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Biomedical subjects

J S Johnson

Publications and source records attributed to J S Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Managing aggression in a psychiatric hospital using a behaviour plan: a case study.

This paper focuses on the critical role of nursing in implementing a behaviour plan in a psychiatric hospital. The plan was implemented with a 40-year-old man with a long history of aggression towards others and self. The study used a single-subject research design with baseline and intervention phases (AB Design). Data were collected on (1) frequency of incidents of aggression towards others and self; (2) use of restrictive interventions to manage aggression (i.e. restraints, pro re nata medication, 1:1 special observation); and (3) frequency of staff injury. The data show a decrease in frequency of aggression towards others and self, a concurrent reduction in the use of restrictive interventions to manage aggression, and a decrease in incidents of staff injury. The behaviour plan helped staff maintain a safe and therapeutic milieu. The behaviour plan has given the patient an opportunity to learn positive replacement behaviours and skills, and the opportunity eventually to leave the hospital to live in a less restrictive community home.

Adult↗
PubMed2006

Truncated gamma-glutamyl carboxylase in rambouillet sheep.

A flock of Rambouillet sheep was examined because of increased lamb mortality due to ineffective hemostasis at parturition. Decreased activities of coagulation factors II, VII, IX, and X, and severely reduced hepatic gamma-glutamyl carboxylase activity with adequate vitamin K 2,3 epoxide reductase activity was determined.(1,)(21) Parenteral vitamin K(1) supplementation did not improve vitamin K-dependent coagulation factor activities in 3 affected lambs. Affected lamb gamma-glutamyl carboxylase deoxyribonucleic acid was sequenced, and 4 single nucleotide polymorphisms (SNPs 2-5) of the gamma-glutamyl carboxylase gene were identified. Single nucleotide polymorphism-4 results in an arginine to stop codon (UGA) substitution, which prematurely terminates the peptide at residue 686 (R686Stop). This genotype (GATT/GATT) has a strong association with the coagulopathy observed in clinically affected lambs, P < 0.001. The frequency of SNP-3 in exon 11 (R486H) within the MARC 1.1 database is high in the US sheep population overall. Gamma-glutamyl carboxylase activity in hepatic microsomes from a SNP-3 homozygous lamb lacking the SNP-4 mutation (GACC/GACC) was similar to control sheep homozygous for arginine at 486 and also lacking SNP-4 (TGCC/TGCC), indicating that the R486H does not measurably impact gamma-glutamyl carboxylase activity. The remaining two SNPs (2 and 5) are located within non-coding intron sequences. These 4 SNPs allowed for determining the genotype associated with the observed fatal coagulopathy. Screening for the premature truncation (SNP-4) based on the presence of a Bbv I restriction site in clinically normal lambs but not in the homozygous affected lambs allows for detection of the heterozygous state (GATT/GACC), because carrier animals are clinically normal.

Animals↗
PubMed2006

Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep.

A flock of Rambouillet sheep was examined because of increased lamb mortality caused by ineffective hemostasis at parturition. Neonatal-affected lambs presented with inadequate hemostasis at the umbilicus, pale mucus membranes, and markedly prolonged activated clotting time. Affected lambs had consistently prolonged 1-stage prothrombin times and activated partial thromboplastin times that supported a defect in the common pathway or defects in both the intrinsic and extrinsic pathway of the coagulation cascade. Decreased activity of vitamin K-dependent procoagulant factors II, VII, IX, and X in male and female lambs suggested either a defect of the hepatic enzyme gamma-glutamyl carboxylase, or vitamin K(1) 2,3 epoxide reductase. Affected lamb hepatic gamma-glutamyl carboxylase activity was markedly decreased compared with that of age- and sex-matched control lambs, while vitamin K(1) 2,3 epoxide reductase and glucose-6-phosphatase activities were similar between an affected and normal lamb. Subcutaneous vitamin K(1) supplementation did not increase vitamin K-dependent procoagulant factor activities in 3 lambs administered vitamin K(1) daily. These data confirm defective gamma-glutamyl carboxylase activity as the cause of impaired coagulation of sheep in this flock. This flock represents the only viable animal model of hereditarily defective gamma-glutamyl carboxylase activity.

Animals↗
PubMed2005

Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: implications for neuropathy severity.

Alterations in peripheral myelin protein 22 (PMP22) expression are associated with a heterogeneous group of hereditary demyelinating peripheral neuropathies. Two mutations at glycine 94, a single guanine insertion or deletion in PMP22, result in different reading frameshifts and, consequently, an extended G94fsX222 or a truncated G94fsX110 protein, respectively. Both of these autosomal dominant mutations alter the second half of PMP22 and yet are linked to clinical phenotypes with distinct severities. The G94fsX222 is associated with hereditary neuropathy with liability to pressure palsies, whereas G94fsX110 causes severe neuropathy diagnosed as Dejerine-Sottas disease or Charcot-Marie-Tooth disease type IA. To investigate the subcellular changes associated with the G94 frameshift mutations, we expressed epitope-tagged forms in primary rat Schwann cells. Biochemical and immunolabeling studies indicate that, unlike the wild-type protein, which is targeted for the plasma membrane, frameshift PMP22s are retained in the cell, prior to reaching the medial Golgi compartment. Similar to Wt-PMP22, both frameshift mutants are targeted for proteasomal degradation and accumulate in detergent-insoluble, ubiquitin-containing aggregates upon inhibition of this pathway. The extended frameshift PMP22 shows the ability to form spontaneous aggregates in the absence of proteasome inhibition. On the other hand, Schwann cells expressing the truncated protein proliferate at a significantly higher rate than Schwann cells expressing the wild-type or the extended PMP22. In summary, these results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy.

