish between the two groups. Teachers' questionnaires were significantly more sensitive. Significant correlations between educational achievements and attention-activity and associated behaviors scores among children with learning disabilities were evident, no such correlations were found in the group with learning disability with ADHD. The factor analysis identified different educational and behavioral aggregates with language related difficulties and externalizing behaviors more typically aggregated in the learning disabled group with ADHD and recall deficit and internalizing/neurotic behaviors in the group with learning disability only. ADHD appears to be an associated comorbidity and not necessarily a specific learning deficit. However, children with learning disability with ADHD possibly have a different underlying neurocognitive pattern than their peers with learning disabilities only.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Language deficit with attention-deficit disorder: a prevalent comorbidity.

The aim of this study was to delineate the prevalence and behavioral patterns of children with attention-deficit and language problems as compared to children with attention-deficit hyperactivity disorder (ADHD) only. Out of a cohort of 3208 children 6 to 11 years old, 5.2% were identified as having a primary ADHD. A teacher's behavioral questionnaire, pediatric interview and assessment, IQ, attention tests, and language evaluation were employed. A 45% rate of language problems was identified. This comorbidity is more prevalent among girls (P = .02). Sequencing and short-term memory were significantly related to attention-deficit and language problems, but the attention scores were not. Language performance was the best predictor of group assignment and was superior to IQ in that regard. Correlation analysis revealed a different behavioral pattern for the two groups. It appears that a significant proportion of children with ADHD have a language comorbidity not reflected by IQ assessments; therefore, language tests should be considered as part of their routine assessment. Children with attention-deficit and language problems appear to have a different neurocognitive pattern underlying their problems as compared with their peers with ADHD only.

Attention Deficit Disorder with Hyperactivity↗
PubMed1998

Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; OMIM *240300, also called APS 1,) is a rare autosomal recessive disorder that is more frequent in certain isolated populations. It is generally characterized by two of the three major clinical symptoms that may be present, Addison's disease and/or hypoparathyroidism and/or chronic mucocutaneous candidiasis. Patients may also have a number of other clinical symptoms including chronic gastritis, gonadal failure, and rarely, autoimmune thyroid disease and insulin-dependent diabetes mellitus. We and others have recently identified the gene for APECED, which we termed AIRE (for autoimmune regulator). AIRE is expressed in thymus, lymph nodes, and fetal liver and encodes a protein containing motifs suggestive of a transcriptional regulator, including two zinc finger motifs (PHD finger), a proline-rich region, and three LXXLL motifs. Six mutations, in cluding R257X, the predominant Finnish APECED allele, have been defined. R257X was also observed in non-Finnish APECED patients occurring on different chromosomal haplotypes suggesting different mutational origins. Here we present mutation analyses in an extended series of patients, mainly of Northern Italian origin. We have detected 12 polymorphisms, including one amino acid substitution, and two additional mutations, R203X and X546C, in addition to the previously described mutations, R257X, 1096-1097insCCTG, and a 13-bp deletion (1094-1106del). R257X was also the common mutation in the Northern Italian patients (10 of 18 alleles), and 1094-1106del accounted for 5 of 18 Northern Italian alleles. Both R257X and 1094-1106del were both observed in patients of four different geo-ethnic origins, and both were associated with multiple different haplotypes using closely flanking polymorphic markers showing likely multiple mutation events (six and four, respectively). The identification of common AIRE mutations in different APECED patient groups will facilitate its genetic diagnosis. In addition, the polymorphisms presented provide the tools for investigation of the involvement of AIRE in other autoimmune diseases, particularly those affecting the endocrine system.

Female↗
PubMed1998

Alternatives to fundholding.

The new Labour government in the United Kingdom is proposing to adapt the reforms begun by the last Thatcher government. In particular, it is proposing to abolish the most controversial element--general practitioner (GP) fundholding. It is looking for alternatives. The study reported here followed and evaluated several such schemes. While fundholders use their purchasing power directly to force change by threatening "exit" to another provider, other GPs have evolved ways of influencing decisions--enhancing their "voice." The authors develop a theory to predict the conditions favoring the relative success of exit and voice strategies in health purchasing, and describe alternative GP-based purchasing schemes and the reasons they evolved in six sample districts. In four of these districts and eight practices in each, fundholding and non-fundholding GPs were then asked to describe their intentions and the outcomes of the purchasing process in which they had participated. Four specialties were taken as examples. The authors compare the relative success of fundholders and non-fundholders in achieving their objectives.

