Biomedical subjects
B Weiss
Publications and source records attributed to B Weiss.
Overproduction and physical characterization of SoxR, a [2Fe-2S] protein that governs an oxidative response regulon in Escherichia coli.
SoxR protein governs the soxRS (superoxide response) regulon of Escherichia coli by becoming a transcriptional activator when the cells are exposed to compounds that mediate univalent redox reactions, many of which produce superoxide as a by-product. SoxR was overproduced and purified to near homogeneity from a strain bearing an expression vector. It could bind specifically to the soxS operator even in the absence of RNA polymerase. The aerobically purified protein, which is readily autooxidized, could activate the transcription of soxS DNA even without exposure to known inducing agents. SoxR is a globular homodimer. It contains one [2Fe-2S] cluster per polypeptide chain, as demonstrated by optical and EPR spectroscopy combined with stoichiometric analysis of iron content, unpaired-electron-spin density, and reduction by dithionite. The protein is active in its oxidized ([2Fe-2S]2+) state. The presence of a prosthetic group capable of univalent redox reactions may help to explain the activation of the regulon in vivo by compounds that can mediate such reactions.
Continuous infusion of clozapine increases mu and delta opioid receptors and proenkephalin mRNA in mouse brain.
The biochemical mechanisms involved in the actions of the atypical antipsychotic clozapine are still unclear. Because elevated levels of enkephalin in certain areas of the central nervous system may be necessary for antipsychotic activity, we have examined the effect of clozapine on certain receptors and mRNA transcripts involved in the opioid peptidergic system. Clozapine was infused continuously into mice for 21 days and the density of mu and delta opioid receptors was measured in the brains by quantitative receptor autoradiography, and the level of proenkephalin mRNA and dopamine D1 and D2 receptor mRNA were measured by in situ hybridization histochemistry. The results showed that continuous infusion of clozapine increased the density of D1 but not D2 receptors. However, it failed to alter the levels of either D1 or D2 dopamine receptor mRNA. By contrast, clozapine increased the density of mu and delta opioid receptors and increased the levels of proenkephalin mRNA. These results indicate that continuous treatment with clozapine increases opioid peptidergic activity in mouse brain and suggest that alteration of peptidergic activity as well as alteration of dopaminergic activity may be involved in its antipsychotic action.
Managed care 1995. Managed care: there's no stopping it now.
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Magnetization transfer in hemopoietic bone marrow examined by localized proton spectroscopy.
The sensitivity of hemopoietic bone marrow to magnetization transfer is analyzed in 15 healthy volunteers and seven patients with different hematological disorders (inflammation, plasmacytoma, hemopoietic reconstitution after bone marrow transplantation). To obtain sufficient signal-to-noise ratio, a 90 degrees - 180 degrees - 180 degrees double spin echo (PRESS) single voxel spectroscopic method was combined with pulsed magnetization transfer. Several spectra were recorded from each volume element inside the vertebral marrow, alternately with and without prepulses for magnetization transfer. Water signals from marrow with increased content of extracellular water due to inflammation or edema revealed less magnetization transfer effects than marrow with increased intracellular water content due to high cellularity. The preliminary results show magnetization transfer to be a promising tool for the clinically important characterization of the water composition in red bone marrow.
Magnetic resonance imaging reveals a markedly inhomogeneous distribution of marrow cellularity in a patient with myelodysplasia.
A 47-year-old male patient with myelodysplasia showed increasing values of serum lactate dehydrogenase (up to 3500 units/l) and an increasing blast count. Several biopsies (taken from the posterior iliac crest) revealed marked hypocellularity. In contrast, magnetic resonance imaging of the marrow demonstrated an inhomogeneous distribution of marrow with hypocellular and also large hypercellular areas not detected by cytological and histological analysis. A location for biopsy of hypercellular marrow was provided by T1-weighted and water-selective magnetic resonance imaging. The findings in the patient were compared with those in a matched healthy volunteer.
Characterization of bone marrow after transplantation by means of magnetic resonance.