Animals↗
PubMed2003

Selectable marker-free transgenic barley producing a high level of cellulase (1,4-beta-glucanase) in developing grains.

The use of barley grains as bioreactors for high-level production of cellulase (1,4-beta-glucanase) was investigated. A hybrid cellulase gene, cel-hyb1, driven by the rice GluB-1 promoter was expressed specifically in developing endosperm. Codon usage optimisation of cel-hyb1 increased its expression in barley grains 527-fold and led to cellulase production of up to 1.5% of total grain protein. CEL-HYB1 enzyme in barley grains was highly stable during post-harvest storage. Selectable marker gene ( hph) was subsequently eliminated from transgenic lines through segregation of hph from synthetic cel-hyb1 ( syn.cel-hyb1) in T1 progeny, using a binary plasmid containing hph and syn.cel-hyb1 in separate T-DNAs. These data suggest that barley grains can potentially be used for the commercial production of cellulase.

Amino Acid Sequence↗
PubMed2003

Hemochromatosis secondary to repeated blood transfusions in a dog.

Hemochromatosis was presumptively diagnosed using cytologic examination of liver tissue from an aged male Miniature Schnauzer. The dog was presented after receiving whole blood transfusion every 6-8 weeks for 3 years to treat pure red cell aplasia. The cytologic specimen contained clusters of hepatocytes with abundant intracytoplasmic gold-yellow pigment granules and clumps of extracellular, green-black, globular pigment, both interpreted to be hemosiderin. Histologic sections of liver revealed hepatocellular degeneration with bridging portal fibrosis, lobular atrophy, biliary hyperplasia, and diffuse, severe hemosiderin accumulation. Serum iron and ferritin levels, and dry-weight iron concentrations of liver, heart, and kidneys were markedly increased. Hemosiderin accumulation was confirmed in hepatocytes of cytologic and histologic specimens using Perl's Prussian blue staining. This report is the first description of transfusional hemochromatosis in a dog and is the first to describe its cytologic appearance in a veterinary patient.

Animals↗
PubMed2001

Discovery of heterocyclic ureas as a new class of raf kinase inhibitors: identification of a second generation lead by a combinatorial chemistry approach.

Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as novel inhibitors of raf kinase, a key mediator in the ras signal transduction pathway. Structure-activity relationships were established, and the potency of the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54 microM) for a second generation series of heterocyclic urea raf kinase inhibitors.

Proto-Oncogene Proteins c-raf↗
PubMed2001

Putative uremic encephalopathy in horses: five cases (1978-1998).

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

Animals↗
PubMed2001

Detection of lymph node metastases in colorectal carcinoma.

The detection of lymph node metastases is the single most important prognostic factor for patients with colorectal cancer. This review outlines the difficulties and methods of detecting positive lymph node metastases in this disease. An outline of traditional diagnostic methods including preoperative ultrasound and cross sectional imaging techniques are evaluated alongside newer modalities including immunoscintography and PET scanning and intraoperative radioguided imaging. Pathological methods of detecting positive nodal disease using standard histopathological staging, enhanced lymph node harvesting and determination of micrometastases are also discussed.

Journal Article↗
PubMed2001

Beryllium Exposure Control Program at the Cardiff Atomic Weapons Establishment in the United Kingdom.

The Cardiff Atomic Weapons Establishment (AWE) plant, located in Cardiff, Wales, United Kingdom, used metallic beryllium in their beryllium facility during the years of operation 1961-1997. The beryllium production processes included melting and casting, powder production, pressing, machining, and heat and surface treatments. As part of Cardiff's industrial hygiene program, extensive area measurements and personal lapel measurements of airborne beryllium concentrations were collected for Cardiff workers over the 36-year period of operation. In addition to extensive air monitoring, the beryllium control program also utilized surface contamination controls, building design, engineering controls, worker controls, material controls, and medical surveillance. The electronic database includes 367,757 area sampling records at 101 locations and 217,681 personal lapel sampling records collected from 194 employees over the period 1981-1997. Similar workplace samples were collected from 1961 to 1980, but they were not analyzed because they were not available electronically. Annual personal mean sampling concentrations for all workers ranged from 0.11 to 0.72 micrograms per cubic meter (microg/m3) with 95th percentiles ranging from 0.22 to 1.89 microg/m3; foundry workers worked in the highest concentration areas with a mean of 0.87 microg/m3 and a 95th percentile of 2.9 microg/m3. Area sampling concentrations, as expected, were lower than personal sampling concentrations. Mean annual area sample concentrations for all locations ranged from 0.02 to 0.32 microg/m3. The area sample 95th percentile concentrations for all years were below 0.5 microg/m3. For the overwhelming majority of samples, airborne beryllium concentrations were below the 2.0 microg/m3 standard. Although blood lymphocyte testing for beryllium sensitization has not been routinely conducted among these workers, this metal beryllium processing facility is the only large scale beryllium facility of its kind to have experienced only one unique a case of clinical chronic beryllium disease (CBD) ascertained by traditional medical monitoring procedures. The treating physician determined that this lung disease was likely caused by a systems reaction resulting from a mound contaminated with beryllium. However, he could not rule out the potential for inhalation exposure. Over the 17 years of measurement data analyzed, on occasion, airborne beryllium concentrations have exceeded 2.0 microg/m3; however, the Cardiff experience demonstrates that strict and consistent adherence to exposure control measures that emphasized airborne and surface levels and appropriate engineering controls, work practices, and use of personal protective equipment appears to have successfully prevented the incidence of clinical CBD with the exception of one unique case.

