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Biomedical subjects

G Fox

Publications and source records attributed to G Fox.

At least 37 records · Page 2Linked to original sources

The cell attachment site on foot-and-mouth disease virus includes the amino acid sequence RGD (arginine-glycine-aspartic acid).

The amino acid sequence RGD (arginine-glycine-aspartic acid) is highly conserved in the VP1 protein of foot-and-mouth disease virus (FMDV), despite being situated in the immunodominant hypervariable region between amino acids 135 and 160. RGD-containing proteins are known to be important in promoting cell attachment in several different systems, and we report here that synthetic peptides containing this sequence are able to inhibit attachment of the virus to baby hamster kidney (BHK) cells. Inhibition was dose-dependent and could be reversed on removal of the peptide. A synthetic peptide corresponding to a portion of the same hypervariable region but not containing the RGD sequence did not inhibit virus attachment under the same conditions. Antibody against the RGD region of VP1 blocked attachment of the virus to BHK cells, and neutralizing monoclonal antibodies, which neutralize virus by preventing cell attachment, were blocked by RGD-containing peptides from binding virus in an ELISA test. Cleavage of the C-terminal region of virus VP1 in situ with proteolytic enzymes reduced cell attachment, and antiserum against a peptide corresponding to this region was also able to inhibit attachment of virus to BHK cells. These results indicate that the amino acid sequence RGD at positions 145 to 147 and amino acids from the C-terminal region of VP1 (positions 203 to 213) contribute to the cell attachment site on FMDV for BHK cells.

Amino Acid Sequence

Cost of neonatal intensive and special care.

A detailed costing of neonatal intensive and special care was made for the year 1986 at the Rotunda Hospital. Cost was expressed at 1986 prices in punts. There was 1,364 admissions including external transfers giving a total of 10,086 bed days, divided into 1,044 intensive care and 9,042 special care bed days. The total cost of intensive and special care was 1,342,500 pounds. Costs per inpatient day were 288 pounds for intensive and 115 pounds for special care. Sixty percent of the intensive care bed days were used by infants weighting less than 1,500 g birth weight and 93% by infants less than 2,500 g birth weight; this emphasizes the effect of population mix on resource use. The average cost of intensive care survivors by birth weight were: less than 1,000 g - 16,226 pounds (8,052 pounds-23,535 pounds); 1,000 g-1,499 g - 13,412 pounds (1,898 pounds-22,456 pounds); 1,500 g-2,499 g - 8,864 pounds (633 pounds-17,666 pounds); 2,500 g + - 5,123 pounds (384 pounds-12,636 pounds). The average cost of all admissions to special or intensive care was 984.24 pounds. Using this figure (984.24 pounds) and assuming that 13% of all births in 1986 required special or intensive care the total health care expenditure on neonatal special or intensive care in 1986 amounts to 8.03 million pounds of a total Department of Health budget of 1,269 million pounds. By allocating infants to the currently used neonatal diagnostic related groupings (DRGs) and assigning costs at 1987 US reimbursement levels, the total cost to the Rotunda would be 1,878,750 pounds punts. The current level of DRGs derived from the reimbursement rates in the United States which is insufficient to meet the actual cost incurred there, is 40% greater than current total funding of neonatal intensive and special care in the Rotunda. Current funding levels in the United Kingdom are 13% to 80% greater than in the Rotunda.

Costs and Cost Analysis

Crystallization and preliminary X-ray diffraction analysis of foot-and-mouth disease virus.

Foot-and-mouth disease virus has been crystallized with the objectives of (1) determining the composition and conformation of the major immunogenic site(s) and (2) comparing its structure with those of the related polio, rhino and Mengo viruses, representing the other three genera of the picornaviruses. Most of the work has been done with virus strain O1BFS 1860, which crystallized as small rhombic dodecahedra of maximum dimension 0.3 mm. Virus recovered from crystals was infectious, and was indistinguishable from native virus both in protein composition and buoyant density. The stability of the crystals in the X-ray beam was comparable with that of other picornavirus crystals and they diffracted to a resolution of better than 2.3 A. Initial analysis of the X-ray diffraction data shows the virus to be positioned on a point of 23 symmetry in a close-packed array so that examples of all the icosahedral symmetry elements, except the 5-fold axes, are expressed crystallographically. The cell dimensions are a = b = c = 345 A, alpha = beta = gamma = 90 degrees, with a space group of I23. The diameter of the virus particle is 300 A. Despite the small size of the crystals, diffraction data have been collected to a reasonable resolution using a synchrotron source. Phasing of the diffraction data will be attempted using the methods of molecular replacement.

Aphthovirus

Mechanical aspects of chest wall distortion.

During passive inflation of the respiratory system, the rib cage (RC) expands because the pressure applied to it [approximately equal to abdominal pressure (Pab)] increases. Similar Pab-tidal volume (VT) relationships between passive and spontaneous inspirations would occur only if 1) Pab acts on RC equally in the two situations (no distortion) or 2) the extradiaphragmatic inspiratory muscles expand RC, compensating for distortion. In anesthetized adult rats and in sleeping human infants the passive relationships between VT and Pab or abdomen motion (AB) were constructed by occluding the airways during expiration. For a given Pab (or AB) in active breathing VT averaged 55% (rats) and 49% (infants) of the passive volume change. With phrenic stimulation in rats VT was only slightly less than during spontaneous breathing, indicating that, in the latter case, the respiratory system was essentially driven only by the diaphragm. In both species occasional breaths with large RC expansion occurred, and VT was then equal to or larger than the passive volume at iso-Pab. We conclude that 1) RC distortion decreases VT to approximately half of the passive value and 2) being on the relaxation curve reflects "compensated" distortion and not absence of it.

