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Biomedical subjects

R Gilbert

Publications and source records attributed to R Gilbert.

At least 91 records · Page 5Linked to original sources
PubMed1994

Identification of a key integrin-binding sequence in VCAM-1 homologous to the LDV active site in fibronectin.

The integrin adhesion receptor alpha 4 beta 1 binds two ligands, the extracellular matrix glycoprotein fibronectin and the immunoglobulin superfamily member VCAM-1. Ligand-binding sites are contained with the HepII/IIICS domain of fibronectin, and within the homologous immunoglobulin domains 1 and 4 of VCAM-1. Previous studies have shown that the binding of each ligand to alpha 4 beta 1 is mutually exclusive, suggesting that they may employ similar mechanisms to bind receptor. Fibronectin contains at least three distinct peptide sequences that are active sites for alpha 4 beta 1 binding, two homologous sequences Leu-Asp-Val-Pro (LDVP) and Ile-Asp-Ala-Pro (IDAP), and a third related to Arg-Gly-Asp (RGD). Using a combination of site-directed mutagenesis and synthetic peptide approaches in conjunction with VCAM-1-dependent cell adhesion assays, we now report the identification of a key alpha 4 beta 1-binding sequence in both domains 1 and 4 of VCAM-1 as the tetrapeptide Ile-Asp-Ser-Pro (IDSP). Mutagenesis studies also suggest that an additional sequence in domain 1, KLEK, participates in receptor binding. Since IDSP is homologous to the LDVP and IDAP fibronectin peptides, this therefore provides a molecular explanation for the promiscuity of ligand binding by alpha 4 beta 1 and has implications for the design of synthetic VCAM-1 antagonists. The extrapolation of these findings to other integrin-binding immunoglobulin ligands is also discussed.

Amino Acid Sequence↗
PubMed1994

Day-night blood pressure variation in normotensive, normoalbuminuric type I diabetic subjects. Dippers and non-dippers.

OBJECTIVE: To examine day-night blood pressure (BP) variation in normotensive, normoalbuminuric subjects with type I diabetes and to assess the prevalence of an impaired nocturnal BP fall. RESEARCH DESIGN AND METHODS: Fourteen healthy volunteers and 13 normotensive, normoalbuminuric subjects with type I diabetes were studied with an ambulatory sphygmomanometric device for 24 h. RESULTS: No significant difference was found between diabetic and control groups with regard to daytime systolic blood pressure (sBP) or diastolic blood pressure (dBP). However, the mean nighttime sBPs (P < 0.01) and dBPs (P = 0.01) were significantly higher in the diabetic group compared with the control group. Furthermore, the night/day ratio for both sBP (P < 0.01) and dBP (P < 0.01) was significantly higher in the diabetic group. Approximately half of the diabetic subjects studied were non-dippers when defined either by a nocturnal fall in sBP/dBP of < 10/5 mmHg (5/13 vs. 0/14, P < 0.05: diabetic group vs. control group) or a day to night fall in either sBP (7/13 vs. 2/14, P < 0.05) or dBP (6/13 vs. 0/14, P < 0.01) of < 10%. CONCLUSIONS: Ambulatory BP may reveal impaired nocturnal BP fall in normotensive, normoalbuminuric subjects with type I diabetes. These subjects may be at greater risk of certain complications as a consequence of an increased BP burden.

Adult↗
PubMed1994

Strategic planning or muddling through? The relevance of the strategic planning process to the hospital sector.

We review some of the main themes in the literature about managerial strategy and strategic planning. Attention is paid to the limitations of strategic planning in the government sector generally and the public hospital system particularly. The alternative to strategic planning--to adapt a stance that is more pragmatic, incrementalist and iterative--is considered. A case study of a teaching hospital's approach to strategy over the last two years is used to provide an empirical complement to the literature analysis. We conclude that the rational planning approach has advantages over the adaptive, iterative approach through the information that it provides to hospital management about the strengths and weaknesses of the organisation.

Australia↗
PubMed1994

Survey of family physicians: what is their role in cancer patient care?