Air Pollutants, Occupational↗
PubMed2001

A 10 year retrospective comparison of the diagnostic usefulness of synovial fluid and synovial biopsy examination.

BACKGROUND/AIMS: Synovial fluid examination is thought to be the pathological investigation of choice in most joint disorders, with only a few specific conditions necessitating biopsy, although no evidence based studies are available to support this belief. This study sought to investigate the validity of this assumption. METHODS: One hundred and three cases in which synovial fluid aspiration and synovial biopsy had both been performed at arthroscopy were studied. The amount of diagnostically useful information produced by each investigation was assessed. RESULTS: In most cases, both investigations provided the same amount of information and were generally equally specific or equally non-specific. Overall, the biopsy provided more information than the fluid in 29% of cases and vice versa in 18%. When only those cases in which both tests were adequate were considered, the biopsy provided more specific information than the fluid in a small number (9%) of cases, but these cases could not be predicted. CONCLUSION: The diagnostic usefulness of a biopsy approximates and occasionally exceeds that of a fluid. In the arthroscopic situation, the main advantage of performing both tests is that it provides a "failsafe mechanism" for the rare occasions when one of the samples is inadequate.

Arthritis↗
PubMed2001

Radiculomeningomyelitis due to Halicephalobus gingivalis in a horse.

An adult horse was euthanatized following a clinical diagnosis of cauda equina neuritis. Significant gross postmortem and histopathologic findings were limited to the sacral spinal cord and cauda equina. The sacral spinal cord, meninges, and spinal nerve roots were expanded and partially effaced by sclerosing granulomatous inflammation with necrosis. The lesion contained numerous nematode larvae and fewer adults with a rhabditiform esophagus having a corpus, isthmus, and valved bulb. Female nematodes were amphidelphic and didelphic with reflexed ovaries. These morphologic features confirm Halicephalobus gingivalis as a novel cause of clinical signs in this case of cauda equina neuritis.

Animals↗
PubMed2001

Feline leukemia virus in a captive bobcat.

An 11-mo-old captive-bred male neutered bobcat (Felis rufus) presented with lethargy, anorexia, leukopenia, neutropenia, lymphopenia, and nonregenerative anemia. The animal was diagnosed as feline leukemia virus (FeLV) positive by immunofluorescent antibody and enzyme-linked immunosorbant assay (ELISA) testing. It died despite supportive care. Pathologic examination revealed multifocal non-suppurative encephalitis, diffuse interstitial pneumonia, multifocal hepatocellular necrosis, non-suppurative peritonitis, and lymphoid depletion. FeLV was isolated from peripheral blood mononuclear cells, bone marrow, spleen, and lymph node. FeLV-specific gag sequences were amplified by DNA polymerase chain reaction (PCR) and aligned with known domestic cat FeLV's. The source of the virus was speculated to be a domestic cat that was a surrogate nurse. Case reports of FeLV in nondomestic felids are few, and FeLV does not appear to be enzootic in wild felids, except European wildcats (Felis silvestris) in France and Scotland. Introduction of FeLV into free-living and captive nondomestic felid populations could have serious consequences for their health and survival. Measures to prevent the introduction of this virus to nondomestic felids are warranted.

Animals↗
PubMed2000

Discovery of a new class of p38 kinase inhibitors.

The MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry effort and exhibit activity in the nanomolar range. Very steep structure-activity relationships are observed within this class.

Antirheumatic Agents↗
PubMed2000

1-Phenyl-5-pyrazolyl ureas: potent and selective p38 kinase inhibitors.

Inhibitors of the MAP kinase p38 are potentially useful for the treatment of arthritis and osteoporosis. Several 2,3-dichlorophenyl ureas were identified as small-molecule inhibitors of p38 by a combinatorial chemistry effort. Optimization for cellular potency led to the discovery of a new class of potent and selective p38 kinase inhibitors, exemplified by the 1-phenyl-5-pyrazolyl urea 7 (IC50 = 13 nM).

Antirheumatic Agents↗