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D Baker

Publications and source records attributed to D Baker.

At least 217 records · Page 12Linked to original sources
PubMed1995

A phage display system for studying the sequence determinants of protein folding.

We have developed a phage display system that provides a means to select variants of the IgG binding domain of peptostreptococcal protein L that fold from large combinatorial libraries. The premise underlying the selection scheme is that binding of protein L to IgG requires that the protein be properly folded. Using a combination of molecular biological and biophysical methods, we show that this assumption is valid. First, the phage selection procedure strongly selects against a point mutation in protein L that disrupts folding but is not in the IgG binding interface. Second, variants recovered from a library in which the first third of protein L was randomized are properly folded. The degree of sequence variation in the selected population is striking: the variants have as many as nine substitutions in the 14 residues that were mutagenized. The approach provides a selection for "foldedness" that is potentially applicable to any small binding protein.

Amino Acid Sequence↗
PubMed1995

Therapy of brown spider envenomation: a controlled trial of hyperbaric oxygen, dapsone, and cyproheptadine.

STUDY OBJECTIVE: To determine whether hyperbaric oxygen (HBO), dapsone, or cyproheptadine decreases the severity of skin lesions resulting from experimental Loxosceles envenomation. DESIGN: Randomized, blinded, controlled study. SETTING: Animal care facility. INTERVENTIONS: We used New Zealand white rabbits. All groups received 20 micrograms of pooled L deserta venom intradermally. Our control group received 4 ml of a 5% ethanol solution by oral gavage every 12 hours for 4 days. The HBO group received hyperbaric oxygen at 2.5 ATA for 65 minutes every 12 hours for 2 days, plus 5% ethanol solution for 4 days. The dapsone group received dapsone 1.1 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. The cyproheptadine group received cyproheptadine .125 mg/kg in 5% ethanol by gavage every 12 hours for 4 days. RESULTS: Total lesion size and ulcer size were followed for 10 days. The lesions were then excised, examined microscopically, and ranked by the severity of the histopathology. The groups did not differ significantly with respect to lesion size, ulcer size, or histopathologic ranking. CONCLUSION: Given the negative result in this study with adequate power to detect meaningful treatment benefits, we cannot recommend hyperbaric oxygen, dapsone, or cyproheptadine in the treatment of Loxosceles envenomation.

Animals↗
PubMed1995

The effect of a self-management training package on the transfer of aggression control procedures in the absence of supervision.

An aggression replacement and self-management training package reduced the frequency of aggressive behavior among four junior high adolescents identified as seriously emotionally disturbed (SED). During baseline sessions, the students were covertly filmed as they stood unsupervised in front of the school cafeteria. The four subjects engaged in aggressive behavior during 50% of the filmed intervals. These episodes involved provocation by other students, self-initiated provocation, or continuing interaction between students once an aggressive episode had begun. Treatment procedures included instruction, modeling, and role playing of aggression replacement skills. Self-management training included self-assessment, self-recording, and self-reinforcement. Following an 8-week period, subjects demonstrated substantial improvement in prosocial skills without supervision. During reversal-to-baseline conditions, aggressive behavior increased; however, reinstating treatment conditions brought a return to prosocial behavior. Outcomes suggest that aggressive replacement skills may transfer and sustain more adequately using self-management.

Adolescent↗
PubMed1995

Matching for MHC haplotypes results in improved survival following unrelated bone marrow transplantation.

Unrelated bone marrow donor-recipient pairs were assessed retrospectively for matching of the HLA-B, -C region (beta-block) and HLA-DR, DQ region (delta block) of the major histocompatibility complex (MHC) using a new DNA-based method referred to as MHC-block typing. The method utilises non-HLA DNA polymorphisms in the MHC as markers of blocks of ancestral haplotypes. Kaplan-Meier analysis of recipients who were matched at both the beta- and delta-blocks revealed a 6 months survival of 54%. Survival was better than for patients who were matched only by conventional criteria, including SSO-typing for class II.

Adult↗
PubMed1995

Correlation of bone marrow minimal residual disease and apparent isolated extramedullary relapse in childhood acute lymphoblastic leukaemia.

We have used a polymerase chain reaction (PCR) technique capable of detecting one leukaemic cell in 10(5) normal cells to monitor minimal residual disease (MRD) in a retrospective study of childhood ALL. We were particularly interested in comparing MRD findings in patients in long-term remission, bone marrow relapse and apparent isolated extramedullary relapse (EMR). Archival slides were initially studied from 21 patients. However, on subsequent analysis, only 15 patients were informative at the molecular level. All seven patients with EMR had evidence of MRD in the bone marrow at the time of relapse. Five of the seven also had evidence of bone marrow MRD prior to EMR. In one of the seven patients, MRD was not detected in a bone marrow sample studied 5 months prior to EMR. The remaining EMR patient was not studied prior to EMR. Of five patients who remained in long-term remission (mean 144 months), three did not have detectable MRD at the end of induction therapy (2 months) and all five were MRD-negative at the end of treatment (36 months). This contrasts with the three patients who relapsed in the bone marrow at 8, 15 and 88 months post-treatment and who had evidence of MRD at the end of therapy.

