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Biomedical subjects

R Brenner

Publications and source records attributed to R Brenner.

At least 19 recordsLinked to original sources
PubMed2006

Spin-dependent quasiparticle transport in aluminum single-electron transistors.

We investigate the effect of Zeeman splitting on quasiparticle transport in normal-superconducting-normal (NSN) aluminum single-electron transistors (SETs). In the above-gap transport, the interplay of Coulomb blockade and Zeeman splitting leads to spin-dependence of the sequential tunneling. This creates regimes where either one or both spin species can tunnel onto or off the island. At lower biases, spin-dependence of the single quasiparticle state is studied, and operation of the device as a bipolar spin filter is suggested.

Journal Article↗
PubMed2005

Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease.

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. RESULTS: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. CONCLUSION: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.

Adult↗
PubMed2003

Progress in silicon-based quantum computing.

We review progress at the Australian Centre for Quantum Computer Technology towards the fabrication and demonstration of spin qubits and charge qubits based on phosphorus donor atoms embedded in intrinsic silicon. Fabrication is being pursued via two complementary pathways: a 'top-down' approach for near-term production of few-qubit demonstration devices and a 'bottom-up' approach for large-scale qubit arrays with sub-nanometre precision. The 'top-down' approach employs a low-energy (keV) ion beam to implant the phosphorus atoms. Single-atom control during implantation is achieved by monitoring on-chip detector electrodes, integrated within the device structure. In contrast, the 'bottom-up' approach uses scanning tunnelling microscope lithography and epitaxial silicon overgrowth to construct devices at an atomic scale. In both cases, surface electrodes control the qubit using voltage pulses, and dual single-electron transistors operating near the quantum limit provide fast read-out with spurious-signal rejection.

Journal Article↗
PubMed2002

Lipofection of rabbit chondrocytes and long lasting expression of a lacZ reporter system in alginate beads.

OBJECTIVE: Our aim was to investigate the maintenance of the transfection status of non-viral transfected chondrocytes in an alginate culture system. DESIGN: Chondrocytes harvested from rabbit knees were isolated by sequential digestion and cultivated in monolayer culture. At 60-70% cell density, chondrocytes were transfected with different transfection systems (FuGENE6, CaCl2, Lipofectin). A lac Z expression vector (pcDNA 3.1/Myc-His+ lacZ) was used as a reporter system. In order to improve transfection rates, hyaluronidase (4 U/ml) was used prior and during the transfection procedure. Thereafter, transfected cells were either kept in monolayer culture or embedded in alginate beads and kept in culture for up to the next 30 weeks. RESULTS: Transfection efficiency was maximal using FuGENE6TM/DNA at a ratio of 3:2 and hyaluronidase (4 U/ml). Transfection efficiency reached up to 40.8% (+/- 3.2%) after 36 h. In alginate beads lac Z positive cells declined to 8.5% +/- 3.3% after 4 weeks and to 4.6% +/- 3.2% after 12 weeks of culturing. After 30 weeks 3% of chondrocytes still expressed lac Z. In contrast, during culturing in monolayer, no lac Z expression was detectable after 4 weeks. Differentiation status of the chondrocytes was confirmed by histology and immunohistochemistry methods. CONCLUSIONS: After successful gene transfer to rabbit chondrocytes the alginate system made it possible to culture lipofected chondrocytes phenotypically stable. Genetically engineered chondrocytes express the lac Z reporter gene over a period of at least 30 weeks. This transfection and culture system provides a promising tool to further investigate the over-expression of growth factors and enzyme inhibitors.

Alginates↗
PubMed2001

Beta1-subunit of the Ca2+-activated K+ channel regulates contractile activity of mouse urinary bladder smooth muscle.

