Change in drug treatment after discharge from hospital.
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Drug Prescriptions↗
Biomedical subjects
J Burns
Publications and source records attributed to J Burns.
Bacterial toxin superantigens activate human T lymphocytes reactive with myelin autoantigens.
Some bacteria that are common human pathogens produce protein toxins that are potent activators of human T lymphocytes expressing certain types of T-cell receptors. In this study we examined the ability of staphylococcal toxins to stimulate human T lymphocytes that also recognized the myelin autoantigens myelin basic protein and proteolipid protein. T-cell populations responding to myelin basic protein or proteolipid protein were isolated from 4 subjects including 1 individual with multiple sclerosis. All myelin antigen-specific T cells responded in proliferation studies to at least one of the nine superantigenic toxins used in this study. The superantigenic toxins were up to 7 x 10(5)-fold more potent in proliferation assays than the myelin antigens to which the T cells were initially sensitized. In addition, cytotoxic, myelin basic protein-reactive T lymphocytes lysed antigen-presenting cells incubated with superantigenic toxins. These findings demonstrate a mechanism by which some bacterial infections might produce activation of myelin basic protein- and proteolipid protein-reactive T lymphocytes and perhaps contribute to demyelinating disease in humans.
Antigens, Bacterial↗
Biochemical and immunological evidence that the 11 kDa zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus.
The completed sequence of the arenavirus, lymphocytic choriomeningitis virus, revealed a new gene encoding a small protein with a single zinc-binding domain. The cDNA for this gene has been expressed in E. coli to produce fusion protein that has been used to raise antisera. The antisera facilitated the positive identification of the p11 'Z' gene product as a structural component of the virion. A related arenavirus, Tacaribe, has a comparable p11 gene product. The abundance of the p11 Z protein relative to other virion components has been determined by metabolic labeling. Triton X-114 extraction and dimethyl suberimidate-HCl crosslinking indicate that the p11 Z protein is a hydrophobic protein associated with the nucleocapsid of the virion core.
Amino Acid Sequence↗
Protective activity of a human respiratory syncytial virus immune globulin prepared from donors screened by microneutralization assay.
To explore the feasibility of preparing a human immune globulin specific for respiratory syncytial virus (RSV) by screening plasma donors, the ability of seven RSV antibody assays to identify plasma-yielding IgG with high virus-neutralizing and animal-protective activities was compared. IgG prepared from plasma units selected by microneutralization assay had significantly higher activity in protecting mice from respiratory RSV challenge than did IgGs prepared from plasmas selected by three direct ELISAs using purified F protein, G protein, or RSV-infected cell lysate, by two competitive ELISAs with RSV neutralizing monoclonal antibodies directed to the F2 or F3 epitopes of the F protein, or by plaque reduction neutralization. Relative to IgG made from unselected plasma, microneutralization-screened IgG was enriched fivefold by plaque-reduction neutralization assays done with or without complement. The microneutralization assay identified RSV antibodies with highest animal protective activity. This assay will be useful for identifying plasma donors for the preparation of a human immune globulin with high protective activity against RSV and deserves further evaluation for prediction of protective antibody concentrations in children.
Animals↗
Papillary hyperplasia of the lingual tonsil and sudden death in epilepsy.
Papillary hyperplasia of the lingual tonsils is a rare entity not previously reported at autopsy. We report a case that occurred in a 19-year-old man who died suddenly from his epilepsy, associated with aspiration of gastric contents. We describe the pathological features of this unusual condition, discuss the possible significance in this case and stress the importance of routine examination of the tongue and pharynx in every autopsy.
Adult↗
Caring for the patient with a pigtail drainage catheter.
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Chest Tubes↗
Necropsy study of association between sudden death and cardiac enzymes.
AIMS: To determine if cardiac enzymes measured at necropsy could be used to predict early myocardial infarction. METHODS: Cardiac enzyme activities were measured in body fluids at necropsy. Coroners' necropsies were grouped by gross and microscopic findings into cases of definite myocardial infarction, cases with occlusive coronary artery atheroma but no identifiable myocardial infarction, and non-cardiac cases. Pericardial fluid, peripheral venous blood, and blood from the right atrium were collected. Total creatine phosphokinase, creatine phosphokinase isoenzymes, aspartate aminotransferase and hydroxybutarate dehydrogenase activities were measured and the results analysed by logistic regression. RESULTS: The values of creatine phosphokinase and its isoenzymes were raised in those who had died of cardiac disease and were most discriminatory. Cases of early myocardial infarction without evidence of infarction on routine histological examination could be identified from enzyme activities. CONCLUSIONS: Measurement of cardiac enzymes in blood and pericardial fluid at necropsy can provide valuable additional information in cases of sudden death as a result of myocardial ischaemia which have occurred before macroscopic or microscopic evidence of myocardial infarction.
