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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 163 records · Page 9Linked to original sources
PubMed1999

Rab6 coordinates a novel Golgi to ER retrograde transport pathway in live cells.

We visualized a fluorescent-protein (FP) fusion to Rab6, a Golgi-associated GTPase, in conjunction with fluorescent secretory pathway markers. FP-Rab6 defined highly dynamic transport carriers (TCs) translocating from the Golgi to the cell periphery. FP-Rab6 TCs specifically accumulated a retrograde cargo, the wild-type Shiga toxin B-fragment (STB), during STB transport from the Golgi to the endoplasmic reticulum (ER). FP-Rab6 TCs associated intimately with the ER, and STB entered the ER via specialized peripheral regions that accumulated FP-Rab6. Microinjection of antibodies that block coatomer protein I (COPI) function inhibited trafficking of a KDEL-receptor FP-fusion, but not FP-Rab6. Additionally, markers of COPI-dependent recycling were excluded from FP-Rab6/STB TCs. Overexpression of Rab6:GDP (T27N mutant) using T7 vaccinia inhibited toxicity of Shiga holotoxin, but did not alter STB transport to the Golgi or Golgi morphology. Taken together, our results indicate Rab6 regulates a novel Golgi to ER transport pathway.

Animals↗
PubMed1999

Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide.

Airway epithelial cells are a rich source of eosinophil-selective C-C chemokines. We investigated whether cytokines and the topical glucocorticoid budesonide differentially regulate RANTES, monocyte chemoattractant protein-4 (MCP-4), and eotaxin mRNA and protein expression in the human bronchial epithelial cell line BEAS-2B and in primary human bronchial epithelial cells by Northern blot analysis and ELISAs. Eotaxin and MCP-4 mRNA expression induced by TNF-alpha alone or in combination with IFN-gamma was near-maximal after 1 h, peaked at 4 and 8 h, respectively, remained unchanged up to 24 h, and was protein synthesis independent. In contrast, RANTES mRNA was detectable only after 2 h and slowly increased to a peak at 24 h, and was protein synthesis dependent. Induction of eotaxin and MCP-4 mRNA showed a 10- to 100-fold greater sensitivity to TNF-alpha compared with RANTES mRNA. IL-4 and IFN-gamma had selective effects on chemokine expression; IL-4 selectively up-regulated the expression of eotaxin and MCP-4 and potentiated TNF-alpha-induced eotaxin, while IFN-gamma markedly potentiated only the TNF-alpha-induced expression of RANTES. Although budesonide inhibited the expression of chemokine mRNA to a variable extent, it effectively inhibited production of eotaxin and RANTES protein. Budesonide inhibited both RANTES- and eotaxin promoter-driven reporter gene activity. Budesonide also selectively accelerated the decay of eotaxin and MCP-4 mRNA. These results point to IL-4 as a possible mediator by which Th2 cells may induce selective production of C-C chemokines from epithelium and indicate that glucocorticoid inhibit chemokine expression through multiple mechanisms of action.

Administration, Topical↗
PubMed1999

Adamalysins. A family of metzincins including TNF-alpha converting enzyme (TACE).

The adamalysins are a family of proteins in the metzincin superfamily of metalloproteases, which also includes the matrix metalloproteinases. There are two subfamilies of adamalysins: the snake venom metalloproteases (SVMPs) and the ADAMs (proteins containing a disintegrin and metalloprotease domain). At least 23 ADAMs have been identified to date. The ADAMs are expressed by a wide variety of cell types, and are involved in functions as diverse as sperm-egg binding, myotube formation, neurogenesis, and proteolytic processing of cell surface proteins. An overview of the ADAM family and their functions will be presented. TACE is a unique member of the ADAM family that cleaves membrane-bound TNF-alpha to generate soluble TNF-alpha. Mice lacking proteolytically active TACE have been generated and characterized. The TACE knock-out results in perinatal lethality. Cells from the TACE-deficient mice release 80-90% less soluble TNF-alpha than do wild-type cells. Irradiated mice that are reconstituted with TACE knock-out hematopoeitic stem cells have markedly reduced levels of serum TNF-alpha following LPS challenge, compared to irradiated mice reconstituted with wild-type cells, suggesting that TACE is the major TNF-alpha converting enzyme in vivo. TACE-deficient cells are compromised in the generation of other soluble proteins that are produced as the result of cleavage of a membrane precursor form, suggesting that TACE is involved in multiple shedding events.

ADAM Proteins↗
PubMed1999

Soluble class I MHC with beta2-microglobulin covalently linked peptides: specific binding to a T cell hybridoma.

Soluble forms of the mouse MHC class I molecule, Dd, were produced in which the peptide binding groove was uniformly occupied by peptides attached via a covalent flexible peptide linker to the N terminus of the associated beta2-microglobulin. The MHC heavy chain and beta2-microglobulin were firmly associated, and the molecules displayed an Ab epitope requiring proper occupancy of the peptide binding groove. Soluble Dd containing a covalent version of a well-characterized Dd-binding peptide from HIV stimulated a T cell hybridoma specific for this combination. Furthermore, a tetravalent version of this molecule bound specifically with apparent high avidity to this hybridoma.

Amino Acid Sequence↗
PubMed1999

Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat.

