High densities of cold atoms in a dark spontaneous-force optical trap.
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Journal Article↗
Biomedical subjects
A Martin
Publications and source records attributed to A Martin.
Lack of evidence for Huntington's disease-like cognitive dysfunction in obsessive-compulsive disorder.
Cognitive deficits in patients with structural lesions of the basal ganglia (e.g., Huntington's disease) commonly include slowed processing, reduced verbal fluency, difficulty switching set, impaired egocentric spatial ability, poor recall, and impaired acquisition of motor skills. The goal of this study was to determine if patients with obsessive-compulsive disorder (OCD) would have a similar pattern of cognitive dysfunction. A battery of neuropsychological tests, including reaction time-based measures of cognitive processing speed and a test of procedural, motor-skill learning, was administered to 17 unmedicated OCD patients and 16 age-and education-matched normal controls. Eleven individuals with trichotillomania, matched with the OCD patients on age, education, age at symptom onset, depression, and anxiety were also tested. Contrary to expectation, neither the OCD nor trichotillomania patients were impaired on any of the measures in the battery. The essentially normal performance by these patients suggests that the brain regions responsible for cognitive dysfunction in patients with Huntington's disease may differ from those associated with OCD.
Adolescent↗
Cholesterol feeding induces hypertriglyceridaemia in hamsters and increases the activity of the Mg(2+)-dependent phosphatidate phosphohydrolase in the liver.
(1) Feeding increased cholesterol to hamsters resulted in a dose-dependent increase in cholesterol and triacylglycerol in very-low-density lipoprotein (VLDL), in serum non-esterified fatty acids and in the activity of the Mg(2+)-dependent phosphatidate phosphohydrolase in liver. (2) The effects of increasing dietary cholesterol by 0.12% (w/w) in addition to feeding fat (14%, w/w) were dependent upon the nature of the fat. Lard in the presence of 0.12% (w/w) cholesterol increased serum triacylglycerols as did olive oil. By contrast, sunflower oil did not cause a significant change in serum triacylglycerol concentrations. (3) There was a highly positive correlation between VLDL triacylglycerol and VLDL cholesterol concentrations suggesting that, at least in this model, there is a close relationship between hypertriglyceridaemia and hypercholesterolaemia.
Animals↗
What do gastroenterologists in Europe tell cancer patients?
This survey concerns the variation in attitudes among European gastroenterologists to truth telling in cases of cancer. Gastroenterologists in all parts of Europe were asked to consider a case of colonic cancer and to state what they would tell the patient and the patient's spouse. 260 replied. Gastroenterologists in northern Europe would usually reveal the diagnosis to both the patient and the patient's spouse, but some would inform only the spouse with the patient's permission. They would sometimes embellish the truth if the cancer had metastasised. Gastroenterologists in southern and eastern Europe would usually conceal the diagnosis from the patient, in many cases even when the patient asked to be told the truth. Most, however, would tell the spouse the full truth about both diagnosis and prognosis. The variation probably reflects differences in both doctors' attitudes and patients' expectations.
Attitude of Health Personnel↗
Screening for germ line p53 mutations in children with malignant tumors and a family history of cancer.
We have undertaken a routine investigation of the p53 status for all the children treated at our institution either affected by multiple tumors or whose family displays at least one second degree relative or less, affected by cancer before the age of 45 years. We report here on the first set of ten such families, eight of which were identified through a proband with sarcoma. p53 exons 5 to 8 have been sequenced following polymerase chain reaction amplification performed on DNA isolated from total blood. A missense mutation affecting codons 248, 273, and 282 was identified in three families. The mutation was inherited in these three families and was detected in unaffected members. In seven families no mutation was detected in exons 5 to 8.
Adolescent↗
Partial solubility parameters and solvatochromic parameters for predicting the solubility of single and multiple drugs in individual solvents.
A modification of the extended Hansen method is used for estimating the solubility of sulfadiazine and other organic drug molecules in a number of individual solvents ranging from nonpolar to highly polar. The equations obtained for each drug involve the partial solubility parameters of the solvents and allow the prediction of solubility of these drugs in a new solvent. Furthermore, a number of drugs (e.g., sulfadiazine, sulfamethoxypyridazine, naphthalene, and some benzoic acid derivatives) are combined in a single expression including the ideal solubility of the drugs and the partial solubility parameters of the solvents. The equation fits the solubilities of these drugs in a wide variety of solvents and may be used to predict the solubility of other sulfonamides and benzoic acid derivatives in semipolar and highly polar solvents. The solvatochromic parameter approach is also used in models for predicting the solubility of single drugs in individual solvents. It was tested with multiple solutes as was the partial solubility parameter approach. However, the latter approach is superior; the parameters of the solubility parameter method are all statistically significant for drugs tested individually or together in a single equation, a condition that is not obtained with the solvatochromic model.