Arteriosclerosis↗
Immunoperoxidase localization of fibronectin in small bowel mucosa.
An indirect immunoperoxidase technique was employed to demonstrate fibronectin in cryostat sections of small bowel mucosa. Prior exposure of the sections to a solution of pepsin (4 mg/ml) was not essential to localize antigenicity of fibronectin immunohistologically.
Biopsy↗
Assessment of antigenic determinants for the human T cell response against myelin basic protein using overlapping synthetic peptides.
Immunization of experimental animals with myelin basic protein (MBP) or with specific MBP encephalitogenic determinants induces an autoimmune central nervous system (CNS) disease, experimental allergic encephalomyelitis, often studied as a model for human demyelinating disorders. This study examines the antigenic determinants of MBP recognized by human T cells using overlapping, synthetic peptides and T cell lines and clones isolated from four HLA-typed, neurologically normal subjects. T cell lines and clones isolated from individual subjects recognized at least one and as many as five distinct T cell determinants. In some instances the peptides recognized included determinants previously shown to induce experimental allergic encephalomyelitis (EAE) in experimental animals. In this group of four subjects, some determinants of MBP, including residues 5-25, 35-47, 65-75, and 81-100, were recognized by T cells derived from more than one individual suggesting that these regions may be particularly immunogenic for humans.
Antigen-Presenting Cells↗
Autoantigen-induced self lysis of human myelin basic protein-specific T lymphocytes.
Cytotoxic T cells reactive with myelin basic protein (MBP) may be isolated from most human subjects. Since activated T cells express major histocompatibility complex (MHC) class II antigens, we assessed whether MBP-specific, CD4+ T cells could present MBP or synthetic MBP peptides to themselves and whether this provoked self lysis. We examined two MBP-specific cell lines and eight T cell clones recognizing four different MBP epitopes. All T cell populations presented MBP as well as synthetic peptides to themselves eliciting self lysis of the T cell clones. CD4+ T cell populations recognizing another central nervous system (CNS) protein, proteolipid protein (PLP), or the recall antigen, Candida, did not exhibit this antigen-induced, autocytolytic activity. However, activated, PLP-reactive T cells were susceptible to lysis by cytotoxic MBP-specific T cells in the presence of MBP. These results suggest that antigen-induced self lysis of activated human T cells might limit an autoimmune response within a target organ independent of other immunoregulatory mechanisms.
Autoantigens↗
Failure of copolymer I to inhibit the human T-cell response to myelin basic protein.
In clinical trials, copolymer I (Cop 1) appears to reduce the number of exacerbations in early relapsing-remitting multiple sclerosis. The mechanism of this effect is uncertain, but Cop 1 also reduces the severity of experimental allergic encephalomyelitis and inhibits the response of murine myelin basic protein (MBP)-specific T cells. We tested MBP-specific T-cell lines and clones from four subjects to determine whether Cop 1 also limits the human response to MBP. We found no inhibition by Cop 1 of the human T-cell response to MBP.
Cell Division↗
Postgraduate medical fellowship training in alcoholism and drug abuse: national consensus standards.
This paper describes the historical background of the Consensus Standards for Postgraduate Medical Fellowships in Alcoholism and Drug Abuse, developed for the American Academy of Psychiatrists in Alcoholism and Addictions and the Association for Medical Education and Research in Substance Abuse. These standards were prepared by a National Advisory Committee of the Center for Medical Fellowships in Alcoholism and Drug Abuse, which includes 23 leading figures in academic medical training in the addiction field. The standards define general information, facilities and resources, the educational program, and the specific knowledge and skills appropriate to fellowship training. The standards were designed to provide a model for optimal training for residency affiliated fellowships to be used by faculty, trainees, and organizations setting training standards.
Alcoholism↗
Safety first: the key consideration. Management of clinical waste.
Strict protocols are required for the storage and disposal of waste. If staff are alerted to the correct procedures, and protective clothing and equipment is provided, potentially dangerous accidents can be prevented.
Humans↗
Identification of sequences of chromosome 7 that are expressed in sweat gland epithelial cells.
This paper describes an approach that can be used to identify specifically expressed coding sequences in defined regions of genomic DNA. We developed this method to identify expressed sequences from chromosome 7 located at or near the cystic fibrosis (CF) locus. Radioactively labelled single-stranded cDNAs derived from sweat gland epithelial cells and from fibroblasts were used to screen a genomic library constructed from flow-sorted chromosomes. Differential screening of phage lifts with these two probes yielded 36 different DNA segments. By using somatic cell hybrids containing different portions of chromosome 7, four of the clones were mapped to the 7q31 region in which the CF locus is located. These four clones and two others that gave strong differential epithelial signals but that were not within 7q31 were studied further. Restriction fragment length polymorphisms (RFLPs) were identified for two of the DNA segments within 7q31 and used for linkage analysis using a panel of CF families. One DNA segment was assigned to a location centromeric to the met locus. The other marker did not show recombination with CF but was subsequently excluded from the CF region by physical mapping. Three of the six DNA segments were found to hybridize to various RNAs using the Northern technique and therefore contain portions of genes. One of the clones showed strong differential expression when epithelial tissues were compared to fibroblasts and may represent an epithelium-specific gene.
