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Biomedical subjects

G Walter

Publications and source records attributed to G Walter.

At least 37 records · Page 2Linked to original sources
PubMed2001

The pharmacologic treatment of the early phase of first-episode psychosis in youths.

OBJECTIVES: To summarize available knowledge about pharmacologic treatments that are used for first-onset (or early) psychosis in youths, with particular consideration of the prodromal stage and the effectiveness and safety of novel antipsychotic drugs and mood stabilizers. METHOD: A computerized search of medical databases (for example, Medline and Embase), a manual searching of articles and textbooks, and the use of vignettes to highlight treatment issues. RESULTS: There are limited data about the effectiveness and safety of psychotropic agents for youths with psychosis and scarce information about the drug treatment of the prodromal stage of early psychosis in all age groups. The available data are encouraging, although the newer agents are not without safety concerns. CONCLUSIONS: Despite the paucity of studies, there is a range of psychotropics that may be used in the early stages of psychotic illness in youths. Drug choice is influenced by several factors, including the clinical picture, side effect profile, and patient preference. In certain situations, the decision may be not to use medication.

Adolescent↗
PubMed2001

Resistance of different surfactant preparations to inactivation by meconium.

A disease similar to acute respiratory distress syndrome may occur in neonates after aspiration of meconium. The aim of the study was to compare the inhibitory effects of human meconium on the following surfactant preparations suspended at a concentration of 2.5 mg/mL: Curosurf, Alveofact, Survanta, Exosurf, Pumactant, rabbit natural surfactant from bronchoalveolar lavage, and two synthetic surfactants based on recombinant surfactant protein-C (Venticute) or a leucine/lysine polypeptide. Minimum surface tension, determined with a pulsating bubble surfactometer, was increased >10 mN/m at meconium concentrations >or=0.04 mg/mL for Curosurf, Alveofact, or Survanta, >or=0.32 mg/mL for recombinant surfactant protein-C, >or=1.25 mg/mL for leucine/lysine polypeptide, and >or=20 mg/mL for rabbit natural surfactant. The protein-free synthetic surfactants Exosurf and Pumactant did not reach minimum surface tension <10 mN/m even in the absence of meconium. We conclude that surfactant activity is inhibited by meconium in a dose-dependent manner. Recombinant surfactant protein-C and leucine/lysine polypeptide surfactant were more resistant to inhibition than the modified natural surfactants Curosurf, Alveofact, or Survanta but less resistant than natural lavage surfactant containing surfactant protein-A. We speculate that recombinant hydrophobic surfactant proteins or synthetic analogs of these proteins can be used for the design of new surfactant preparations that are relatively resistant to inactivation and therefore suitable for treatment of acute respiratory distress syndrome.

Animals↗
PubMed2001

Protein array technology. Potential use in medical diagnostics.

The human genome is sequenced, but only a minority of genes have been assigned a function. Whole-genome expression profiling is an important tool for functional genomic studies. Automated technology allows high-throughput gene activity monitoring by analysis of complex expression patterns, resulting in fingerprints of diseased versus normal or developmentally distinct tissues. Differential gene expression can be most efficiently monitored by DNA hybridization on arrays of oligonucleotides or cDNA clones. Starting from high-density filter membranes, cDNA microarrays have recently been devised in chip format. We have shown that the same cDNA libraries can be used for high-throughput protein expression and antibody screening on high-density filters and microarrays. These libraries connect recombinant proteins to clones identified by DNA hybridization or sequencing, hence creating a direct link between gene catalogs and functional catalogs. Microarrays can now be used to go from an individual clone to a specific gene and its protein product. Clone libraries become amenable to database integration including all steps from DNA sequencing to functional assays of gene products.

Diagnosis↗
PubMed2001

High-throughput screening of surface displayed gene products.