Bone Marrow↗
PubMed1994

Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice.

A recombinant protein corresponding to the Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) and synthetic 15-mer peptides of the whole MOG molecule with eight amino acid overlaps were screened for their ability to induce experimental allergic encephalomyelitis (EAE) in Biozzi AB/H (H-2dq1) and SJL (H-2S) mice. Clinical and histologic evidence of EAE developed after sensitization with the recombinant MOG protein in both AB/H and SJL mice. In AB/H mice at least three MOG epitopes within residues 1-22, 43-57, and 134-148 induced clinical and histologic EAE, whereas only the sequence 92-106 was encephalitogenic in SJL mice. Histologically, the inflammatory response in the central nervous system consisted of perivascular accumulations of CD5+ T cells and F4/80+ macrophage/microglia cells equally distributed in the brain and spinal cord. The subpial/meningeal infiltration, characteristic of mouse EAE induced with spinal cord homogenate, was only observed in cases of severe clinical disease in SJL mice in which the cellular infiltrates predominated in the spinal cord. In spite of the presence of histologic lesions in AB/H mice immunized with MOG, clinical disease either rapidly resolved or was clinically silent. In contrast to immunization of SJL mice with recombinant MOG, sensitization to MOG 92-106 induced severe clinical paralysis. After recovery these animals relapsed and exhibited demyelinated lesions. This study is the first to describe encephalitogenic epitopes of MOG that induce both clinical and histologic signs of EAE in mice. These and previous findings implicating MOG as a target Ag for Ab-mediated attack in EAE suggest that such autoreactivity to MOG may be significant in the development of human demyelinating diseases such as multiple sclerosis.

Amino Acid Sequence↗
PubMed1994

Influenza hemagglutinin: kinetic control of protein function.

In response to decreased pH, influenza hemagglutinin changes to a more stable conformation. Such changes, which can be controlled thermodynamically or kinetically, are the method by which many biological 'switches' are thrown.

Hemagglutinins, Viral↗
PubMed1994

Kinetics versus thermodynamics in protein folding.

Until quite recently it has been generally believed that the observed tertiary structure of a protein is controlled by thermodynamic and not kinetic processes. In this essay we review several recent results which call into question the universality of the thermodynamic hypothesis and discuss their implications for the understanding of protein folding.

Hemagglutinin Glycoproteins, Influenza Virus↗
PubMed1994

Clinical ehrlichiosis in a cat.

Clinical ehrlichiosis was diagnosed in a cat from Colorado on the basis of cytologic, serologic, and clinical findings. Clusters of gram-negative organisms that were morphologically similar to morulae of Ehrlichia spp were found only in mononuclear cells. The cat had clinical signs that were referable to infection by a rickettsial organism, and antibodies against E canis (titer, 1:80) and E risticii (titer, 1:40) were detected in serum. Exclusion of other obvious causes inducing similar clinical signs, and positive clinical response to doxycycline, an antibiotic with known antirickettsial actions, aided in diagnosis. The cat was clinically normal within days following initiation of treatment, and was clinically normal, as well as seronegative for antibodies against E canis and E risticii, 1,365 days after discharge.

Animals↗
PubMed1994

Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins.

Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-alpha was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10-100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.

Animals↗
PubMed1994

Experimental encephalomyelitis modulates inositol and taurine in the spinal cord of Biozzi mice.

In this high resolution magnetic resonance spectroscopic study of experimental allergic encephalomyelitis (EAE) and Semliki Forest virus (SFV) infection of the Biozzi AB/H mouse, marked increases in the initially low levels of N-trimethyl compounds in the spinal cord were observed during probable demyelinating episodes. There was also a pronounced and reproducible modulation of the levels of taurine and myo-inositol during acute and again during chronic relapsing EAE. The ratio of N-acetyl-aspartate to creatine in the spinal cord of mice infected with the mutant M9 strain of SFV decreased to approximately 70% of that seen in normal mice.

Alphavirus Infections↗
PubMed1994

Generality versus specificity: a comparison of dynamic and isometric measures of strength and speed-strength.

Considerable debate exists as to whether the qualities of muscle function exist as general or specific physiological capacities. If there is a generality of muscle function then strong relationships would exist between various measures of function for the same muscle(s), independent of the test contraction, mode or velocity. The purpose of this study was to examine the relationship between isometric and dynamic measures of muscle function to determine the existence of generality or specificity. A group of 22 men, experienced in weight training, were tested for lower and upper body dynamic and isometric measures of strength and speed-strength. The changes in these measures consequent to a resistance training programme were also investigated. The results of this study indicated that whilst isometric and dynamic measures of strength did significantly correlate (r = 0.57-0.61), the relationship was below that required to denote statistical generality. More important, the changes in isometric and dynamic strength consequent to a dynamic heavy resistance training programme were unrelated (r = 0.12-0.15). Thus the mechanisms that contribute to enhanced dynamic strength appeared unrelated to the mechanisms that contribute to enhanced isometric strength. Measures of dynamic and isometric speed-strength were unrelated, as were the changes in these measures resulting from training. The results of this study demonstrated that a generality of muscle function did not exist and that modality specific results were observed. Consequently this study calls into question the validity of isometric tests to monitor dynamically induced training adaptations.

