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Biomedical subjects

A Baker

Publications and source records attributed to A Baker.

At least 109 records · Page 6Linked to original sources

Stabilization of cationic liposome-plasmid DNA complexes by polyamines and poly(ethylene glycol)-phospholipid conjugates for efficient in vivo gene delivery.

Stable complexes of cationic liposomes with plasmid DNA were prepared by (1) including a small amount of poly(ethylene glycol)-phospholipid conjugate or (2) condensing the DNA with polyamines prior to the formation of liposome-plasmid complexes. These preparations were stable for months at 4 degrees C and gave reproducible high transfection activity for in vivo gene delivery after intravenous injection in mice. Under these conditions, the expression of marker gene (luciferase) was primarily in the lungs (reaching values up to 3 ng expression per mg tissue protein), but also in other tissues to a lesser extent. Non-stabilized formulations lost all their transfection activity in 4 days. In these formulations cholesterol, not dioleoylphosphatidylethanolamine, was the helper lipid effective for sustaining high transfection activity in vivo. These new developments in formulation technology should enhance the potential for liposome-mediated gene therapy.

Animals↗

Hepatic artery resistance index can predict early death in children with biliary atresia.

Hepatic artery resistance index has been measured by ultrasonography Doppler and has been found to predict rapid deterioration and death in children with biliary atresia. Clinical, biochemical, ultrasonographic, and outcome data were collected prospectively and retrieved on 32 patients with resistance index of > or = 1.0 (group A). These were compared with the same data for 32 age- and sex-matched patients with biliary atresia and a resistance index of < 1.0 (group B). Group A was found to have significantly worse liver function tests than group B. In group A, all patients died (n = 11) or underwent transplantation (n = 21; of whom 4 died) compared with only 2 patients who died in group B and 4 patients who underwent transplantation without fatality. Survival at 2 years was 52% in group A v 94% in group B. It is suggested that regular ultrasonography Doppler examination in patients with biliary atresia can detect a group with a resistance index of > 1.0 who have a very high risk of early mortality. Such patients require early evaluation and listing for transplantation. Those listed for liver transplantation on other grounds require ultrasonography examinations every 2 to 3 months with immediate upgrading of the priority of those patients found to have a resistance index of > or = 1.0.

Actuarial Analysis↗

Clinical outcome of cryopreserved human pronuclear stage embryos resulting from intracytoplasmic sperm injection.

OBJECTIVE: To compare the survival rate and pregnancy rate (PR) of embryos from intracytoplasmic sperm injection (ICSI) or conventional IVF, which were cryopreserved at the pronuclear stage in cycles where fresh transfer was deferred. DESIGN: Comparative observational study. SETTING: University-associated IVF center. PATIENT(S): Ninety-nine patients who deferred ET and had all their embryos cryopreserved at the pronuclear stage after 153 oocyte retrievals. Thirty-nine patients had their oocytes inseminated by ICSI and 60 patients had conventional IVF insemination. INTERVENTION(S): All embryos were frozen-thawed at the two pronuclear stage and allowed to cleave for 2 days before transfer. MAIN OUTCOME MEASURE(S): Survival rate (morphologically intact after thaw), cleavage rate (cleaved by time of transfer), and the clinical PR after frozen ET. RESULT(S): In the ICSI group, 205 embryos were thawed for use in 57 frozen ETs; in the IVF group, there were 527 embryos thawed for use in 149 frozen ETs. There was no significant difference in any of the outcome measures by insemination method: survival rates (ICSI, 93.2%; IVF, 94.8%); cleavage rates (ICSI, 95.2%; IVF, 94.7%), and clinical PR (ICSI, 14.0%; IVF, 17.4%). CONCLUSION(S): Pronuclear embryos resulting from ICSI can be cryopreserved successfully, thawed, and the survival rate and PR are comparable to conventional IVF.

Adult↗

Hepatic transplantation in children under 3 months of age: a single centre's experience.