Abdomen

Thrombin stimulates Na+-H+ exchange across the human platelet plasma membrane.

We have investigated the release of protons from thrombin-stimulated platelets. Addition of thrombin to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.1 mM amiloride, a potent inhibitor of the Na+/H+ transport system, the amount of protons liberated was decreased by about 50%, and was further reduced to about 15% by 1 mM amiloride. Similar inhibition of H+ release was observed after Na+ in the incubating medium had been replaced by choline. We conclude that one of the earliest events in thrombin-stimulated platelets consists of the activation of an Na+/H+ countertransport, which leads to an increase in intracellular pH.

Amiloride

The effect of carbonic anhydrase inhibition on the velocity of thrombin-stimulated platelet aggregation under physiological conditions.

We have studied the effect of ethoxzolamide , a specific carbonic anhydrase inhibitor, on the velocity of thrombin-stimulated platelet aggregation. After preincubation of platelet rich plasma with 10(-6) M ethoxzolamide the velocity of platelet aggregation was reduced by about 40%. Between 10(-11) M and 10(-10)M ethoxzolamide was necessary to achieve a half-maximal diminution of the aggregation velocity. An identical maximal reduction of the velocity of aggregation as with ethoxzolamide could be achieved by a nearly complete removal of CO2 from the platelet rich plasma. These results suggest that the intracellular CO2 hydration-dehydration reaction is involved in the activation of human platelets by thrombin. It is possible that the cytosolic carbonic anhydrase of platelets provides a rapid source of the protons that are transferred across the plasma membrane during the activation process.

Blood Platelets

Muscle pressure and flow during expiration in infants.

The postinspiratory activity of the inspiratory muscles (Pmusl) was estimated in 12 infants (2 to 4 days old) by analysis of the rise in mask pressure after airway occlusion at end inspiration. We reasoned that if at the end of inspiration Pmusl instantaneously ceased, the mask pressure would immediately increase to the relaxation pressure value corresponding to that volume. Any delay would suggest some degree of Pmusl. In 9 infants, Pmusl reached zero before the end of an average expiration (TE), although lasting for a long portion of TE (83% +/- 25 SD). We then compared the expiratory tidal flow-volume curves during resting breathing with the curves of "relaxed" expirations. In general, the tidal curve shows a linear portion that can be extrapolated to zero flow. From this extrapolation it is apparent that the end-expiratory level (FRC) is above the resting volume of the respiratory system (Vr), the FRC-Vr difference averaging 3.11 ml/kg. In 6 infants, the tidal expiratory flow-volume curve was displaced to the left of the "relaxed" curve, whereas in the remaining infants the two curves superimposed. These analyses suggest that in infants during tidal breathing (1) Pmusl can substantially contribute to the rise in FRC, and (2) the final portion of expiration is in most cases "relaxed." In some infants, however, a braking mechanism, probably of laryngeal origin, further decreases the expiratory flow and may contribute in maintaining the mean lung volume elevated.

Functional Residual Capacity

Effect of morphine on the hypothalamic-pituitary axis in postmenopausal women.

In this study, 10 postmenopausal women were given 5 mg of morphine intravenously; and the serum level of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and growth hormone (GH) were measured before and after morphine injection. A significant increase in serum prolactin as well as a significant decrease in LH were observed following the administration of morphine. It is suggested that morphine may affect a common neurotransmitter that controls both prolactin and LH secretion. It is also of interest that the increase in serum prolactin following morphine injection is of similar magnitude as observed in premenopausal patients.

Female

Dynamics of breathing in infants.

Passive compliance (C) has been measured in 10 infants at 10--90 min after birth and in 10 infants at a few days of life by recording mouth pressure after airways occlusions at end inspiration. From the slope of the expiratory flow-volume curve, the passive time constant (tau) and resistance (R = tau/C) have been also computed. Examination of the changes of C with time and of the expiratory flow-volume curves indicates that the end-expiratory volume is maintained above functional residual capacity at both ages, but significantly more so at a few days (7.6 ml) than at 10--90 min (3.5 ml). The passive time constant (tau = C . R) is shorter at the early age due to the smaller C. The active compliance (C') and resistance (R') values have been estimated from the pressure generated by the infant when the airways are occluded at end expiration. The active time constant of the respiratory system (tau' = C' . R') is less than tau, due to a smaller active compliance, particularly at a few days. The active resistance is on the contrary similar to R. The active stiffening of the respiratory system provides more stability of the infant's respiratory system and a more ready volume response for any given change in pressure; its price, however, is a higher work of breathing. At optimal breathing rates, in fact, the active work is 127% (10--90 min) to 183% (a few days) higher than that computed from the passive values. The inspiratory flow wave tends to be squared at both ages minimizing the energy losses due to friction.

Airway Resistance

[Baker's eczema through chromium compound in flour (author's transl)].

In several former papers on baker's eczema authors happened to hint at hypersensitivity to chromium in bakers suffering from eczema. To our knowledge however the question, if there is any connection between chromium-hypersensitivity and a baker's occupation, has not been investigated later on. In a baker with eczema of the hands relapses occurred obviously as a consequence of exclusive contact to flour, only hypersensitivity to chromium was revealed. Thus 4 sorts of flour used in GDR were analysed. Chromium content ranged between 0.01 and 0.09 mg%. It may be concluded, that even those comparatively low chromium levels are capable of giving rise to eczema.

Chromium