Adult↗
PubMed1994

Intraosseous infusion: success of a standardized regional training program for prehospital advanced life support providers.

STUDY OBJECTIVE: To evaluate a standardized training program in intraosseous (IO) infusion for prehospital providers. DESIGN: Prospective multicenter 24-month study. SETTING: IO infusions were performed by prehospital providers from eight advanced life support units serving 14 hospitals within nine counties. PARTICIPANTS: Field advanced life support providers (paramedics and registered nurses). INTERVENTIONS: All providers participated in a one-hour standardized training session and supervised hands-on simulation. Providers completed a data sheet on all IO infusions performed. Data sheets were collected and summarized. RESULTS: One hundred thirty-four prehospital providers completed the training session and were approved to perform the procedure. Fifteen patients requiring IO infusion were encountered during the study period. Thirteen (87%) had IO infusion completed successfully. Clinical indications included 11 patients in cardiac arrest, two trauma resuscitations, one seizure, and one toxic ingestion. Patient ages ranged from 1 to 24 months. Seven patients were initially resuscitated. Four survived to hospital discharge. Procedural complications included one incidence of local fluid extravasation and one IO line that became dislodged en route. There were no complications at time of discharge in the four survivors. All procedures were performed in less than two minutes. CONCLUSION: A one-hour standardized training session was successfully used to train prehospital providers in the procedure of IO infusion. IO infusion then was implemented into their clinical practice with a satisfactory success rate and few complications.

Child, Preschool↗
PubMed1994

Development of the AHCPR-sponsored heart failure guideline: methodologic and procedural issues.

BACKGROUND: RAND, a nonprofit research and policy organization, served as contractor for the Agency for Health Care Policy and Research (AHCPR)-sponsored guideline on the management of patients with heart failure due to left-ventricular systolic dysfunction. PANEL: At meetings of the 16-member panel, discussions concerning practice recommendations were held until a consensus was reached. A draft algorithm was the key tool, serving as a starting point for panel discussion. The algorithm was revised after almost every panel meeting. KEY METHODS AND PROCEDURAL ISSUES: Early decisions included how best to (1) focus the guideline and literature review, (2) rate the strength of evidence underlying practice recommendations, and (3) determine the relationship between strength of evidence and strength of recommendation. In the absence of data, or when panelists did not share a common opinion, the panel attempted to achieve a consensus. An example of this process--when and how patients should be evaluated for possible coronary artery revascularization--is discussed at length. Unlike previous AHCPR guideline panels, this panel solicited opinions of national experts early and often during guideline development. This process helped the panelists arrive at conclusions on certain controversial issues. CONCLUSIONS: The guideline development process was complex and painstaking. The panelists and project staff believe that frequent peer review helped produce a guideline that can be widely accepted across clinical and geographic lines.

Algorithms↗
PubMed1994

Making judgements about treatment effectiveness based on health outcomes: theoretical and practical issues.

ISSUES: This article considers the problem of deciding which health care outcomes are important and relevant for (1) developing management recommendations for clinical practice guidelines and (2) evaluating patients' responses to treatment. DECISIONS: The Heart Failure Guideline Panel sponsored by the Agency for Health Care Policy and Research (AHCPR) decided that for both purposes the relevant outcomes are those experienced directly by patients: mortality and health-related quality of life (HRQOL). Changes in intermediate outcomes, such as test results of various kinds, were deemed insufficient evidence of effectiveness. CONCLUSIONS: In the context of heart failure, mortality risk (prognosis) can be measured using a variety of biochemical and physiological variables, but changes in these variables do not appear to correspond to changes in prognosis. For this reason, the Heart Failure Guideline Panel recommended that patients' responses to treatment be guided by signs and symptoms, rather than test results (for example, echocardiographic measurement of left-ventricular function or exercise-tolerance testing). HRQOL is best assessed by direct patient self-reports. Although patients may be influenced by a host of other variables (for example, mood, adaptation to chronic disease, placebo effect), self-reports will probably always represent the "gold standard" in assessing HRQOL. The reliability and validity of these reports can be enhanced by using standardized instruments or by incorporating questions from such instruments into the history-taking aspect of patient evaluation and monitoring. Finally, physical examination and submaximal exercise testing can provide additional information that can supplement patient reports. Information from these sources must be evaluated carefully in light of patients' self-reported HRQOL.

Health Status↗