Autoradiography↗
Discrimination of closely homologous HPV types by nonisotopic in situ hybridization: definition and derivation of tissue melting temperatures.
It is generally assumed that nucleic acid association during in situ hybridization reactions is similar to that of nucleic acid association in solution. This assumption has been investigated by detecting closely homologous human papillomavirus types 6 and 11 by in situ hybridization as a model for the evaluation of stringency conditions in clinical biopsies. By examining matched and mismatched, labelled and target sequences under various stringency conditions, empirical DNA-DNA stability curves and their derivative equations for tissue melting temperatures (Tmt) were derived. The corresponding values for Tmt are 10-20 degrees C higher than their solution equivalents. These data, supported by polymerase chain reaction experiments, demonstrate that closely homologous viral DNAs cross linked in tissue by formaldehyde fixation do not interact with the corresponding labelled probes as predicted from solution kinetic equations. This not only has theoretical implications but is also relevant to the accuracy of clinical diagnostic testing.
Base Sequence↗
Fluorescent dextrans as sensitive anterograde neuroanatomical tracers: applications and pitfalls.
We have examined five conjugated 10,000 mol. wt. dextrans as potential anterograde tract tracers: Lucifer Yellow, Texas Red, fluorescein, Cascade Blue and tetramethylrhodamine. Pressure injections were made into the brain, dorsal root ganglia or footpads of adult rats. The retrograde tracer Fluoro-Gold was injected alone or mixed with the dextrans before injection. Three-14 days after injection, animals were perfused and sections cut with a freezing microtome. Texas Red-, fluorescein- and tetramethylrhodamine-conjugated dextrans produced intense labeling of neuronal cell bodies, axons and dendritic processes at the injection site and were transported by neurons predominantly in an anterograde direction to yield terminal and preterminal labeling. Relative to the fluorescein and tetramethylrhodamine conjugates, the quality and intensity of the anterograde labeling produced by Texas Red was variable. Results with Lucifer Yellow and Cascade Blue conjugates were negative. Optimal results were produced by slow-pressure injections via glass micropipettes. In comparison with Fluoro-Gold, retrograde transport by the dextran conjugates was present, but limited in its extent. Injections of the tetramethylrhodamine conjugate into dorsal root ganglia produced anterograde labeling of afferent fibers in visceral organs and injections into the nucleus ambiguous labeled motor fibers in the esophagus. Double/triple labeling was observed in the brain and spinal cord following multiple injections of fluorescein, tetramethylrhodamine and Fluoro-Gold. Also, Fluoro-Gold could be mixed with one of the dextrans in order to produce specific retrograde and anterograde labeling from the same injection site. The conjugates were compatible with fluorescent immunocytochemical procedures, but proved unsuitable for peripheral injections.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Development of an automated procedure for fluorescent DNA sequencing.
We describe here the development of a procedure for complete automation of the dideoxynucleotide DNA sequencing chemistry using fluorescent dye-labeled oligonucleotide primers. This procedure combines rapid preparation of template DNA using a modification of the polymerase chain reaction, automation of the DNA sequencing reactions using a robotic laboratory workstation, and subsequent analysis of the fluorescent-labeled reaction products on a commercial automated fluorescent sequencer. Using this procedure, we were able to produce sufficient quantities of template DNA directly from bacterial colonies or bacteriophage plaques, perform the DNA sequencing reactions on these templates, and load the reaction products on the fluorescent DNA sequencer in a single work day. This scheme for automation of the fluorescent DNA sequencing method allows the fluorescent sequencer to be run at its full capacity every day and eliminates much of the labor required to obtain a high level of data output. Currently, we are able to perform and analyze 16 fluorescent-labeled reactions every day, with an average output of over 7000 bp per sequencer run.
Automation↗
Venepuncture for calcium assays: should we still avoid the tourniquet?
Blood was collected by venepuncture from nine healthy subjects over a ten minute period before applying a standard tourniquet, and over a ten minute period afterwards. Plasma ionised calcium was unaltered by the tourniquet, whereas total calcium, total protein and albumin in serum increased modestly. However, there was no effect on total calcium adjusted for albumin. Even without albumin adjustment the change in total calcium was negligible within one minute of the application of the tourniquet. We consider that in ordinary clinical practice, there is no need to perform venepuncture for calcium assays without a tourniquet.
Blood Proteins↗