Liver transplantation in neonates represents a major medical and technical challenge particularly in babies weighing less than 5 kg. The authors report the experience of 10 liver transplants in 9 babies (6 boys and 3 girls), mean age, 6 weeks (range, 2 to 11); median weight, 3.7 kg (range, 2.4 to 5). All had fulminant hepatic failure caused by neonatal haemochromatosis (n = 3), non-A non-B hepatitis (n = 3), total parenteral nutrition induced (n = 1), hepatitis B (n = 1), and hepatic haemangio-endothelioma (n = 1). One child underwent retransplantation for hepatic artery thrombosis. Immunosuppression was by Cyclosporine A-based triple therapy in all cases. All received a reduced size graft consisting of left lobe (n = 1), left lateral segment (n = 6) and monosegment III (n = 3). In nine cases the donor hepatic artery was anastomosed to an iliac artery conduit from the infrarenal aorta, and a Roux loop was used for bile duct reconstruction. Primary abdominal wound closure was possible in six patients, skin closure alone in one, and a silastic patch was used in three. Complications included infection (n = 5), bowel perforation (n = 2), diaphragmatic perforation (n = 2), bile leak (n = 1), hepatic artery thrombosis (n = 1), and portal vein thrombosis (n = 1). None of the babies experienced acute rejection. Currently five of the nine recipients are alive with good graft function at a mean follow-up of 22 months (range, 5 to 58). Of the four deaths, two were related to infection (one in combination with portal vein thrombosis), one to multiorgan failure and fluid overload, and one to early graft dysfunction and sepsis after undergoing retransplantation for hepatic artery thrombosis. From our experience liver transplantation offers a promising option for the treatment of severe liver disease in children less than 3 months old.

Age Factors↗

Sleep disruption and mood changes associated with menopause.

This study examined the sleep and mood differences between premenopausal and perimenopausal women matched for age and sociodemographic variables. Wrist actigraphy, Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), a sleep questionnaire, and responses to a sleep diary were recorded for a period of 1 week. It was found that the sleep disruption of perimenopausal subjects was significantly greater than that of the premenopausal group (p < 0.05). Overall, the perimenopausal group demonstrated a significant increase in sleep disruption and mood alterations when compared with the premenopausal group. Actigraphic data showed that perimenopausal subjects experienced longer and more numerous arousals resulting in significantly less sleep (p < 0.05). In addition, perimenopausal subjects scored significantly higher (p < 0.05) on the STAI and significantly lower on the Vigor subscale of the POMS (p < 0.01) than premenopausal subjects. Correlational analyses indicated that sleep and mood changes were significantly related in the perimenopausal group, but not in the premenopausal group. Taken together, these results suggest that the mood changes experienced by the perimenopausal group may be mediated by sleep disruption.

Adult↗

Allelic loss of the FMS gene in acute myeloid leukaemia.

The FMS proto-oncogene encodes for the colony stimulating factor-1 receptor expressed on monocytes and B lymphocytes within the peripheral blood system. Allelic loss of the FMS gene occurs in patients with refractory anaemia and the 5q- syndrome associated with the myelodysplastic syndromes. To determine the frequency of FMS gene loss in patients with myeloid malignancy, 50 DNA samples from patients with acute myeloid leukaemia (AML) and 30 samples from haematologically normal samples were analysed using a quantitative Southern blotting technique. Allelic loss of one allele (hemizygous) was detected in five of 18 samples of AM-M4 and eight of 27 samples of AML M1, M2 and M3. In addition, loss of both FMS alleles (homozygous) was demonstrated in three of 18 samples of AML M4 and 0127 samples of AML M1, M2 and M3. One patient with AML M5 and one with AML M6 were assessed although no allelic loss of FMS was detected. Three samples from patients with secondary AML were also analysed and hemizygous loss was detected in one case. Homozygous or hemizygous loss of FMS was not detected in any of 30 DNA samples isolated from haematologically normal individuals. These data indicate that loss of the FMS gene is common in AML, with an increased frequency in those patients with AML subtype M4.

Aged↗

Selective activation of the external oblique musculature during axial torque production.

OBJECTIVE: To investigate whether different geographical regions of the external oblique musculature can activate at different levels and, if they do, to quantify the magnitude of these differences as a function of postural parameters during twisting exertions. DESIGN: Repeated measures design using electromyography on healthy subjects. BACKGROUND: The majority of the models currently used to assess spinal loading have represented the trunk musculature using single force vectors connecting a muscle's point of origin to its point of insertion. However, for muscles with large areas of origin and/or insertion (such as the external obliques), this single vector modelling approach misrepresents the multiple vector reality which, in turn, underestimates the complex loads these muscles can develop. METHODS: Nine subjects performed sub-maximal isometric axial twisting exertions (20, 40 and 60% of maximum voluntary contraction) while assuming six different postures defined by three levels of axial rotation (-20 degrees, 0 degrees and 20 degrees ) and two levels of sagittal flexion (0 degrees and 20 degrees ). As the subjects performed these isometric exertions, the integrated electromyographic activity was sampled using surface electrodes at five different locations over the right and the left external oblique muscles. RESULTS: The results showed significant (p<0.05) regional differences in the activation profiles and these activation profiles changed as a function of trunk posture. CONCLUSIONS: The external oblique musculature is capable of differential activation and the activation profiles of the different regions are affected by the posture of the torso. RELEVANCE: These findings suggest that the external oblique muscle is capable of selective activation of different regions along its cross-section and should, therefore, be modelled using multiple vectors. The result can have a direct bearing on the calculated spine loading, especially lateral and anterior/posterior shear forces.