With the human genome project approaching completion, there is a growing interest in functional analysis of gene products. The characterization of large numbers of proteins, their expression patterns and in vivo localisations, demands the use of automated technology that maintains a logistic link to the encoding genes. As a complementary approach, phage display is used for recombinant protein expression and the selection of interacting (binding) molecules. Cloning of libraries in filamentous bacteriophage or phage mid vectors provides a physical link between the expressed protein and its encoding DNA sequence. High-throughput technology for automated library handling and phage display selection has been developed using picking-spotting robots and a module for pin-based magnetic particle handling. This system enables simultaneous interaction screening of libraries and the selection of binders to different target molecules at high throughput. Target molecules are either displayed on high-density filter membranes (protein filters) or tag-bound to magnetic particles and can be handled as native ligands. Binding activity is confirmed by magnetic particle ELISA in the microtitre format. The whole procedure from immobilisation of target molecules to confirmed clones of binders is automatable. Using this technology, we have selected human scFv antibody fragments against expression products of human cDNA libraries.

Bacteriophages↗
PubMed2000

By-passing selection: direct screening for antibody-antigen interactions using protein arrays.

We have developed a system to identify highly specific antibody-antigen interactions by protein array screening. This removes the need for selection using animal immunisation or in vitro techniques such as phage or ribosome display. We screened an array of 27 648 human foetal brain proteins with 12 well-expressed antibody fragments that had not previously been exposed to any antigen. Four highly specific antibody-antigen pairs were identified, including three antibodies that bind proteins of unknown function. The target proteins were expressed at a very low copy number on the array, emphasising the unbiased nature of the screen. The specificity and sensitivity of binding demonstrates that this 'naive' screening approach could be applied to the high throughput isolation of specific antibodies against many different targets in the human proteome.

Antibodies↗
PubMed2000

Noninvasive measurement of gene expression in skeletal muscle.

We have developed a noninvasive detection method for expression of viral-mediated gene transfer. A recombinant adenovirus was constructed by using the gene for arginine kinase (AK), which is the invertebrate correlate to the vertebrate ATP-buffering enzyme, creatine kinase. Gene expression was noninvasively monitored using (31)P-magnetic resonance spectroscopy ((31)P-MRS). The product of the AK enzyme, phosphoarginine (PArg), served as an MRS-visible reporter of AK expression. The recombinant adenovirus coding for arginine kinase (rAdCMVAK) was injected into the right hindlimbs of neonatal mice. Two weeks after injection of rAdCMVAK, a unique (31)P-MRS resonance was observed. It was observable in all rAdCMVAK injected hindlimbs and was not present in the contralateral control or the vehicle injected limb. PArg and phosphocreatine (PCr) concentrations were calculated to be 11.6 +/- 0.90 and 13.6 +/- 1.1 mM respectively in rAdCMVAK injected limbs. AK activity was demonstrated in vivo by monitoring the decreases in PArg and ATP resonances during prolonged ischemia. After 1 h of ischemia intracellular pH was 6.73 +/- 0.06, PCr/ATP was decreased by 77 +/- 8%, whereas PArg/ATP was decreased by 50 +/- 15% of basal levels. PArg and PCr returned to basal levels within 5 min of the restoration of blood flow. AK activity persisted for at least 8 mo after injection, indicating that adenoviral-mediated gene transfer can produce stable expression for long periods of time. Therefore, the cDNA encoding AK provides a useful reporter gene that allows noninvasive and repeated monitoring of gene expression after viral mediated gene transfer to muscle.

Adenoviridae↗
PubMed2000

A human cDNA library for high-throughput protein expression screening.

We have constructed a human fetal brain cDNA library in an Escherichia coli expression vector for high-throughput screening of recombinant human proteins. Using robot technology, the library was arrayed in microtiter plates and gridded onto high-density filter membranes. Putative expression clones were detected on the filters using an antibody against the N-terminal sequence RGS-His(6) of fusion proteins. Positive clones were rearrayed into a new sublibrary, and 96 randomly chosen clones were analyzed. Expression products were analyzed by SDS-PAGE, affinity purification, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, and the determined protein masses were compared to masses predicted from DNA sequencing data. It was found that 66% of these clones contained inserts in a correct reading frame. Sixty-four percent of the correct reading frame clones comprised the complete coding sequence of a human protein. High-throughput microtiter plate methods were developed for protein expression, extraction, purification, and mass spectrometric analyses. An enzyme assay for glyceraldehyde-3-phosphate dehydrogenase activity in native extracts was adapted to the microtiter plate format. Our data indicate that high-throughput screening of an arrayed protein expression library is an economical way of generating large numbers of clones producing recombinant human proteins for structural and functional analyses.