Benzoates↗
A nondenaturing preparative gel electrophoresis system for the recovery of functional proteins. Application to the identification of an endogenous protein inhibitor of fucosyl-transferase activities.
Electroelution of protein bands resolved by nondenaturing polyacrylamide gel electrophoresis was performed to identify an endogenous protein inhibitor of fucosyltransferase activities, called fuctinin, through its biological activity. After electrophoresis protein bands were negatively stained with zinc acetate, indicating that this staining technique can be also applied to nondenaturing polyacrylamide gels. However, even under appropriate electroelution conditions, a strong fucosyl-transferase inhibitory activity was eluted from the polyacrylamide gel itself that impeded the measure of fuctinin activity. As an alternative to electroelution, collection of proteins resolved by nondenaturing polyacrylamide gel electrophoresis as they are electrophoresed off the end of the gel was assayed. In the commercially available preparative electrophoretic systems, an elution chamber is limited by a semipermeable membrane on which proteins were adsorbed in the low-ionic-strength buffer used in nondenaturing electrophoresis. We demonstrate that the simple and inexpensive electrofractionation system described by Shain et al. (Anal. Biochem. 200, 47-51, 1992) can be successfully applied under nondenaturing conditions to purify and identify fuctinin through its biological activity. However, caution must be taken in the design of the apparatus in order to avoid local heating and thermal denaturation of proteins. The utility of this nondenaturing preparative electrophoresis system for the study of functional proteins is also demonstrated by the recovery of enzymatic activities of alkaline phosphatase and beta-galactosidase.
Electrophoresis, Polyacrylamide Gel↗
Potential use of poliovirus as a vector.
The live attenuated Sabin strains of poliovirus have proven their efficacy at inducing a good humoral and secretory antibody response in humans. The extensive characterization of poliovirus neutralization antigenic sites and the atomic resolution of the three-dimensional structure of the viral capsid have enabled the use of the most stably attenuated poliovirus strain (the Sabin type 1 strain) as a vector for the presentation of short foreign antigenic domains in place of one of its own neutralization antigenic sites. The creation of such chimeras has been achieved by manipulating poliovirus infectious cDNA and transfecting the resulting chimeric cDNAs onto susceptible cell cultures. However, this epitope-presentation system has a limitation in terms of the sequence and size of the foreign domain that can be incorporated into the poliovirus capsid without disrupting virus viability. This has led to the construction of poliovirus hybrid genomes bearing insertions of longer heterologous sequences in place of part of the poliovirus structural genes. Upon transfection onto susceptible cells providing the poliovirus structural proteins in trans (e.g. cells previously infected with the Sabin 1 strain), stocks of encapsidated RNA replicons which expressed the foreign protein could be obtained. In addition, viable recombinant viruses bearing insertions of heterologous sequences at various places into the poliovirus genome without deleting poliovirus sequences have been reported. Potential applications of these chimeric and recombinant polioviruses in the engineering of new recombinant vaccines are discussed.
Animals↗
Comparison of 5 microplate colorimetric assays for in vitro cytotoxicity testing and cell proliferation assays.
This paper describes a critical comparative evaluation of 5 miniaturised colorimetric assays applicable to cytotoxicity testing of anti-tumour drugs (and other toxins) in vitro. Each assay shows a different linear range for optical density versus cell number, a different sensitivity to change in cell number and a different minimum detectable cell number; the values of these parameters vary with experimental conditions and with cell line used. All the methods gave good correlation with viable cell number (determined by colony forming efficiency) in toxicity assays after 3 or 4 days of treatment, but they underestimated cell death after 2 days. Toxicity levels for individual chemicals (in a standard 6-day assay) are similar for the different assays, irrespective of the mechanism of action of the chemical being tested. Two of the more recently developed assays (APNaOH and SRB) were found to be very sensitive under the conditions examined.
Antineoplastic Agents↗
The children of divorce parenting intervention: outcome evaluation of an empirically based program.
Examined efficacy of an empirically based intervention using 70 divorced mothers who participated in a 12-session program or a wait-list condition. The program targeted five putative mediators: quality of the mother-child relationship, discipline, negative divorce events, contact with fathers, and support from nonparental adults. Posttest comparisons showed higher quality mother-child relationships and discipline, fewer negative divorce events, and better mental health outcomes for program participants than controls. More positive program effects occurred for mothers' than children's reports of variables and for families with poorest initial levels of functioning. Analyses indicated that improvement in the mother-child relationship partially mediated the effects of the program on mental health.
Adaptation, Psychological↗
Liver transplantation in Italy and the scarcity of donors: causative factors and ethical considerations.
