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Biomedical subjects

D Graves

Publications and source records attributed to D Graves.

35 records · Page 2Linked to original sources
PubMed1992

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.

Animals↗
PubMed1992

Intravascular membrane oxygenation and carbon dioxide removal--a new application for permissive hypercapnia?

Pressure limited ventilation or "lung rest" may prevent further exacerbation of acute lung injury from high airway pressures. A therapeutic goal of an intracorporeal oxygenation and carbon dioxide removal device (IVOX) is reduction of airway pressures. We noted increased IVOX CO2 removal as mixed venous CO2 increased in experimental animals. However, we recognize the limited clinical utility of removing approximately 30% of venous CO2. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) was used in 5 patients with respiratory failure, and again we noted improved CO2 removal with increasing mixed venous CO2 concentrations. Preliminary calculations demonstrate that a CO2 gradient of approximately 70 mm Hg is needed to remove 100 ml CO2/min. The use of more aggressive permissive hypercapnia protocols with IVOX may permit further reduction in airway pressure without problems of severe respiratory acidosis.

Adolescent↗
PubMed1992

Outbreak of ceftazidime resistance due to a novel extended-spectrum beta-lactamase in isolates from cancer patients.

Ceftazidime is widely used in the therapy of infectious complications in neutropenic patients. We studied an outbreak of ceftazidime-resistant gram-negative bacillary infections in pediatric cancer patients receiving empirical ceftazidime therapy for neutropenic fever. Fourteen isolates (12 Klebsiella pneumoniae and 2 Escherichia coli) from 13 patients were studied. Specimens were obtained from multiple clinical sites including blood, urine, throat, and lung. The organisms were resistant to ceftazidime, aztreonam, and penicillins but remained susceptible to cephamycins and imipenem. All resistant isolates produced a novel beta-lactamase (TEM-26) with a pI of approximately 5.58, which was transferred by transformation to E. coli on a 7.9-kb nonconjugative plasmid which cotransferred resistance to trimethoprim-sulfamethoxazole. This enzyme readily hydrolyzed ceftazidime, aztreonam, and penicillins in a spectrophotometric assay. DNA sequencing data suggest that TEM-26 is derived from TEM-1.

Bacteria↗
PubMed1992

Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1.

Interleukin-6 (IL-6) is a peptide whose properties include the ability to activate T-lymphocytes, stimulate the secretion of immunoglobulin, induce neuronal differentiation, and trigger the release of acute phase proteins. We have detected IL-6-like activity in conditioned medium from cultured human retinal pigment epithelial (RPE) cells with a bioassay based on the ability of IL-6 to induce the proliferation of murine B-9 plasmacytoma cells. Biologic activity increased approximately 90-fold when the cells were cultured in the presence of IL-1 alpha (30 units/ml). Western blot analysis confirmed that conditioned medium from IL-1 alpha-stimulated RPE cells contained peptides with molecular weights ranging between 19,000 and 30,000 and reactive with antibody to IL-6. Finally, Northern blot analysis indicated that cells cultured in the presence of interleukin-1 contained a 1.2 kilobase transcript that hybridized to a cDNA probe specific for IL-6 messenger RNA. IL-6 peptide on Western blots and mRNA on Northern blots were undetectable unless cells were cultured in the presence of IL-1 alpha. Although IL-6 is synthesized by a variety of cell types, this report is the first to detect its synthesis by an eye-specific cell type. Furthermore, these observations indicate that retinal pigment epithelial cells respond to IL-1, a cytokine that previously has been implicated in ocular inflammation.

Blotting, Northern↗
PubMed1989

Structural analysis of the gene for human acidic fibroblast growth factor.

Genomic clones derived from the gene for human acidic fibroblast growth factor (aFGF) have been isolated. Nucleotide sequence analysis of these clones revealed that the coding region of the human aFGF gene is interrupted by two introns, located at precisely homologous locations to introns in four other members of the FGF gene family, strongly indicating a common evolutionary origin for these genes. Northern blot analyses of the multiple aFGF transcripts found in serum-stimulated human foreskin fibroblasts indicated that the aFGF gene also contains a third intron, lying in the 5' untranslated region.

Amino Acid Sequence↗
PubMed1986

Antithyroid antibodies in Hispanic patients with type I diabetes mellitus. Prevalence and significance.

Antithyroglobulin antibodies (ATA) and antithyroid microsomal antibodies (AMA) were sought and thyroid function was determined in 90 Hispanic patients with type I diabetes mellitus followed up for up to seven years. We detected ATA in 7.5% of our patients and AMA in 34.8%. All serum samples positive for ATA also contained AMA. There was no sex difference in the prevalence of thyroid autoimmunity. A small, firm goiter was present in eight patients, one of whom developed Graves' disease. Our results suggest that a relatively high prevalence of AMA and no sex difference in thyroid autoimmunity may be unique features of Hispanic children and adolescents with type I diabetes mellitus. Such patients should be clinically evaluated for thyroid dysfunction and should be screened annually for the presence of AMA. When antibodies are present, laboratory evaluation of thyroid function should be performed frequently.

Adolescent↗
PubMed1973

Comparison of the direct agglutination and indirect hemagglutination tests in the determination of blood serum titers to Escherichia coli organisms.

A comparison of the direct agglutination test and the indirect hemagglutination test for the detection of blood serum antibodies to Escherichia coli organisms indicated that these serological tests were comparable. In some instances the indirect hemagglutination test provided higher endpoint readings. Preparation of the antigens for the indirect hemagglutination test was more time consuming than for the direct agglutination test. Crude extract and purified polysaccharides were comparable as red blood cell sensitizing agents.

Agglutination Tests↗
PubMedDate not supplied

Substrate and inhibitor recognition of protein kinases: what is known about the catalytic subunit of phosphorylase kinase?