In 1993, a survey of randomly-selected family physicians in two regions of Ontario was conducted to assess their views on various aspects of supportive care of patients with cancer. A response rate of 71% was obtained. Results showed that physicians are using preventive and screening techniques in their practices. They are comfortable with most of their roles in supportive cancer care with the exceptions of conveying news of therapy failure and total coordination of care. There is significant dissatisfaction with certain aspects of the timing and content of the consultation letters received from the regional cancer centers. Finally, family physicians expressed the importance of their roles in palliative care.

Adult↗
PubMed1994

Detection of bovine leukocyte adhesion deficiency by nonisotopic ligase chain reaction.

A nonisotopic ligase chain reaction (LCR) assay was developed to detect the mutation (D128G; Shuster et al. (1992) PNAS 89, 9225-9) for bovine leukocyte adhesion deficiency (BLAD). Two sets of diagonally opposed discriminating LCR primers that differentiate the normal and BLAD allele were designed so that the 3' end of each primer overlapped the D128G mutation. These discriminating primers were synthesized with a 5' biotin and could be captured using streptavidin-coated microtitre wells. A common set of primers that abut these discriminating primers were also synthesized and 3'-tailed with digoxigenin-ddUTP. Captured LCR products were then detected using antidigoxigenin antibodies coupled to alkaline phosphatase. The assay readout was a chemiluminescent signal generated by the hydrolysis of Lumi-Phos 530 and the entire assay including DNA isolation can be completed within 8 h.

Animals↗
PubMed1993

Relationship of progressively increasing albuminuria to apoprotein(a) and blood pressure in type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetic patients.

This study has explored the temporal relationship between apoprotein(a), blood pressure and albuminuria over a mean interval of 11 years in a cohort of 107 diabetic patients of whom 26 (14 Type 2 (non-insulin-dependent), 12 Type 1 (insulin-dependent) had progressively increasing albuminuria ('progressors'). In Type 2 diabetic patients, no significant differences were noted for HbA1, blood pressure, creatinine clearance or serum lipids between progressors and non-progressors. In Type 1 diabetic patients, final systolic and diastolic blood pressures were higher in progressors compared with non-progressors and progressors showed impairment of renal function in association with a rise in blood pressure at the macroalbuminuric stage. Initial apoprotein(a) levels were similar in progressors and non-progressors of either diabetes type. Apoprotein(a) levels increased exponentially with time in 12 of 14 Type 2 progressors but only in 5 of 12 Type 1 progressors (p < 0.01). In Type 2 diabetic patients, the annual increase in apoprotein(a) levels was 9.1 +/- 2.4%, which was significantly greater than in non-progressors, 2.0 +/- 1.2% (p < 0.01) and also exceeded the rates of increase of apoprotein(a) in progressors with Type 1 diabetes, 4.0 +/- 1.4%, (p < 0.05). Apoprotein(a) levels correlated significantly with albuminuria in 8 of 14 Type 2 progressors but only in 3 of 12 Type 1 progressors (p < 0.05). The rate of increase of apoprotein(a) levels was not related to mean HbA1, creatinine or creatinine clearance levels, or to albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Immunoelectron microscopic localization of herpes simplex virus glycoprotein gB in the nuclear envelope of infected cells.

Herpesvirus, such as herpes simplex type 1 (HSV-1) acquire their envelope by budding through a modified inner membrane of the nuclear envelope which forms thick and dense patches at the site of budding. This suggests that some of the viral envelope glycoproteins must be transported to the nuclear envelope in order to be incorporated into the virus. In an effort to establish the localization of the HSV-1 glycoprotein gB-1 in the nuclear envelope of HSV-1 infected cells directly, we have studied the distribution of the glycoprotein gB-1 by immunoelectron microscopy using a polyclonal anti gB-1 antibody. A specific accumulation of gB-1 in the nuclear envelope, which was five times more labeled than the plasma membrane was observed. The glycoprotein gB-1 was localized in both the outer and the inner membrane of the nuclear envelope. The labeling over the nuclear envelope was distributed evenly and no preferential concentration of gB-1 around or within the patches where the virus buds was detected. The nucleocapsids were found to be labeled only when they become associated with the nuclear envelope indicating that gB-1 is incorporated into the virus at this site.