Magnetic resonance (MR) has become a new tool for noninvasive characterization of bone marrow in patients with hematological disorders in the past few years. Experiences gained from 1H MR imaging and spectroscopic investigations in 48 healthy volunteers and more than 130 patients with hematological disorders are reported and interpreted. Twenty-four of the patients underwent bone marrow transplantation (BMT) before the MR examinations. The findings in these studies provided noninvasive characterization and monitoring of vertebral marrow after BMT. Specifically, MR techniques were found to be suitable for studies of different aspects in physiological and pathological alterations of bone marrow: The water content within the marrow can be analyzed by chemical-shift selective-imaging techniques with good spatial resolution. Spectroscopic methods also allow more sensitive quantification of the signal fractions, as well as separate evaluation of the relaxation times of water and lipids. Relaxometry might be useful to characterize the cellular and extracellular portions of water molecules. Furthermore, the distribution of the magnetic field within small-volume elements of vertebral marrow can be measured. The field distribution is influenced by the trabecular density and the composition of the marrow. High amounts of hemosiderin in the marrow result in clearly broadened field distributions, demonstrated by increasing line widths in MR proton spectra. Magnetic resonance techniques can be used to assess not only the cellularity of the bone marrow, but also metabolic alterations in this compartment which result from cytotoxic treatment or immunological processes.
Localization of fruit tree viruses by immuno-tissue printing in infected shoots of Malus sp. and Prunus sp.
Immuno-tissue printing protocols for the localization of apple chlorotic leaf spot virus (ACLSV), stem grooving virus (SGV) and plum pox virus (PPV) in shoots of Prunus and Malus in vitro have been established for routine diagnosis in a virus elimination program. Since these viruses belong to different virus genera, the protocols were adapted according to the properties of the virus under investigation. Accumulation of ACLSV was highest in the base of the stem and decreased towards the apex of the shoots. ACLSV was found in the epidermis, the cortex, in the vascular bundles, but seldom in the pith tissue of in vitro apple shoots. ACLSV immuno-tissue printing was as sensitive as ELISA and the intensity of color signals in immuno-tissue prints correlated with absorbance values by two-step ELISA. SGV could be detected by immuno-tissue prints at infectivity levels, where it reacted negative in ELISA. SGV accumulated in the vascular bundles, occurred locally in the parenchymatic tissue, was found in high amounts in young leaves near the meristem, but not within the meristem. PPV was detected in all tissue types of stem sections with an irregular pattern reflecting the in vivo situation causing problems with detection. Discrimination of poorly and heavily infected shoots was possible with the naked eye.
Immunocytochemical localization of calmodulin in PC12 cells and its possible interaction with histones.
The subcellular localization of calmodulin, a multi-functional calcium-binding regulatory protein, was examined immunocytochemically in undifferentiated PC12 rat pheochromocytoma cells and cells differentiated with nerve growth factor (NGF) and dibutyryl cyclic AMP. In undifferentiated PC12 cells, diffuse immunostaining for calmodulin was observed in the cytoplasm, and weak, patch-like staining was found in the nucleus. In differentiated cells, intense immunostaining for calmodulin was observed in the cytoplasm, while nuclear immunostaining was still evident. Immunoreactivity for calmodulin was also observed along newly-formed neuritic processes, with strong staining in varicosity-like structures and growth cones. Using double-label immunochemistry, the relative intensity of immunostaining for calmodulin among the nuclei was found to correlate with the relative intensity of immunostaining for histones in the same nuclei. A comparison of a profile of 125I-calmodulin binding in the nuclear fraction from PC12 cells to that of immunoblotting for histones in the same fraction indicated that some of the histones are calmodulin-binding proteins in PC12 cells. These results show that the level and subcellular distribution of calmodulin are altered during the course of nerve cell differentiation and suggest the possibility that histones may function as major nuclear binding proteins for calmodulin.
Relative effectiveness of behavioral versus nonbehavioral child psychotherapy.
Some researchers have concluded that, for children and adolescents, behavioral interventions may be more effective than nonbehavioral interventions. Other researchers, however, have proposed artifactual hypotheses for the apparent superiority of behavioral treatments. In this study, one such hypothesis was evaluated: that the apparent superiority of behavioral interventions among children is due to differences in the methodological quality of studies of behavioral and nonbehavioral treatments. Meta-analytic results reported in this article found little support for this hypothesis.
Bridging the gap between laboratory and clinic in child and adolescent psychotherapy.
Meta-analyses of laboratory outcome studies reveal beneficial effects of psychotherapy with children and adolescents. However, the research therapy in most of those lab studies differs from everyday clinic therapy in several ways, and the 9 studies of clinic therapy the authors have found show markedly poorer outcomes than research therapy studies. These findings suggest a need to bridge the long-standing gap between outcome researchers and clinicians. Three kinds of bridging research are proposed and illustrated: (a) enriching the research data base on treatment effects by practitioners in clinical settings--including private practice and health maintenance organizations, (b) identifying features of research therapy that account for positive outcomes and applying those features to clinical practice, and (c) exporting lab-tested treatments to clinics and assessing their effects with referred youths. If these bridging strategies were widely adopted, despite the numerous obstacles described herein, real progress might be made toward more effective treatment in clinical practice.