Journal Article↗

Isolation of a cDNA encoding an Arabidopsis galactokinase by functional expression in yeast.

A cDNA clone encoding Arabidopsis thaliana galactokinase was fortuitously isolated during the course of a screen for plant homologues of a Saccharomyces cerevisiae peroxisome assembly gene, PAS9. Clones were sought which restored the ability of pas9 cells to grow on oleate as a sole carbon source, as oleate metabolism requires peroxisomal beta-oxidation and therefore functional peroxisomes. Subsequent experiments showed that high level expression of the galactokinase cDNA did not complement the peroxisomal assembly defect, but instead permitted the cells to grow on agar plates in the absence of an external carbon source. Agar plates were shown to contain a small amount of galactose released from the agar as a result of autoclaving. The galactokinase clone was shown to be functional, as it could complement a S. cerevisiae galactokinase mutant. Galactokinase is a single copy gene in Arabidopsis, which has been designated AGK1, and is expressed in all the major organs of the plant.

Amino Acid Sequence↗

Polyethylenimine (PEI) is a simple, inexpensive and effective reagent for condensing and linking plasmid DNA to adenovirus for gene delivery.

A simple and inexpensive method of condensing and linking plasmid DNA to carrier adenovirus particles is described. The synthetic polycation polyethylenimine is used to condense plasmid DNA into positively charged 100 nm complexes. These PEI-DNA complexes are then bound to adenovirus particles through charge interactions with negative domains on the viral hexon. The resulting transfection complexes deliver plasmid DNA to cells by the adenovirus infectious route without interference from virus gene expression because psoralen-inactivated virus is employed. The PEI-DNA-adenovirus complexes display DNA delivery comparable to more sophisticated DNA virus complexes employing streptavidin/biotin linkage, but require no special reagents and are much easier to prepare.

Adenoviridae↗

A United States multicentre trial of dual and proton pump inhibitor-based triple therapies for Helicobacter pylori.

BACKGROUND: One-week proton pump inhibitor-based triple therapies are very popular in the US despite limited US data documenting efficacy. We assessed 1-week proton pump inhibitor triple therapies for Helicobacter pylori, and compared them to dual antibiotic therapies (to assess benefit of omeprazole) and to omeprazole-amoxycillin (to assess benefit of clarithromycin) in a large, randomized, US multicentre study. METHODS: Healthy subjects who were H. pylori-positive by rapid serological test and 13C-urea breath test were randomly assigned to (i) omeprazole (O) 20 mg b.d. + amoxycillin (A) 1 g t.d.s. for 14 days (OA); (ii) A 1 g b.d. + clarithromycin (C) 500 mg b.d. for 7 days (AC); (iii) C 250 mg b.d. + metronidazole (M) 500 mg b.d. for 7 days (CM); (iv) O 20 mg b.d. + C 250 mg b.d. + M 500 mg b.d. for 7 days (MOC); or (v) O 20 mg b.d. + C 500 mg b.d. + A 1 g b.d. for 7 days (OAC). Repeat breath tests were done at 6 weeks to assess H. pylori status. RESULTS: Three hundred and two H. pylori-positive subjects at 25 centres received medication. Intention-to-treat cure rate was significantly higher for OAC (82%) than for MOC (67%), CM (59%), AC (18%) or OA (58%), Per-protocol cure rates were 85% for OAC and 75% for MOC. Discontinuation of therapy due to a side-effect occurred in 0-3% of each study group. CONCLUSIONS: One-week twice-daily triple therapy with omeprazole, amoxycillin and clarithromycin provides the best rate of eradication of the five regimens studied. However, treatment in the US for 7 days may be unable to achieve eradication rates of > or = 90% with proton pump inhibitor-based triple therapy.

Adult↗

Identification of a novel antiapoptotic protein, GAM-1, encoded by the CELO adenovirus.