Animals↗
PubMed1993

Development of secondary hyperalgesia following non-painful thermal stimulation of the skin: a psychophysical study in man.

A psychophysical study has been carried out in 10 normal human subjects to examine whether conscious perception of pain is necessary for the development of secondary hyperalgesia. Prolonged thermal stimulation of the skin was applied to the subjects at intensities known to evoke discharges in polymodal nociceptors but insufficient to evoke pain sensations. During this stimulation the development of punctate and of stroking hyperalgesia was examined as was the presence of a skin flare indicative of nociceptor activation. All subjects developed a flare and an area of hyperalgesia following the application of the non-painful heat stimulus. The first change observed in the subjects was the appearance of an area of hyperalgesia to punctate stimuli, followed by flare and by stroking hyperalgesia. The onset of pain was always reported sometime after these events. Statistical analysis of these data for all subjects showed a highly significant difference between the time of onset of pain and the time of onset of any of the other 3 phenomena. Significant differences were also observed between the onset of punctate hyperalgesia and the onsets of flare and of stroking hyperalgesia. No difference was observed between the onset of flare and of stroking hyperalgesia. These results show that cutaneous hyperalgesia can be evoked in normal human subjects by prolonged thermal stimulation of the skin at temperatures that are not perceived as painful. The development of a flare in all subjects simultaneously with stroking hyperalgesia but before the perception of pain suggests that activation of nociceptors is necessary for the hyperalgesia to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Renal duplex Doppler ultrasound: an adjunct in the evaluation of hydronephrosis in the child.

We used renal duplex Doppler ultrasound to evaluate 28 hydronephrotic pediatric kidneys. A total of 28 normal renal units was used as controls. Renal Doppler ultrasound findings were compared with drainage values obtained with renal scintigraphic diuretic renography, and demonstrated close correlation. In control units significantly different resistive index values were noted between patients 0 to 12 months old and those older than 1 year. The younger group had average resistive indexes of 0.66, while the older group had an average value of 0.57 (p < 0.001). In hydronephrotic kidneys resistive index values were significantly higher (0.83) in renal units with obstructive T1/2 values on diuretic renography compared to those with indeterminate or nonobstructive T1/2 values (0.63) (p < 0.001). Renal Doppler ultrasound correlates closely with diuretic renography in hydronephrotic systems in infants and in older children. Additionally, it provides an early, noninvasive modality of assessing the dilated upper tract in infants and older children. Therefore, renal Doppler ultrasound is a reliable adjunct in identifying obstructed renal units.

Child↗
PubMed1993

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

Antibodies, Protozoan↗
PubMed1993

Dissociation of blood pressure and albuminuria in normal subjects infused with angiotensin II and noradrenaline.

1. Albuminuria is a predictor of diabetic renal disease and atherosclerosis. Changes in blood pressure (BP) may influence albuminuria. 2. The effect of acute BP elevation on albumin excretion rates (AER) using noradrenaline (NA) and angiotensin II (AII) infusions in six normal subjects was examined. 3. The average rise in BP during a 120 min infusion was 23 mmHg for AII and 16 mmHg for NA. 4. There was a marked dissociation between AER and BP levels in both AII and NA infusions. 5. Previously described correlations between BP and AER in ambulatory BP studies may be explained by other factors such as exercise and postural changes.

Adolescent↗
PubMed1993

Blue jay mania.

Explore the source record for details and available documents.

Adult↗
PubMed1992

A K+ current in Xenopus muscle cells which shows inactivation.

The purpose of this study was to describe an inactivating potassium current that is present in Xenopus muscle cells in culture. Whole cell currents were recorded from muscle cells grown in culture for 16-30 h. The majority of muscle cells had an outward current which inactivated during a 100 ms maintained depolarization. The outward current was reduced by tetraethylammonium or the aminopyridines, but not completely eliminated by either agent. Depolarizing prepulses reduced both the peak current and the late component of the current. The results suggest that by one day in culture these skeletal muscle cells develop an inactivating outward potassium current.