Algorithms↗
PubMed2000

Antiestrogenic activities of 3,8-dihydroxy-6,11-dihydrobenzo[a]carbazoles with sulfur-containing side chains.

The objective of this study was to explore whether the conversion of the 2-phenylindole system into the tetracyclic benzo[a]carbazole changes the endocrine profile when the side chain structure was kept constant. Five different sulfur-containing side chains were linked to the nitrogen of the tetracycle. The biological evaluation revealed that the character of the indole derivatives remained unchanged after the conversion to the respective benzocarbzoles but the potency decreased by one order of magnitude. In vitro, all derivatives acted as pure antiestrogens without any agonist activity. They strongly inhibited the growth of estrogen-sensitive MCF-7 breast cancer cells with IC50-values in the nanomolar range. In the mouse uterine weight test, the derivatives with an aliphatic side chain were devoid of estrogenic activity and antagonized the effect of estradiol. The presence of an aromatic ring in the side chain gave rise to significant agonist activity in vivo independently of the carrier structure. All data revealed the equivalence of both carrier structures in respect to the endocrine profile but showed a decrease in potency upon the conversion of the 2-phenylindole system into the benzocarbazole structure.

Animals↗
PubMed2000

Studies on human porin XXI: gadolinium opens Up cell membrane standing porin channels making way for the osmolytes chloride or taurine-A putative approach to activate the alternate chloride channel in cystic fibrosis.

We recently proposed that cell-membrane-integrated vertebrate porin/voltage-dependent anion-selective channel (VDAC) forms part of the outwardly rectifying chloride channel (ORCC) complex that may be involved in volume regulation. The results we present here support this thesis. According to light scattering measurements micromolar concentrations of Gd(3+) induce cell swelling of human healthy and cystic fibrosis (CF) B-lymphocyte cell lines in isotonic Ringer solution. In high-potassium Ringer solution additional swelling is observed. Gd(3+) induces excessive cell swelling of cell lines in hypotonic Ringer solutions, containing 70 mM NaCl or 135 mM taurine, respectively. The gadolinium effect is lost when NaCl is replaced by Na-gluconate. Using video camera monitoring we show that HeLa cells also swell in micromolar concentrations of Gd(3+) in isotonic taurine Ringer solution. The dose-dependent effect of the agonist was always blocked by extracellular application of anti-human type-1 porin antibodies. Together with data on a decreasing effect of micromolar amounts of gadolinium on the voltage dependence of reconstituted human porin the results prove the involvement of porin channels in the swelling behavior in different cell lines. As a mechanism we propose that ionic gadolinium opens up plasmalemma-integrated porin channels, chloride or taurine then following their concentration gradients into the cells. Furthermore, our data argue for a single pathway for inorganic and organic osmolytes during regulatory volume decrease after cell swelling. There is indirect evidence that porin forms part of the cystic fibrosis relevant ORCC channel. Gadolinium thus may work to open the alternate chloride channel in CF.

Antibodies, Monoclonal↗
PubMed2000

Studies on human porin XXII: cell membrane integrated human porin channels are involved in regulatory volume decrease (RVD) of HeLa cells.

Cell volume regulation receives increasing attention not only as the basis of regulatory volume increase or regulatory volume decrease (RVD) of cells in surroundings of changing osmolarity, but also appears to be relevant in cell proliferation, differentiation, and apoptosis. A central event in RVD is the opening of a volume-sensitive chloride/anion channel(s), and blocking this pathway would abolish RVD. This is shown here with monoclonal mouse anti-human type-1 porin antibodies, proving that porin is involved in this process. HeLa cells preincubated with these antibodies dramatically increase their volume within about 1 min after a hypotonic stimulus by 70 mM NaCl Ringer solution, but do not move back toward their starting volume, thus indicating abolished RVD. Corresponding effects are induced by the established anion channel inhibitor DIDS. Video camera monitoring of cell size over time was used as a direct and noninvasive approach. We had already accumulated evidence that plasmalemma integrated eukaryotic porin channels form chloride/anion channels in this cell compartment and that they are involved in cell volume regulation. Finally, the present data again demonstrate the suitability of our anti-porin antibodies in physiological studies.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2000

[Ventrodorsal correction and instrumentation in idiopathic scoliosis].

