Search PubMed⌕ Search

Biomedical subjects

G Walter

Publications and source records attributed to G Walter.

At least 19 recordsLinked to original sources
PubMed2002

Functional significance of gap junctional coupling in preimplantation development.

Gap junctional intercellular coupling allows cells to share low molecular weight metabolites and second messengers, thus facilitating homeostatic and developmental processes. Gap junctions make their appearance very early in rodent development, during compaction in the eight-cell stage. Surprisingly, preimplantation mouse embryos lacking the gap junction protein connexin 43 develop normally and establish full-term pregnancies despite severely reduced gap junctional coupling. It was suggested that this might be explained by the presence of at least five additional connexins known to be expressed in blastocysts. In the present study, we set out to clarify the number of connexins present in preimplantation rodent embryos and the role of gap junctional coupling, if any, in blastocyst development. We provide evidence from reverse transcription-polymerase chain reaction analysis that the genes encoding 3 additional connexins (connexin 30 or beta6, connexin 36 or alpha9, and connexin 57 or alpha10) are also transcribed in preimplantation mouse embryos. Furthermore, we show that multiple connexins are expressed in rat preimplantation embryos, indicating that multiplicity of connexin expression may be a common feature of early mammalian embryogenesis. We could detect no up-regulation of any of 3 coexpressed connexins examined in mouse embryos lacking connexin 43. Impaired intercellular coupling caused either by the loss of connexin 43 or by treatment of cultured embryos with the gap junctional coupling blocker 18alpha-glycyrrhetinic acid (AGA) had no discernable effect on either apoptosis or glucose utilization, parameters known to be affected by gap junctional coupling in other contexts. These results, taken together with the reported inability of AGA to perturb blastocyst formation, imply that gap junctional coupling is not essential during this developmental period. We propose that connexin expression and the assembly of multiple types of gap junction channels in preimplantation embryos facilitates the diversification of communication pathways that will appear during postimplantation development. New evidence of this diversification is presented using rat blastocyst outgrowths.

Animals↗
PubMed2002

Nanocrystalline alpha-Ni(OH)2 prepared by ultrasonic precipitation.

Nanocrystalline alpha-Ni(OH)2 was prepared by an ultrasonic precipitation/stirring method. Results of X-ray diffraction, transmission electron microscopy, infrared, and thermogravimetric measurements confirm that the sample obtained is alpha phase. Compared with the sample prepared without ultrasonic stirring, the crystal structure of the alpha phase sample has been changed from beta phase. The crystalline size of the sample is about 20 nm, which is smaller than the sample produced without ultrasonic stirring (70 nm).

Chemical Precipitation↗
PubMed2001

Gadolinium as an opener of the outwardly rectifying Cl(-) channel (ORCC). Is there relevance for cystic fibrosis therapy?

There is indirect evidence that the plasmalemma-integrated eukaryotic porin (the voltage-dependent anion-selective channel, VDAC) functions as the outwardly rectifying chloride channel (ORCC). The channel, which is believed to play a role in cell volume regulation, appears to be relevant for cystic fibrosis (CF) therapy, in that it may function as an alternative Cl(-) channel. In the present study we showed first that Gd(3+) altered the voltage dependence of human type-1 porin incorporated into artificial planar lipid bilayers. Next, using a light-scattering approach on transformed normal or CF human B-lymphocytes in hypotonic Ringer solution, we found slightly differing regulatory volume decrease (RVD) curves for the cell lines under study. Addition of 15-60 microM GdCl3 in hypotonic Ringer increased light scattering, pointing to cell swelling beyond normal values. RVD was not observed in those experiments. A corresponding effect was seen in isotonic Ringer containing GdCl3. In either osmotic situation Gd(3+)-induced cell swelling was abolished by monoclonal mouse anti-human type-1 porin antibodies. Agonist and antibody effects were dose dependent. Finally, videocamera-monitored control experiments with adherent HeLa cells verified the direct effect of the agonist on cell swelling in hypo- or isotonic situations and its prevention by the antibodies. We conclude that GdCl3 opens plasmalemma-integrated porin channels, allowing ions to following their gradients, resulting in cell swelling. Since respiratory epithelium expresses porin channels in the apical membrane, the use of gadolinium to activate ORCC may represent a new therapeutic approach in CF.