We have developed a simple screening method to identify genes that mimic bcl-2 or adenovirus E1B 19K in enhancing cell survival after transfection and have used this method to identify such a gene in the avian adenovirus CELO. The gene encodes a novel 30-kDa nuclear protein, which we have named GAM-1, that functions comparably to Bcl-2 and adenovirus E1B 19K in blocking apoptosis. However, GAM-1 has no sequence homology to Bcl-2, E1B 19K, or any other known antiapoptotic proteins and thus defines a novel antiapoptotic function.

Adenovirus E1B Proteins↗

Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype.

The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.

Aged↗

Liver transplantation for extra hepatic biliary atresia.

Kasai portoenterostomy has transformed the prognosis for children with Extra Hepatic Biliary Atresia (EHBA). However, for children developing end stage liver disease following portoenterostomy, liver transplantation (OLT) is the treatment of choice. Between February 1989 and March 1996, 64 children with EHBA underwent 79 transplants (26 males, 38 females; median age 2.2 years, range 5 months-17 years; median weight 11.4 kg, range 5-65 kg). Of these, 58 (85%) had undergone previous portoenterostomy. Nineteen patients (30%) had gastrointestinal bleeding prior to OLT assessment. Mean serum bilirubin was 229 mumol/liter (range 11-801 muml/liter). Four children had associated polysplenia syndrome. Of the 79 transplants, 30 received whole and 41 reduced-size cadaveric grafts and 9 living related grafts. Eleven patients (17%) died, nine within one month of surgery. Thirteen patients were retransplanted once and one twice. There were 16 vascular complications (10 hepatic artery thrombosis, 3 portal vein thrombosis, 3 venous outflow obstruction) and 10 biliary complications (4 anastomotic leaks, 6 strictures). Ten patients (16%) had bowel perforation following the transplant. The 5 year actuarial patient and graft survival for this group is 84% and 69% respectively with normal physical and mental development in the majority. OLT provides satisfactory treatment for children with EHBA with end stage liver disease with long term survival in the majority.

Adolescent↗

11 beta-Hydroxysteroid dehydrogenase enzyme activity in granulosa cells derived from ovarian follicles of in vitro fertilization patients.

11 beta-Hydroxysteroid dehydrogenase (HSD) activity was measured in freshly frozen granulosa cells isolated from follicles of twenty-one infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET). A total of 213 follicles were analyzed for 11 beta-HSD activity. Both nicotinamide-adenine dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP) dependent 11 beta-dehydrogenase activities were measured in granulosa cells. The activity in reductive direction (11-oxoreductase activity) was not measurable either with NADH or NADPH as cofactors. NAD- and NADP-dependent dehydrogenase activities are in comparable levels at 100 nmol/l and 1 mumol/l corticosteroid concentrations. For comparing enzyme activities of individual follicles, significant enzyme activity was considered to be a level of > 2 nmol/l/min/mg. 41.3% of the follicles demonstrated enzyme activity, 58.7% did not. The mean 11 beta-dehydrogenase (11 beta-DH) activity was calculated for each patient. Those patients with levels > 2 nmol/l/min/mg were considered enzyme positive; those with mean levels < 2 nmol/l/min/mg were considered negative. No significant association was noted between follicle size, oocyte maturity or fertilization rates and 11 beta-DH activity. This study noted the presence of 11 beta-DH activity in granulosa cells, however, no association with oocyte maturity and fertilization was found.

11-beta-Hydroxysteroid Dehydrogenases↗

Selenium and the thioredoxin redox system: effects on cell growth and death.

Thioredoxin is a redox protein found overexpressed in some human tumors. Thioredoxin is secreted by tumor cells and enhances the sensitivity of the cancer cells to other growth factors. Redox activity is essential for stimulation of cell growth by thioredoxin. Cells transfected with thioredoxin cDNA show increased tumor growth and decreased apoptosis in vivo and decreased sensitivity to apoptosis induced by a variety of agents both in vitro and in vivo. Cells transfected with a redox-inactive mutant thioredoxin show inhibited tumor growth in vivo. Dietary selenium has been shown to prevent some forms of human cancer. Selenocysteine is an essential component of thioredoxin reductase, the flavoenzyme that is responsible for the reduction of thioredoxin. Selenium added to the culture medium increases thioredoxin reductase activity due to an increase in thioredoxin reductase protein but mostly due to an increase in the specific activity of the enzyme. Some diaryl chalcogenide (selenium and tellurium) compounds have been studied as inhibitors of thioredoxin reductase. The most active were diaryl tellurium compounds, which were noncompetitive inhibitors of thioredoxin reductase with Ki values of 2-10 microM. Several of the compounds inhibited cancer cell colony formation in vitro with IC50s as low as 2 microM.

Apoptosis↗