A number of different procedures are used for the surgical treatment of King II scoliosis. One reason for the controversial discussion in this context is that the term King II scoliosis is usually inadequate, because there are partly marked clinical and radiological differences in this type of curvature. From January 1996 to December 1997, a total of 26 patients with rigid King II scoliosis were submitted to a ventrodorsal procedure. Twenty-three patients were included in the study. The indication for this procedure was established in cases with a secondary lumbar curvature of at least 50 degrees as well as unsatisfactory straightening of the primary and secondary curvature in the bendings and inadequate horizontal positioning of the caudal end vertebra of not less than 10 degrees. Ventral Derotation-Spondylodesis (VDS) and Dorsal correction-Spondylodesis (DKS) led to a thoracic and lumbar straightening from 68.4 degrees to 13.2 degrees and from 61.4 degrees to 17.8 degrees, respectively. The tilt of the vertebra instrumented farthest caudally was corrected from 21.2 degrees to 4.9 degrees. The thoracic hypokyphosis was improved from 16.6 degrees to 25.1 degrees. In 11 patients, the dorsal instrumentation was extended to the caudal end vertebra, in another 11 patients, instrumentation was achieved up to a vertebra cranial from the end vertebra. The correction loss and complication rate was extremely low. Based on the surgical goals discussed further down, combined application of VDS and DKS is efficient and suitable in conjunction with the indication described. The complication rate is quite low. The different types of King II scoliosis have to be differentiated preoperatively.

Adolescent↗
PubMed2000

Relationship between muscle T2* relaxation properties and metabolic state: a combined localized 31P-spectroscopy and 1H-imaging study.

A multi-volume 31P-magnetic resonance spectroscopy localization procedure was implemented to compare directly muscle metabolism and proton T2* relaxation properties in the human plantar flexor muscles during exercise. Localized 31P-spectra were collected simultaneously from the medial gastrocnemius, lateral gastrocnemius and soleus muscles during exercise using beta1-insensitive Hadamard Spectroscopic Imaging (HSI). 1H T2*-weighted gradient-echo images were acquired at rest and immediately following high-intensity plantar flexion exercise. T2* mapping of the individual calf muscles showed that plantar flexion with the knee extended produces significant increases (P < 0.0001) in the mean (SEM) T2* of the medial [35.6 (1.2) ms vs 28.5 (0.5) ms at rest] and lateral gastrocnemius [35.6 (0.9) ms vs 26.2 (0.9) ms at rest], but not in the soleus [26.7 (0.6) ms vs 27.3 (0.8) ms at rest]. In accordance with the changes in T2*, the ratio of inorganic phosphate to phosphocreatine (Pi:PCr) and the intracellular muscle pH shifted significantly in the gastrocnemii, while the soleus showed no change in muscle pH and only a moderate increase in Pi-to-Ph. Comparison of spectroscopic and relaxation parameters in both gastrocnemius muscles revealed a significant relationship between post-exercise T2* and intracellular pH (r = 0.72-0.76) and Pi-to-Ph ratios (r = 0.81-0.88) during exercise. Using an improved method of localization, this study confirms the existence of a strong relationship between transverse relaxation properties and the metabolic state in skeletal muscles engaged in heavy exercise.

Exercise↗
PubMed2000

Protein arrays for gene expression and molecular interaction screening.

The array format has revolutionised biomedical experimentation and diagnostics, enabling ordered high-throughput analysis. During the past decade, classic solid phase substrates, such as microtitre plates, membrane filters and microscopic slides, were turned into high-density, chip-like structures. The concept of the arrayed library was central to this development which now extends from DNA to protein. The new and versatile protein array technology allows high-throughput screening for gene expression and molecular interactions. As a major platform for functional genomics, it is already on its way into medical diagnostics.

Bacterial Proteins↗
PubMed2000

Patterns of use, attitudes and expectations of mental health staff regarding computers.