Anti-Inflammatory Agents↗
PubMed2001

Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene.

Protein phosphatase 2A (PP2A) consists of three subunits, A, B and C. The A and B subunits have regulatory functions while C is the catalytic subunit. PP2A core enzyme is composed of subunits A and C, and the holoenzyme of subunits A, B and C. All subunits exist as multiple isoforms or splice variants. The A subunit exists as two isoforms, A alpha and A beta. Here we report about the properties of eight A beta mutants, which were found in human lung and colon cancer. These mutants were reconstructed by site-directed mutagenesis and assayed for their ability to bind B and C subunits. Two mutants showed decreased binding of PR72, a member of the B" family of B subunits, but normal C subunit binding; two mutants exhibited decreased binding of the C subunit and of B"/PR72; and one mutant showed increased binding of both the C subunit and B"/PR72. Of three mutants that behaved like the wild-type A beta subunit, one is a polymorphic variant and another one is altered outside the binding region for B and C subunits. Importantly, we also found that the wild-type A alpha and A beta isoforms, although 85% identical, are remarkably different in their ability to bind B and C subunits. Our findings may have important implications in regard to the role of PP2A as a tumor suppressor.

Amino Acid Sequence↗
PubMed2001

Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the A alpha subunit gene.

The A subunit of protein phosphatase 2A (PP2A) consists of 15 nonidentical repeats. The catalytic C subunit binds to C-terminal repeats 11 - 15 and regulatory B subunits bind to N-terminal repeats 1 - 10. Recently, four cancer-associated mutants of the A-alpha subunit have been described: Glu64-->Asp in lung carcinoma, Glu64-->Gly in breast carcinoma, Arg418-->Trp in melanoma, and Delta171 - 589 in breast carcinoma. Based on our model of PP2A, we predicted that Glu64-->Asp and Glu64-->Gly might be defective in B subunit binding, whereas Arg418-->Trp and Delta171 - 589 might bind neither B nor C subunits. We generated these mutants by site-directed mutagenesis and assayed their ability to associate with different forms of B subunits (B, B', B") or with the catalytic C subunit. The results demonstrate that all mutants are defective in binding either B or B and C subunits. Specifically, the N-terminal mutants, Glu64-->Asp and Glu64-->Gly, are defective in B' but normal in B, B", and C subunit binding, whereas the C-terminal mutants Arg418-->Trp and Delta171 - 589 bind none of the B subunits nor the C subunit. The implications of these findings with regard to the potential role of PP2A as a tumor suppressor are discussed. Oncogene (2001) 20, 10 - 15.

Amino Acid Sequence↗
PubMed2001

Reduced expression of the Aalpha subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the Aalpha and Abeta subunit genes.

Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit, C, and the regulatory subunits, A and B. The A and C subunits both exist as 2 isoforms (alpha and beta) and the B subunit as multiple forms subdivided into 3 families, B, B' and B". It has been reported that the genes encoding the Aalpha and Abeta subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether Aalpha and Abeta mutations occur in human gliomas. Using single strand conformational polymorphism analysis and DNA sequencing, 58 brain tumors were investigated, including 23 glioblastomas, 19 oligodendrogliomas and 16 anaplastic oligodendrogliomas. Only silent mutations were detected in the Aalpha gene and no mutations in the Abeta gene. However, in 43% of the tumors, the level of Aalpha was reduced at least 10-fold. By comparison, the levels of the Balpha and Calpha subunits were mostly normal. Our data indicate that these tumors contain very low levels of core and holoenzyme and high amounts of unregulated catalytic C subunit.

Alleles↗
PubMed2001

Publishing ethics in psychiatry.