1. The large-conductance calcium-activated potassium (BK) channel plays an important role in controlling membrane potential and contractility of urinary bladder smooth muscle (UBSM). These channels are composed of a pore-forming alpha-subunit and an accessory, smooth muscle-specific, beta1-subunit. 2. Our aim was to determine the functional role of the beta1-subunit of the BK channel in controlling the contractions of UBSM by using BK channel beta1-subunit 'knock-out' (KO) mice. 3. The beta-galactosidase reporter (lacZ gene) was targeted to the beta1 locus, which provided the opportunity to examine the expression of the beta1-subunit in UBSM. Based on this approach, the beta1-subunit is highly expressed in UBSM. 4. BK channels lacking beta1-subunits have reduced activity, consistent with a shift in BK channel voltage/Ca2+ sensitivity. 5. Iberiotoxin, an inhibitor of BK channels, increased the amplitude and decreased the frequency of phasic contractions of UBSM strips from control mice. 6. The effects of the beta1-subunit deletion on contractions were similar to the effect of iberiotoxin on control mice. The UBSM strips from beta1-subunit KO mice had elevated phasic contraction amplitude and decreased frequency when compared to control UBSM strips. 7. Iberiotoxin increased the amplitude and frequency of phasic contractions, and UBSM tone of UBSM strips from beta1-subunit KO mice, suggesting that BK channels still regulate contractions in the absence of the beta1-subunit. 8. The results indicate that the beta1-subunit, by modulating BK channel activity, plays a significant role in the regulation of phasic contractions of the urinary bladder.

Animals↗
PubMed2001

Lateral recumbent head-down posture for epidural catheter insertion reduces intravascular injection.

PURPOSE: The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic. The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization performed in three different body positions. METHODS: The study was conducted in 900 (three groups of 300) obstetric patients undergoing continuous epidural analgesia during their labour and who were randomly allocated to three groups. Epidural catheterization was performed with patients in the sitting, lateral recumbent horizontal, or lateral recumbent head-down position. RESULTS: There was a lower incidence of vessel cannulation when this procedure was performed in the lateral recumbent head-down position (2%) than in the lateral recumbent horizontal (6%) and in the sitting position (10.7%). CONCLUSION: Adoption of the lateral recumbent head-down position for the performance of lumbar epidural blockade, in labour at term, reduces the incidence of lumbar epidural venous puncture.

Adolescent↗
PubMed2001

Use of olanzapine for elderly patients with psychotic disorders: a review.

The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.

Aged↗
PubMed2001

Recurrent mutations in the COL1A2 gene in patients with osteogenesis imperfecta.

A new recurrent point mutation in the COL1A2 gene was found in a patient with type III osteogenesis imperfecta (OI). A G-to-T transversion in nucleotide position 1121 leads to an amino acid substitution Gly238Cys. This is the first report on the most N-terminal cysteine substitution in COL1A2 reported so far. Until now, at this position, only serine substitutions were observed five times in unrelated patients showing a highly variable expression of OI. It is obvious that endogenic and/or exogenic modifiers are involved in this classical autosomal dominant (or rarely recessive) mendelian disorder. An apparent preferential substitution by cysteine and serine residues is discussed with reference to post-transcriptional or post-translational collagen assembly control.

Amino Acid Substitution↗
PubMed2001

Gene expression of stromelysin and aggrecan in osteoarthritic cartilage.

OBJECTIVE: To analyze cartilage gene expression of patients with osteoarthritis (OA) in correlation with radiographic and histological findings. MATERIALS AND METHODS: Twenty-one patients with OA of the knee admitted for total knee replacement were analyzed clinically and radiographically by the Kellgren and Lawrence system. During surgery, cartilage samples from the medial and lateral condyles and tibial plateaus were harvested separately. Specimens were analyzed histologically (Mankin score) and total RNA was extracted directly from cartilage tissue. Steady state levels of stromelysin (MMP-3), aggrecan (AGG) and the house-keeping gene beta-actin were measured using quantitative PCR. RESULTS: Histology of medial and lateral knee compartments corresponded to radiographic changes (Spearman correlation coefficient: r = 0.7 (p < 0.01)). There was a positive correlation between MMP-3 and AGG gene expression (r = 0.4; p < 0.01). We found considerable variation of expression levels of MMP-3 and AGG and no correlation of gene expression with histological or radiographic scoring. CONCLUSION: The positive correlation between AGG and MMP-3 suggests a common regulation of anabolic and catabolic metabolism. There was no simple dependency between gene expression and histological and radiological findings in cartilage.

Aged↗
PubMed2000

Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.

Small arteries exhibit tone, a partially contracted state that is an important determinant of blood pressure. In arterial smooth muscle cells, intracellular calcium paradoxically controls both contraction and relaxation. The mechanisms by which calcium can differentially regulate diverse physiological responses within a single cell remain unresolved. Calcium-dependent relaxation is mediated by local calcium release from the sarcoplasmic reticulum. These 'calcium sparks' activate calcium-dependent potassium (BK) channels comprised of alpha and beta1 subunits. Here we show that targeted deletion of the gene for the beta1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The beta1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation.