There is limited information on the views of mental health staff about computers. The present study aimed to ascertain the patterns of use, attitudes and expectations of staff from a comprehensive mental health service regarding computers before and after the purchase of new equipment and training. A questionnaire was sent to staff of the Central Sydney Mental Health Services working in sites targeted for new computer equipment and training. Most respondents, especially those with computer experience or who had worked in mental health for less than 5 years, viewed computers favourably. At the same time, half the respondents did not feel they had sufficient access to a computer at work and the vast majority had not received training as intended. Commitments to provide computer equipment and training must be followed through, otherwise staff may feel disenchanted and computers may be regarded less favourably. A measure of the positive views about computer use ('positivity index') developed during the course of the current study may have wider applicability.

Adult↗
PubMed2000

Psychiatrists' experience and views regarding St John's Wort and 'alternative' treatments.

OBJECTIVE: This study aims to ascertain the experience and views of psychiatrists in relation to St John's Wort and alternative treatments generally. METHOD: A questionnaire was posted to all members of the Royal Australian and New Zealand College of Psychiatrists living in Australia or New Zealand. RESULTS: Of the 1910 mailed questionnaires, 862 (45%) were returned. Eighty per cent of respondents had patients who had used the herb. Side-effects and drug interactions were reported by 28% and 8% respectively of these psychiatrists. Some adverse events were described as serious. Psychiatrist attitudes about St John's Wort and alternative treatments were positive overall and psychiatrists seemed willing to recommend St John's Wort despite limited evidence of its usefulness. CONCLUSIONS: Psychiatrists in Australia and New Zealand regularly manage patients who take St John's Wort and a considerable number actually recommend the treatment. However, they also report side-effects and drug interactions. Psychiatrists should routinely enquire about their patients' use of alternative treatments, be mindful of possible side-effects and in particular be aware of the dangers of combining St John's Wort with other psychotropics.

Adult↗
PubMed2000

Way out of tune: lessons from Shine and its exposé.

OBJECTIVE: The depiction of David Helfgott's life presented in the movie Shine is at odds with other public accounts, notably one by his sister, Margaret. These significant discrepancies have sparked a prolonged media debate and provide the opportunity to examine cinema's apparent ground rules governing depictions of psychiatry in film, the media values and pressures which are claimed to limit the scope of these portrayals, and the implications for psychiatry. METHOD: Information was obtained from a number of sources, including Shine, books about the movie and Shine film paraphernalia, other films about mental illness, the psychiatric papers on cinema, media images of mental illness and media values, and through discussions with fellow mental health professionals, consumers, carers and media specialists. RESULTS: David Helfgott emerges as an undoubtedly remarkable and resilient individual, who, together with his family, was vulnerable to, and may have experienced, exploitation and violation through the cinema. CONCLUSIONS: Filmmakers should reconcile media values and constraints with considerations of ethics and public accountability. Marrying these considerations is both possible and compatible with good filmmaking and audience appeal. There is the potential for a story about those who have mental illness to be told from multiple points of view without compromising dramatic power.

Australia↗
PubMed2000

Family environment in attention deficit hyperactivity, oppositional defiant and conduct disorders.

OBJECTIVE: This study aims to ascertain whether there were differences in family environment among patients with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder and conduct disorder. METHOD: The records of 233 patients, selected for high or low scores on a scale that taps ADHD symptoms, were reviewed by three clinicians who made DSM-IV diagnoses and rated the family environment with the Global Family Environment Scale (GFES). Self-report data obtained from the parent and child versions of the Child Behaviour Checklist were also used. The quality of the family environment was then compared between the various diagnostic groups. RESULTS: A poorer family environment was associated with conduct disorder and oppositional defiant disorder and predicted a worse outcome (e.g. admission to a non-psychiatric institution, drug and alcohol abuse). Quality of the family environment did not vary according to ADHD diagnosis or gender. CONCLUSIONS: There seems to be no association between the quality of the family environment and a diagnosis of ADHD among referred adolescents. However, there is an association with conduct disorder. Interventions that improve family environment in the early years of life may prevent the development of conduct problems.

Adolescent↗