We analyze the current state of liver transplantation (OLTx) in Italy that in the last few years had reached approximately 150 OLTx per year for a population of 58 millions of inhabitants. The need for OLTx in Italy is high and mainly due to the incidence of post-hepatitis and post-alcoholic liver cirrhosis, which are the prevalent indication for OLTx. On the contrary the availability of donor organs in Italy is very low as compared with other European countries, and as a consequence the gap between need and performed OLTx is widening. The reasons for poor donations are multifactorial among which; lack of organization, insufficient ICU care beds, poor knowledge of health personnel. General attitudes of the society and brain death concepts are also involved as a recent survey has demonstrated. Under certain circumstances the patient who cannot be transplanted on time in Italy is allowed to seek for care abroad under the local government economical assistance. Finally some ethical considerations and the proposal for better education of both population and health care providers are advocated.
Adult↗
Longitudinal study of EEG and evoked potentials in neurologically asymptomatic HIV infected subjects.
Serial electroencephalograms (EEGs) and multimodality evoked potentials (EPs) were performed along with neurological and neuropsychological evaluation, cerebrospinal fluid assessment and magnetic resonance imaging at 6 month intervals in 73 neurologically asymptomatic HIV infected subjects. The results were compared with 50 age- and sex-matched controls. EEG was abnormal in 2 subjects (3%) initially and was abnormal in 7 (9%) subjects by the last examination. EEG abnormality (diffuse slowing) correlated significantly with slowed reaction time in neuropsychological testing (P < 0.05). VEP and BAEP provided low yields of 1.3% and 4% respectively. SEP was abnormal in 7 (9%) of the subjects initially and in 10 (13%) subjects by the last testing, with 80% of the abnormalities seen on the posterior tibial study. In 3 subjects, initial SEP abnormalities predicted later development of myelopathy and peripheral neuropathy. Event-related auditory evoked potentials were performed in 39 subjects. They were abnormal in 5 subjects initially (12%) and in 6 subjects (15%) by the last examination and more commonly in advanced stages of the illness with lower T4 counts. This data shows the evolution and association of electrophysiological abnormalities in early HIV infection and suggests a predictive value for SEP in HIV infected asymptomatic individuals.
Adult↗
Rearrangement of the N-myc oncogene in acute leukemias: a case report.
Rearrangements of the N-myc oncogene have not been described in the literature. The authors present a case of ANLL with the N-myc gene rearranged out of 16 ANLLs and 11 ALLs. While the proportion of the blast cells in the case reported was 85%, the rearranged gene gave a hybridization band which was less intense than that of the germline band, making it probable that this gene rearrangement is present in a leukemia subclone. The c-myc oncogene as well as Ig and TcR genes were in germline configurations. The presence of the rearranged N-myc in the reported case could imply an alternative mechanism of mutation of this oncogene in the pathogenesis of hematological malignancies.
Aged↗
Origin of Schwann cells in peripheral nerve allografts in the rat after withdrawal of cyclosporine.
The origin of Schwann cells in peripheral nerve allografts following rejection was determined by immunohistochemistry. Sciatic nerve allografts from ACI-RT1a rats were transplanted into Lewis-RT1l sciatic nerves using epineurial sutures. Isografts were taken from Lewis-RT1l rats. Cyclosporine (CsA) was administered subcutaneously daily, 5 mg/kg for 12 weeks, to the rats in each group. Allografts with CsA were sacrificed in groups at 12, 14, 16, 20, 24, and 36 weeks postoperatively during the rejection and recovery phase. Allografts and isografts without CsA were evaluated at 3, 6, 12, and 24 weeks. Nerves were frozen and cross sections immunohistochemically stained against Lewis rat HLA (RT1) and against Schwann cells (S-100 antigen). Allografts without CsA demonstrated minimal reaction to anti-Lewis compared to control isografts, which stained positively at all times. Schwann cells were not as well-stained in the allografts. Allografts with CsA showed reactivity to S-100 at 12 weeks, but minimal activity to Lewis antibody. Minimal reactivity to both S-100 and Lewis existed at 16 weeks, but increased gradually by 24 and 36 weeks. Therefore, Schwann cells from the recipient migrate into the graft and replace the Schwann cells from the donor following rejection.
Animals↗
A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin-structure infections.