Although much can be learned about the specificity of protein kinases from studies with peptide substrates, the question remains, how do kinases recognize their three-dimensional protein substrates? Information derived from such studies provides further understanding of substrate recognition and can facilitate the design of specific protein kinase inhibitors. Phosphorylase kinase (PhK) catalyzes the phosphorylation of phosphorylase b (phos. b) to form the active phosphorylase a. No other protein kinase can duplicate this reaction. Why? To probe this question and establish what features in the protein are important for substrate binding and product release, mutants of phos. b have been studied. This report shows how mutations change the properties of the protein substrate and the ability of these mutants to be phosphorylated by PhK and other kinases. Action of protein kinases on their substrates is often regulated by autoinhibitory segments. The C-terminus of the catalytic gamma-subunit of PhK contains two inhibitory sites overlapping two calmodulin-binding regions. These two peptide segments resemble sequences in phos. b and may explain why peptides of these regions are potent inhibitors of PhK. We will show results with peptide inhibitors, using various expressed forms of the catalytic subunit, which describe their modes of interaction and mechanisms of inhibition. Metal ions can change molecular interactions. With PhK, Mn2+ facilitates the use of GTP as a phosphoryl group donor and greatly increases phosphorylation of a tyrosine residue in angiotensin II. This implies that the spatial arrangement of specificity determinants can be manipulated so that PhK can utilize other substrates.

Animals↗
PubMedDate not supplied

Longitudinal assessment of play and adaptive behavior in young children with developmental disabilities.

Deficits in appropriate play have been widely documented among children with developmental disabilities. However, there has been little research on the development of play or the relation between play and adaptive behavior in such children. The present study involved a longitudinal assessment of play and adaptive behavior among 13 preschool children with developmental disabilities. Children were assessed every 6 months over a 3-year period. Assessments included standardized ratings of adaptive behavior and videotape observations during unstructured free-play times in the preschool classroom. Adaptive behavior increased by almost one standard deviation from the first to the last round of data collection. Appropriate play was observed during approximately 20% of each 30-min observation and showed little overall change over 3 years of study. Observed play was primarily functional (57%) and exploratory (28%) with less constructive (5%) and pretend (10%) play. Adaptive behavior scores were not consistently correlated with the amount or type of play. The results suggest little overall relation between appropriate play and other major domains of adaptive behavior. Implications for play-based assessment and intervention in early childhood special education are discussed.

Autistic Disorder↗
PubMedDate not supplied

Amplification and expression of heterologous oncostatin M in Chinese hamster ovary cells.

A stable Chinese hamster ovary (CHO) cell line producing high levels of human oncostatin M (OM) was generated by transfecting a heterologous gene coding for the protein. This novel construct was comprised of the gene for the transforming growth factor-beta 1 (TGF-beta 1) signal peptide fused to the gene for mature human OM. Amplification with methotrexate produced milligram quantities of this recombinant OM, which was processed correctly, glycosylated, and found to have biological functions similar to those of natural OM.

Animals↗
PubMedDate not supplied

Referring patients for domiciliary care.

This article attempts to identify some of the reasons why patients who meet the referral criteria of domiciliary palliative nursing care services are not referred. A study was conducted among district nurses and GPs which highlighted that a 'conspiracy of silence' still existed between patients, professionals and families. A desire to manage patients themselves and a misunderstanding of the work of Macmillan nurses were also reported. Some recommendations for change are made.

Community Health Nursing↗
PubMedDate not supplied

Hemispheric contributions to pragmatics.

Twenty-seven patients with right-hemisphere damage (RBD) and thirty-one patients with left-hemisphere damage (LBD) received a new pragmatics battery in Hebrew consisting of two parts: (1) comprehension and production of basic speech acts (BSAs), including tests of assertions, questions, requests, and commands, and (2) comprehension of implicatures, including implicatures of quantity, quality, relevance, and manner. Each test had a verbal and a nonverbal version. Patients also received Hebrew versions of the Western Aphasia Battery and of the Right Hemisphere Communication Battery. Both LBD and RBD patients were impaired relative to controls but did not differ from each other in their overall scores on BSAs and on Implicatures when scores were corrected by aphasia and neglect indices. There was a systematic localization of BSAs in the left hemisphere (LH) but not in the right hemisphere (RH). There was poor localization of Implicatures in either hemisphere. In LBD patients, BSAs were associated with language functions measured with the WAB, suggesting the radical possibility that the classic localization of language functions in aphasia is influenced by the localization of the BSAs required by aphasia language tests. Both BSAs and implicatures show greater functional independence from other pragmatic, language and cognitive functions in the RBD than in the LBD patients. Thus, the LH is more likely to contain an unmodular domain-nonspecific set of central cognitive mechanisms for applying means-ends rationality principles to intentional activity.

Brain↗
PubMedDate not supplied

Detection of human Pneumocystis carinii by the polymerase chain reaction.

Oligonucleotide primers were prepared from a clone (B12) which has been shown to be a repetitive sequence in the rat P. carinii genome. Polymerase chain reaction was employed to amplify both rat and human P. carinii DNA. The detection limit of the assay was approximately 600 ng of total nucleic acid. Amplification products from both the rat and human isolates (ca. 780 bp) were characterized by denaturing gradient gel electrophoresis after digestion with Sau3A. No amplification products were obtained when DNA from the following potential pulmonary pathogens were used in identical reactions: Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans, Mycobacterium avium-intracellulare and cytomegalovirus. In a blind study using the B12 primers, P. carinii DNA was successfully amplified in clinical samples which were positive by direct immunofluorescence assay (IFA) as well as in some specimens not identified by direct IFA.

Animals↗