Attitude of Health Personnel↗
PubMed1998

Obliterative central bronchitis due to mineral dust in patients with pneumoconiosis.

OBJECTIVE: We studied at autopsy a distinctive obliterative bronchitis in three persons with pneumoconiosis and hilar node fibrosis. METHODS: Lungs were evaluated macroscopically, microscopically, and with energy-dispersive spectroscopy. RESULTS: Chest roentgenogram demonstrated right middle lobe syndrome in one patient; bronchostenosis was seen at bronchoscopy in another. The stenotic sites were in perihilar bronchi and showed an upper lobe predominance. Fibrosis with silicotic nodules involved the bronchus, peribronchial tissue, and adjacent lymph nodes. Simple coalworkers' pneumoconiosis was observed in two patients; the third had complicated, mixed dust fibrosis. CONCLUSION: Obliterative bronchitis represents an unusual fibrotic response to free crystalline silica. The process may occur simultaneously in the adjacent lymph node and the bronchial wall; however, it need not be associated with complicated pneumoconiosis. Clinically, obliterative bronchitis may masquerade as bronchogenic carcinoma.

Aged↗
PubMed1998

Transfusion practices in infants receiving assisted ventilation.

Controversies about medical practices usually arise from lack of definitive scientific studies. In the presence of continuing controversy about the appropriate hemoglobin level for ventilated (or nonventilated) infants, we can attempt to derive as much useful information as possible. In this article, the authors focus on four subjects: the physiologic role of red cells, the clinical effects of anemia and the proposed clinical benefit of red cell transfusions in preterm infants, the risks associated with transfusions, and the use of recombinant erythropoietin as an alternative to transfusion therapy.

Anemia, Neonatal↗
PubMed1998

Endocrine late effects in children who underwent bone marrow transplantation: review.

With the increasing use and success of BMT, larger numbers of children survive transplantation. Still, cancer treatment in children causes damage to the endocrine glands, often inducing growth deficiency, pubertal delay and thyroid dysfunction. This paper will deal with some of the most common endocrine disorders related to BMT in the pediatric population. Irradiation is the major contributor for growth impairment after BMT, acting through lesion to epiphyseal growth-plate, gonadal damage with delayed or precocious puberty, hypothyroidism, and growth hormone insufficiency. Gonadal dysfunction can be induced both by a direct injury to the gonads (irradiation, gonadotoxic agents) causing primary hypergonadotropic-hypogonadism, and with less frequency, by neuroendocrine injury to the hypothalamo-pituitary axis causing hypogonadotropic-hypogonadism. It seems that both doses of chemotherapy and of irradiation used by different regimens, fractionation of irradiation, and age at the time of BMT are the most important factors when we deal with toxic endocrine late-effects in long term survivors. In order to improve the quality of life of each single patient who receive BMT, and without inflicting the success-rate of this procedure, we recommend a life-long surveillance to prevent or to treat symptoms and disorders caused by hormone deficiencies, and we also advocate for a multidisciplinary team-approach that includes an endocrinologist consultant.

Bone Marrow Transplantation↗
PubMed1998

A subset of metastatic human colon cancers expresses elevated levels of transforming growth factor beta1.