Animals↗
PubMed1992

Two classes of potassium currents in Xenopus muscle cells in young cultures.

The aim of the present study was to determine if both inactivating and non-inactivating potassium currents occur in skeletal muscle cells at early times in culture. Whole cell current was recorded from embryonic muscle cells within 4-10 h of plating. We found that in the cells which had an outward current, half had a current that did not inactivate and half had a current that inactivated during a maintained depolarization (100 ms). The two groups of cells did not differ in their age in culture or resting membrane potential. The results indicate that Xenopus skeletal muscle cells can acquire both types of outward potassium current early in culture life.

Animals↗
PubMed1992

Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death.

Three methods were used to investigate the role of infection in sudden unexpected infant death (SUD): (i) microbiological comparison of SUD victims and matched, live, community controls; (ii) postmortem classification of the contribution of infection to death; and (iii) case-control analysis of the relative risk associated with both infection and heavy wrapping. Limited sampling from the upper respiratory tract and gut in SUD victims and controls showed no significant excess of viral infection in the SUD victims (odds ratio = 1.98, 95% confidence interval (CI) 0.9 to 4.5). At postmortem examination, infection explained death in 3/95 babies and may have contributed to death in 37/95. Over 70 days of age, the combined presence of viral infection and wrapping in excess of 10 togs produced an odds ratio of SUD of 51.5 (95% CI 5.64 to 471.48) compared with wrapping of less than 6 togs. Viral infection was not a major risk factor as long as babies were lightly wrapped. In heavily wrapped babies the presence of a viral infection greatly increased the risk of SUD.

Bacterial Infections↗
PubMed1992

Health hazard of poorly regulated exposure during manufacture of cemented tungsten carbides and cobalt.

Forty two of 125 former workers in a factory in Syracuse, New York, which manufactured hard metal parts from tungsten carbide and cobalt, were studied by chest radiographs, spirometry, and plethysmographically determined lung volumes. The plant was closed in 1982 and the studies were performed in 1983-5. Recorded measurements of carbide dust concentrations were only mildly excessive by modern standards, but deceitful efforts to reduce the apparent concentration of dust were known to have occurred during an inspection by the Occupational Safety and Health Administration. Lung biopsies in four cases in the study and necropsy in one of the 83 cases not studied during life showed giant cell interstitial pneumonia and appreciable concentrations of tungsten carbide. This information indicates that exposure was substantial. Four workers had evidence of pulmonary fibrosis by chest radiographs; two of these workers had normal pulmonary function. Fourteen had abnormal pulmonary function, five of whom had a restrictive pattern, eight a pattern of air trapping, and one a combined pattern. Thus radiographic, or functional abnormalities, or both occurred in 16 of the 42 cases studied. No correlation with duration of exposure was established. Progressive clinically important disease (one fatal) has been found in four ex-workers, two in each of the restrictive and air trapping groups. These findings suggest that poorly regulated dust concentrations in a hard metals factory possibly cause pulmonary abnormalities and sometimes severe illness.

Adult↗
PubMed1992

A two-bag system for continuous measurement of oxygen uptake.

Collection of mixed expired gas in a bag has been a classic method for the estimation of VO2 during the steady state but has not been employed during unsteady state exercise in part because there is a need for suspending the acquisition of data during the period of gas analysis unless many bags are used. In this study a two-bag system is described in which one bag fills while the other is analyzed. Bag volume is under the control of the operator, and we employed volumes of 30 to 50 L. Thirty-one subjects were studied with this circuit in a progressive treadmill test. Although VO2 could be falsely elevated during periods of overbreathing, this source of error could be identified and its effect reduced if VO2 was plotted against both ventilation and power requirement. Plateau values of VO2 were identified only in six subjects and the ventilatory threshold in 16.

Adult↗