OBJECTIVE: The ethics of publishing in psychiatry has gained only limited attention. We examine, in a historical context, pertinent ethical problems and offer a series of recommendations for dealing with them. METHOD: The study was conducted by exploration of medical databases and websites, and systematic discussion with ethicists, legal experts, publishers and researchers. RESULTS: Serious 'publishing misconduct' appears to have been rare in the psychiatric literature, but any occurrence of redundant publication, plagiarism and publication of fraudulent or inhumane research is disturbing and should be prevented. Difficulties around authorship, sensitive use of language, conflict of interest and bias in the publishing process are additional issues claiming our attention. CONCLUSIONS: A clearly articulated publishing ethos is desirable. Potential strategies to achieve this include devising guidelines on publishing ethics, teaching the subject to new writers, journals committing themselves to the ethical dimension of their operations, and penalising colleagues who violate agreed principles of good conduct.

Ethics, Professional↗
PubMed2001

Transcranial magnetic stimulation: experience, knowledge and attitudes of recipients.

OBJECTIVE: To examine the experience, knowledge and attitudes of recipients of transcranial magnetic stimulation (TMS) regarding the treatment. There have been no studies of patient views about TMS. METHOD: A 60-item survey was administered by telephone to persons with depressive illness who received TMS at Royal Hobart Hospital, Tasmania. RESULTS: Forty-eight patients were interviewed. About two-thirds also had a history of treatment with electroconvulsive therapy (ECT). Experience and opinions about TMS were generally very positive. Almost three-quarters of interviewees believed TMS had been helpful. The vast majority rated TMS as more acceptable than having, or the prospect of having, ECT. The majority would have TMS again and would recommend it to others. CONCLUSIONS: The mostly favourable experiences and attitudes reported by interviewees will be reassuring to patients, their families and treating health professionals when TMS is being considered.

Adult↗
PubMed2001

The humble case report.

OBJECTIVE: There is negligible systematic information about case reports in the psychiatric literature. We aimed to describe case report articles published in the Australian and New Zealand Journal of Psychiatry (ANZJP), to provide data about the quality of evidence they offer, to ascertain changes over time and to make recommendations, based on our findings, about these articles. METHOD: All articles describing cases which appeared in the ANZJP between 1967 and 1999 were identified and examined. RESULTS: 256 articles describing a total of 479 cases were published over the study period. Fifty-five per cent of articles reported an unusual presentation. Thirty-eight per cent of cases had a mood disorder and 24% had a psychosis. Seventy-six per cent of patients had a positive outcome. Cases published in 1989-1999 were more likely to describe pharmacological treatments than cases published earlier. CONCLUSIONS: Clinical descriptions that lead to progress are undervalued. Case reports should retain a place in the ANZJP, provided they convey information that is new and useful (e.g. suggesting or refuting hypotheses) rather than simply document current practice or describe the unusual. Issues of patient consent and anonymity also warrant consideration.

Evidence-Based Medicine↗
PubMed2001

Characteristics of adolescents with school refusal.

OBJECTIVE: To describe the characteristics of young people presenting with school refusal to a child and adolescent psychiatric unit and examine differences between those admitted for inpatient treatment and the rest. METHOD: One hundred and ninety-two adolescents who had been assessed or treated for school refusal between 1994 and 1998 at the Rivendell Unit, Sydney, Australia were identified. An instrument was developed and used to gather data from files. Diagnoses were made by the consensus of two of the investigators using DSM IV criteria from all sources of information. RESULTS: The commencement of school refusal generally occurred in the first 2 years of high school. School refusers had a high prevalence not only of anxiety, but also of mood and disruptive behaviour disorders. A family history of psychiatric illness was present in over half the sample. There were no differences between those subsequently admitted as inpatients and the rest in terms of symptom scores, family composition, family conflict, family separation or history of abuse. Those admitted for inpatient treatment were more likely to have a diagnosis of mood disorders and comorbid diagnoses and to have a maternal history of psychiatric illness. CONCLUSIONS: School refusal in adolescence can be a symptom of a variety of disorders, particularly anxiety and mood disorder. Treatment programs need to be geared to the range of diagnoses which occur in this patient group and to the various circumstances associated with the onset of the problem.