An open, randomized, multicentre study was undertaken to compare a three-day regimen of azithromycin with a seven-day course of dicloxacillin or flucloxacillin in the treatment of 118 children (aged 2-12 years) with clinically diagnosed acute skin and skin-structure infections. Sixty patients received a single daily dose of azithromycin of 10 mg/kg for three days, whilst 58 received a cloxacillin ester: either dicloxacillin (n = 49) at a daily dose of 12.5-25 mg/kg (depending on severity of infection); or flucloxacillin (n = 9) at 250-2000 mg/day (depending on age). Both cloxacillin esters were administered in four divided doses for seven days. Clinical, safety and, where possible, bacteriological assessments were made before therapy and after 3 to 5 and 7 to 10 days of treatment. A successful clinical response (cure and improvement) was recorded in 57 of 59 (97%) of evaluable azithromycin patients, and in 57 of 58 (98%) of cloxacillin ester patients. Eradication of the key pathogens was 31 of 34 (91%) and 34 of 35 (97%) for Staphylococcus aureus, and 5 of 5 and 4 of 4 for Streptococcus pyogenes in the azithromycin and cloxacillin ester groups, respectively. Both medications were well tolerated, with mild to moderate side-effects (abdominal pain and vomiting) occurring in two patients in each group, and laboratory abnormalities (elevated eosinophil count) in one patient in each group. There were no withdrawals from therapy. The results of this study suggest that azithromycin is as effective and as well tolerated as a cloxacillin ester antibiotic in the treatment of children with acute skin and skin-structure infections.
Azithromycin↗
Modulation of alpha 1-adrenoceptors in rat left ventricle by ischaemia and acyl carnitines: protection by ranolazine.
Myocardial alpha 1-adrenoceptor number has been reported to increase during ischaemia in myocytes consequent to an increase in acyl carnitine levels. We investigated whether this phenomenon occurs in vivo and whether the novel antiischaemic agent ranolazine will protect against it. Thirty-minute occlusion of the left anterior descending coronary artery (LAD) in anaesthetised rats produced an approximate doubling of the left ventricular (LV) alpha 1-adrenoceptor population. The carnitine palmitoyl transferase 1 (CPT1) inhibitor sodium 2-[5-(4-chlorophenyl)-pentylene]oxiran-2-carboxylate (POCA 100 micrograms/kg) reduced this ischaemia-induced increase when administered intraperitoneally (i.p.) 15 min before ischaemia and abolished the increase when administered intravenously (i.v.). The CPT1 inhibitor sodium 2-tetradecyl oxirane carboxylate dihydrate (TGDA) (500 micrograms/kg) inhibited the upregulation when administered i.p. and significantly decreased alpha 1-adrenoceptor density when administered i.v.; however, this agent, unlike POCA, reduced [3H]-prazosin binding directly. The alpha 1-adrenoceptor antagonist prazosin (100 micrograms/kg i.v.) did not prevent the increase. Direct addition of palmitoyl carnitine (10 microM) to membranes from nonischaemic myocardium caused a doubling in alpha 1-adrenoceptor number, and this effect was selective for heart membranes as compared with cerebral cortex; beta-adrenoceptor number was not modified. Ranolazine (500 micrograms/kg) inhibited upregulation when administered 15 min i.v. before ischaemia or after 3-day twice-daily (b.i.d.) i.p. pretreatment. This drug did not inhibit CPT1 directly.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetanilides↗
Expression of adhesion molecules in allograft renal dysfunction. A distinct diagnostic pattern in rejection and cyclosporine nephrotoxicity.
We have studied in thirty renal biopsies (from 30 cadaver allograft patients) the expression of both LFA-1 and VLA-4 leukocyte adhesion receptors and their respective ICAM-1 and VCAM-1 endothelial cell ligands, during early allograft dysfunction (24 +/- 5 days after transplantation), reversed either by antirejection therapy (n = 14) or by reduction in CsA dose (n = 16). We have found that the levels of expression of the integrin VLA-4 and the activation signal AIM/CD69 (activation inducer molecule) on interstitial cells were significantly (P < 0.001) higher in rejection than in nephrotoxicity. A main differential expression pattern was observed for VCAM-1, the endothelial cell ligand of VLA-4. Interestingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody in rejection, as compared with a weak reactivity in endothelium and discrete staining pattern on tubules in nephrotoxicity. On the other hand, we found that the mean percentage of infiltrating cells bearing LFA-1 molecules and the intensity of ICAM-1 (a LFA-1 ligand) expression on endothelium were closely similar in both rejection and CsA nephrotoxicity. Nevertheless, a discrete significant (P < 0.05) "de novo" expression of ICAM-1 was present on tubular cells during rejection. Our results strongly suggest that in rejection the interstitial cell infiltrate seems to be facilitated by the contribution of both LFA-1/ICAM-1 and VLA-4/VCAM-1 cell adhesion mechanisms, and also that VLA-4/VCAM-1 leukocyte interaction does not play a role in cases with CsA nephrotoxicity. Furthermore, the differential expression patterns of VLA-4 and VCAM-1 molecules found between rejection and CsA nephrotoxicity could provide valuable immunohistochemical criteria in the diagnosis of allograft dysfunction.
Adult↗
Inaugural meeting of European network of therapeutics teachers.
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Education, Medical, Graduate↗