Effects of psychotherapy with children and adolescents revisited: a meta-analysis of treatment outcome studies.
A meta-analysis of child and adolescent psychotherapy outcome research tested previous findings using a new sample of 150 outcome studies and weighted least squares methods. The overall mean effect of therapy was positive and highly significant. Effects were more positive for behavioral than for nonbehavioral treatments, and samples of adolescent girls showed better outcomes than other Age x Gender groups. Paraprofessionals produced larger overall treatment effects than professional therapists or students, but professionals produced larger effects than paraprofessionals in treating overcontrolled problems (e.g., anxiety and depression). Results supported the specificity of treatment effects: Outcomes were stronger for the particular problems targeted in treatment than for problems not targeted. The findings shed new light on previous results and raise significant issues for future study.
Effectiveness of psychotherapy.
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Antigen-independent reactivation of anti-E, years after allogeneic bone marrow transplantation: a case report.
Nine years after allogenic bone marrow transplantation a strong anti-E was observed in a patient transplanted with bone marrow from his HLA-identical brother. This IgG anti-E, with a titre of 4000, was detected together with autoantibodies to red blood cells and platelets and was not induced by transfusion with E+ cells. The hypothesis is proposed that the anti-E represents either antigen-independent desuppression of the donor immune system sensitized at the time of bone marrow transplantation by E antigens in the recipient, or antigen-independent memory B-cell activation by Epstein-Barr virus infection.
A multimethod study of problem behavior among Thai and American children in school: teacher reports versus direct observations.
Previous literature describes Thai children as unusually polite, deferent, and behaviorally restrained. Yet, in a recent study employing teacher reports, Thai children were reported to show many more behavior problems than American children. Such a finding may reflect culture-linked differences in the perspective of Thai versus American teachers. To explore this possibility, we used trained observers to conduct direct observations of Thai and American children's school behavior, and we obtained teacher reports on the same children. Observational results were precisely the opposite of previous and present teacher-report findings: Observers reported twice as much problem behavior and off-task behavior in American children as in their Thai age-mates. This pattern may reflect Thai-U.S. differences in teachers' style, societal values and practices, even child temperament. The finding support the value of direct behavior observation in cross-national research on child problems.
D2 dopamine receptor antisense oligodeoxynucleotide inhibits the synthesis of a functional pool of D2 dopamine receptors.
In vivo administration of an antisense oligonucleotide targeted toward the D2 dopamine (DA) receptor mRNA (D2 AS) markedly inhibited D2 receptor-mediated behaviors but produced only a relatively small reduction in the levels of D2 DA receptors in mouse striatum. This apparent dissociation between DA receptor-mediated behaviors and the levels of D2 DA receptors was addressed by inhibiting the total number of D2 DA receptors by intraperitoneal administration of the selective, irreversibly acting D2 DA receptor antagonist fluphenazine-N-mustard (FNM) and then determining the effects of D2 AS, administered intracerebroventricularly, on the rate of synthesis of D2 DA receptors and on the recovery of D2 receptor-mediated behaviors. FNM inactivated approximately 90% of D2 DA receptors within 4 hr of treatment, after which the receptors returned to normal levels by approximately 8 days. D2 AS treatment significantly inhibited the rate of recovery of D2 DA receptors in striatum of FNM-treated mice. FNM treatment also produced a number of behavioral alterations, including catalepsy, and the inhibition of stereotypic behavior induced by the D2/D3 DA receptor agonist quinpirole. Both of these behaviors returned to normal within 8 days after FNM treatment. D2 AS treatment delayed the restoration of these FNM-induced behaviors. Thus, it reduced the rate of disappearance of the cataleptic behavior induced by FNM and significantly delayed the restoration of the stereotypic behavior induced by quinpirole. The changes induced by D2 AS on D2 receptor-mediated behaviors were reversed on cessation of D2 AS treatment. A random oligomer given in the same amount and for the same length of time as that of the D2 AS had no significant effects on either D2 DA receptor synthesis or DA receptor-mediated behaviors. These studies demonstrate that in vivo administration of D2 AS decreased the rate of recovery of D2 DA receptors and inhibited the recovery of D2 DA receptor-mediated behaviors after irreversible receptor inactivation and suggest that D2 AS treatment inhibits the synthesis of a functional pool of D2 DA receptors.
Re: Dose as central variable in toxicology.
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Perspectives on methylmercury as a global health hazard.
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