Adolescent↗
PubMed2001

The Impact Factor: time for change.

OBJECTIVE: The Impact Factor (IF) has received virtually no attention in the psychiat ric literature, despite its long-term use, expanding influence and evidence of misapplication. We examine the IF's validity as a measure of a paper's scientific worth, and consider alternative ways to conduct such an appraisal. METHOD: We explored medical databases and websites, and conferred with acknowledged experts on the subject. RESULTS: Irremediable problems, both conceptual and technical, make the IF a flawed measure. The notion that citations vouch for the quality of an article is questionable. Moreover, the IF's vulnerability to misuse in domains such as academic promotion and research grant assessment is a serious development. CONCLUSION: The IF (and all measures derived from it) should be abandoned. A "return to basics" in evaluating published work is overdue. As seductive as a simple formula is to assess quality, shortcuts are unavailable and unlikely to be useful. Publishing a short-list of papers annually, judged as objectively as possible by peers to merit special attention, may be a more meaningful option. Conceivably, every psychiatric journal could participate in this cyclical exercise, leading to a "grand short-list". This could be made readily available to all professionals, both researchers and clinicians, by being posted on a suitable website. Since peer review has a long-standing role in scientific publishing, our proposal is essentially an extension of that process.

Abstracting and Indexing↗
PubMed2001

Transcranial magnetic stimulation in young persons: a review of known cases.

There are no published data about transcranial magnetic stimulation (TMS) as a treatment for psychiatric disorders in young persons. The aim of this article is to collate available information about TMS in this population. Information was sought, by placing a message on the TMS Listserver, from investigators who had used TMS in patients 18 years of age or younger. Only one group reported experience in this area; it had treated seven patients, ages 16-18 years. Three patients had unipolar depression, three had schizophrenia, and one had bipolar disorder. Five of the seven patients had improved by the conclusion of the TMS course. Adverse events were reported in one patient. Further studies are needed first to investigate systematically the safety of TMS in children and adolescents and second to examine its potential therapeutic effects in this population.

Adolescent↗
PubMed2001

Electroconvulsive therapy for minors: experiences and attitudes of child psychiatrists and psychologists.

OBJECTIVE: To estimate knowledge, experience, and attitudes towards the use of electroconvulsive treatment in minors (patients < 18 years of age), among child and adolescent psychiatrists and psychologists. METHOD: 1,600 questionnaires were mailed to a group of child and adolescent psychiatrists and psychologists. RESULT: There were 625 (39%) respondents. 329 (53.8%) of the respondents stated that they possessed minimal knowledge about the use of ECT in children and adolescents. Lack of confidence in providing a second opinion was common and reported by 75%. Compared with those with minimal knowledge, respondents with advanced knowledge reported a higher perception of safety and efficacy. The majority (70%) of the respondents regarded ECT as a treatment of last resort. CONCLUSION: Many child and adolescent psychiatrists and psychologists have very little knowledge, training, or experience in this treatment. They seem to be ill equipped to appropriately consider or advise patients and families about ECT. Clinical and research implications of these findings are discussed.

Adolescent↗
PubMed2001

The portrayal of ECT in American movies.

OBJECTIVE: To describe the portrayal of electroconvulsive therapy (ECT) in American films. This has not been systematically studied previously, despite some notorious ECT scenes in the history of American cinema and the impact of films on audiences. METHOD: All movies depicting or making reference to ECT were identified from a number of sources. Available movies were viewed on at least two occasions. RESULTS: 22 films, beginning with The Snake Pit and ending with Requiem for a Dream, portraying or making reference to ECT were made between 1948 and 2000. 20 (91%) of these movies were obtained and viewed. CONCLUSION: Having commenced its movie career as a severe but helpful remedy for personal distress, ECT on film has become a progressively more negative and cruel treatment, leaving the impression of a brutal, harmful, and abusive maneuver with no therapeutic benefit.

Electroconvulsive Therapy↗
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↗