Although transforming growth factor (TGF)-beta1 is a potent growth inhibitor of normal epithelial cells including colonocytes, TGF-beta1 has also been implicated as an enhancer of colon cancer metastasis. Decreasing TGF-beta1 protein levels in the metastatic U9 colon cancer cell line by antisense methodology decreased both U9 cell metastasis to the liver and s.c. tumor formation in a nude mouse system, and the tumors that did arise had regained TGF-beta1 expression (F. Huang et al, Cell Growth Differ., 6: 1635-1642, 1995). In addition, in a clinical immunohistochemistry study, colon cancers with elevated TGF-beta1 protein levels were found to be 18 times more likely to recur as distant metastases than colon cancers expressing low TGF-beta1 levels, after resection of the primary tumor (E. Friedman et al, Cancer Epidemiol. Biomark. Prev., 4:549-554, 1995). Because both studies implicated TGF-beta1 in colon cancer metastasis, we wished to know whether a selection bias for TGF-beta1 was maintained in metastatic cells or was only a property of the primary site tumors that were likely to metastasize. TGF-beta1 levels were measured using two different antibodies in paired primary site cancers and their metastases by immunohistochemistry and, in selected cases, by Western blot analysis. In 16 of 21 cases (76%) with antibody G and 23 of 31 cases (74%) with antibody P, higher expression of TGF-beta1 was found in colon cancer cells invading local lymph nodes compared with primary site colon cancer cells, or (2 and 6 cases, respectively) high TGF-beta1 expression in the primary site cancer was maintained in invasive cells. Analysis by Western blotting using both antibodies also demonstrated that higher levels of TGF-beta1 protein were found in metastases compared with the primary site tumor or normal tissue. Additional cases of paired primary site colon cancer, local lymph node metastases, and cancer cells metastasizing to distant sites were examined. In six of eight such cases (75%), TGF-beta1 levels were increased in both invasive cell populations compared with the primary site cancer (five cases), or high levels in the primary site cancer were maintained in the metastatic cells (one case). These data suggest that TGF-beta1 plays a role in promoting colon cancer metastasis throughout the metastatic process in roughly 75% of cases. TGF-beta1 may increase metastasis by paracrine mechanisms, such as suppression of local immune response or increased angiogenesis, as was seen with the U9 cell line. In those cancers with nonmutated TGF-beta receptors and nonmutated smad proteins like U9 cells, TGF-beta1 could also act in an autocrine manner to increase invasion by increasing cell motility (Hsu et al., Cell Growth Differ., 5: 267-275, 1994).

Blotting, Western↗
PubMed1998

[Effects of high sodium intake on ventricular remodeling in mice].

BACKGROUND: Despite extensive research, controversy still exists regarding the role of dietary sodium intake on hypertension and left ventricular (LV) hypertrophy. Echocardiography is a powerful tool to assess LV hypertrophy and recent technical developments allow now its use in small animals. METHODS: We examined the effect of high sodium intake on LV geometry using echocardiography in mice. Three groups of Swiss mice were submitted, for 8 weeks, to different salt diets (0.6, 2 and 4% NaCl; n = 12, n = 8 and n = 12 respectively). LV end-diastolic (ED) septal and posterior wall thicknesses, LV ED diameter were measured at baseline, 4 and 8 weeks. RESULTS: At baseline, heart rate, LV ED septal and posterior wall thicknesses and LV ED diameter were similar between groups. At 8 weeks, for similar heart rate, LV ED posterior wall thickness were not different (0.6%: 0.64 +/- 0.01, 2%: 0.62 +/- 0.08 and 4%: 0.67 +/- 0.03 mm respectively) but LV septal wall thickness ass increased in a salt diet dependent manner (0.6%: 0.63 +/- 0.01, 2%: 0.75 +/- 0.01, 4%: 0.80 +/- 0.02 mm, p < 0.01). This increase was correlated with urinary sodium excretion (r = 0.84, p < 0.01) but occurred in the absence of change in arterial pressure (tail-cuff plethysmography; 0.6%: 135 +/- 6.2%: 127 +/- 4 and 4%: 139 +/- 9 mmHg respectively). The in-vivo interventricular septal remodeling was confirmed in perfused fixed preparations of hearts. CONCLUSION: Echocardiography allows precise measurements of regional LV wall dimensions in mice, and high sodium intake, in the absence of hypertension, induces interventricular septal remodeling.

Animals↗
PubMed1998

[Recommendations of the French Society of Cardiology for the training of echocardiographers and performing echocardiograms].

The considerable advances achieved in the field of echocardiography have made this investigation an essential diagnostic tool. Under the auspices of the French Society of Cardiology, the Working group on Echocardiography publishes its practical recommendations for optimising the training of echocardiographers (theoretical instruction and practical courses) and for performing echocardiography (understanding the clinical problem, referral to previous examinations, necessary recordings and measurements, and appropriate equipment). In the future, these recommendations should be updated to take into account continuing technical improvements and changes in methods of studying cardiac disease by echocardiography.

Cardiology↗