Morphine maintenance doses of 10 mg kg(-1) day(-1), 20 mg kg(-1) day(-1) and 30 mg kg(-1) day(-1) were administered to three groups of rats via miniosmotic pumps for 7 days to induce physical dependence. They were then allowed to undergo spontaneous withdrawal. Radiotelemetric blood pressure measurements showed that morphine increased systolic and diastolic blood pressure on the first day of morphine treatment and produced a dose dependent decrease in heart rate, systolic and diastolic blood pressure thereafter. After the peak depressive effect, development of tolerance to morphine was observed in systolic and diastolic blood pressure, but not in the heart rate. During spontaneous withdrawal, both systolic and diastolic blood pressure increased beyond pre-morphine levels for all doses and there was a rebound increase in heart rate at the 30 mg kg(-1) day(-1) dose. These results suggest that the improved sensitivity of telemetric measures combined with the use of minipumps for morphine treatment provide an animal model of spontaneous opioid withdrawal.

Analgesics, Opioid↗
PubMed1999

Laparoscopy for diagnosis and staging of malignancy.

The use of minimally invasive surgery for abdominal pathology, including malignancy, has increased significantly within the past decade. Despite the advances in radiographic imaging, the use of laparoscopy for diagnosing and staging abdominal malignancy has become an important tool in the overall care of these patients. A review of published series for a variety of abdominal malignancies is presented. With the growing experience in this technique, some preliminary conclusions and ongoing issues are discussed.

Abdominal Neoplasms↗
PubMed1999

Characterizing complex chemosensors: information-theoretic analysis of olfactory systems.

The mechanisms that underlie a wine lover's ability to identify a favorite vintage and a dog's ability to track the scent of a lost child are still deep mysteries. Our understanding of these olfactory phenomena is confounded by the difficulty encountered when attempting to identify the parameters that define odor stimuli, by the broad tuning and variability of neurons in the olfactory pathway,and by the distributed nature of olfactory encoding. These issues pertain to both biological systems and to newly developed 'artificial noses' that seek to mimic these natural processes. Information theory, which quantifies explicitly the extent to which the state of one system (for example, the universe of all odors) relates to the state of another (for example, the responses of an odor-sensing device),can serve as a basis for analysing both natural and engineered odor sensors. This analytical approach can be used to explore the problems of defining stimulus dimensions, assessing strategies of neuronal processing, and examining the properties of biological systems that emerge from interactions among their complex components. It can also serve to optimize the design of artificial olfactory devices for a variety of applications, which include process control, medical diagnostics and the detection of explosives.

Animals↗
PubMed1999

Photobleaching GFP reveals protein dynamics inside live cells.

Cell biologists have used photobleaching to investigate the lateral mobility of fluorophores on the cell surface since the 1970s. Fusions of green fluorescent protein (GFP) to specific proteins extend photobleaching techniques to the investigation of protein dynamics within the cell, leading to renewed interest in photobleaching experiments. This article revisits general photobleaching concepts, reviews what can be learned from them and discusses applications illustrating the potential of photobleaching GFP fusion proteins inside living cells.

Animals↗
PubMed1999

Testing the association between residential fungus and health using ergosterol measures and cough recordings.

Questionnaire surveys in several countries have consistently detected an association between symptoms and residential mould growth. Confirmation by objective measures would strengthen the argument for causality. To address this issue, quantitative and qualitative fungal measures (airborne ergosterol and viable fungi in dust) were compared to respiratory symptoms (n = 403) and nocturnal cough recordings (n = 145) in Canadian elementary schoolchildren during the winter of 1993-1994. There was a 25 percent to 50 percent relative increase in symptom prevalence when mould was reported to be present (p < 0.05). However, neither symptoms nor recorded cough was related to objective measures of mould. In conclusion, the inability to find an association between objective measures of fungus and health suggest that either these objective measures, or the traditionally used questionnaire data are inaccurate. This discrepancy limits the acceptance of a causal relation between indoor fungal growth and illness.

Air Microbiology↗
PubMed1999

GABA(B) receptors function as heterodimers.

Our current understanding is that functional GABA(B) receptors exist as heterodimers of two related seven-transmembrane proteins, GABA(B)-R1 and GABA(B)-R2. GABA(B)-R1 requires GABA(B)-R2 to be expressed at the cell surface as a mature glycoprotein. Cloning of the GABA(B) receptor has failed to provide molecular evidence to support the existence of true receptor subtypes. The discovery of the heterodimeric nature of the GABA(B) receptor has already changed the way we think about GPCR function and it is likely that future studies will change our understanding about how receptor subtypes can be formed.

Animals↗
PubMed1999

The impact of clinical experiences during pre-registration diploma in nursing courses on initial career choice.

AIM: The aim of this study was to evaluate the impact of clinical learning experiences during the Pre-registration Diploma in Nursing (Adult) course on immediate career choice for qualifying nurses. BACKGROUND: Changes in nurse education has reduced the exposure of students to some client groups, particularly in critical care areas. In recent years trusts are experiencing difficulties in recruiting 'D' grade staff nurses to theatres and critical care units which may be a direct consequence of this change. METHODS: A questionnaire was distributed to 47 pre-registration adult branch students, followed by two focus group discussions using a sample of the same students. FINDINGS: Students appeared to use preconceived images and expectations about nursing which they relied on for job selection, unless changed by personal experience during their course. These students held generally negative images about theatre and critical care nursing, and as they had little experience to test these images during their training, the negative view remained dominant when choosing a job. CONCLUSION: A model describing these influencing factors on career decision making was developed. The discussion outlines some possible management solutions to address the problem of recruitment.

Adult↗