Animals↗
PubMed2000

Molecular separation of two behavioral phenotypes by a mutation affecting the promoters of a Ca-activated K channel.

The Drosophila slowpoke gene encodes a BK-type calcium-activated potassium channel. Null mutations in slowpoke perturb the signaling properties of neurons and muscles and cause behavioral defects. The animals fly very poorly compared with wild-type strains and, after exposure to a bright but cool light or a heat pulse, exhibit a "sticky-feet" phenotype. Expression of slowpoke arises from five transcriptional promoters that express the gene in neural, muscle, and epithelial tissues. A chromosomal deletion (ash2(18)) has been identified that removes the neuronal promoters but not the muscle-tracheal cell promoter. This deletion complements the flight defect of slowpoke null mutants but not the sticky-feet phenotype. Electrophysiological assays confirm that the ash2(18) chromosome restores normal electrical properties to the flight muscle. This suggests that the flight defect arises from a lack of slowpoke expression in muscle, whereas the sticky-feet phenotype arises from a lack of expression in nervous tissue.

Action Potentials↗
PubMed2000

Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4.

We present the cloning and characterization of two novel calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4, that are enriched in the testis and brain, respectively. We compare and contrast the steady state and kinetic properties of these beta subunits with the previously cloned mouse beta1 (mKCNMB1) and the human beta2 subunit (hKCNMB2). Once inactivation is removed, we find that hKCNMB2 has properties similar to mKCNMB1. hKCNMB2 slows Hslo1 channel gating and shifts the current-voltage relationship to more negative potentials. hKCNMB3 and hKCNMB4 have distinct effects on slo currents not observed with mKCNMB1 and hKCNMB2. Although we found that hKCNMB3 does interact with Hslo channels, its effects on Hslo1 channel properties were slight, increasing Hslo1 activation rates. In contrast, hKCNMB4 slows Hslo1 gating kinetics, and modulates the apparent calcium sensitivity of Hslo1. We found that the different effects of the beta subunits on some Hslo1 channel properties are calcium-dependent. mKCNMB1 and hKCNMB2 slow activation at 1 microM but not at 10 microM free calcium concentrations. hKCNMB4 decreases Hslo1 channel openings at low calcium concentrations but increases channel openings at high calcium concentrations. These results suggest that beta subunits in diverse tissue types fine-tune slo channel properties to the needs of a particular cell.

Amino Acid Sequence↗
PubMed2000

Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia.

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and liver/bone/kidney-type alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 12 families affected by severe or mild hypophosphatasia. Twenty distinct mutations were found, 5 of which were previously reported. Nine of the 15 new mutations were missense mutations (T117N, A159T, R229S, A331T, H364R, D389G, R433H, N461I, and C472S). The others were 2 nonsense mutations (L-12X and E274X), one single nucleotide deletion (1256delC), 2 mutations affecting splicing (298-2A>G, 997+2T>A), and a mutation in the major transcription start site (-195C>T). Hum Mutat 15:293, 2000.

Alkaline Phosphatase↗
PubMed2000

Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.

BACKGROUND: Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs). OBJECTIVE: This study compared hypericum and the SSRI sertraline in the treatment of depression. METHODS: In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks. RESULTS: The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size. CONCLUSION: The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.

Adolescent↗
PubMed2000

Efficacy and tolerability of olanzapine in elderly patients with psychotic disorders: a prospective study.

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

Aged↗
PubMed2000

Thyroid function screening in acute geropsychiatric admissions.

Thyroid function abnormalities have been associated with psychiatric illness. Even though it is a common practice to assess thyroid function in geropsychiatric patients, a literature search for the past 10 years did not reveal any published studies of assessments of thyroid function abnormalities in acute geropsychiatric populations. A retrospective chart review of 197 acute geropsychiatric inpatients and 14 comparison group patients showed that 40 geropsychiatric patients and 2 comparison group patients had abnormal thyroid function tests (TFfs). The most common abnormality was elevated triiodothyronine uptake (T3U), which was noted in 19 female and 13 male geropsychiatric patients. The difference in the prevalence of TFT abnormalities between the geropsychiatric patients and the comparison group subjects was not statistically significant. Both T3U and free thyroxine index (FTI) were significantly higher in the female geropsychiatric patients than in the female comparison group patients. The abnormalities in T3U and FTI in this study group may be related to an increased prevalence of unidentified systemic illness or to the presence of chronically poor nutrition.

Aged↗