PubMed Health⌕ Search

Biomedical subjects

D J Paterson

Publications and source records attributed to D J Paterson.

At least 91 records · Page 5Linked to original sources
PubMed1990

Clinical applications of osseointegrated implants.

In the described seven case reports, the authors have demonstrated a number of varied applications of osseointegrated implant techniques including both removable and fixed prostheses. All patients had expressed dissatisfaction with previous prosthetic efforts to restore a satisfactory level of mastication or a desire to do away with removable oral prostheses. A high level of patient satisfaction was achieved through the application of implant techniques in these patients. Proper treatment planning must now include a consideration of implant dentistry as well as the previously available conventional alternatives for our edentulous and partially edentulous patients.

Adult↗
PubMed1989

Subsets of thymopoietic rat thymocytes defined by expression of the CD2 antigen and the MRC OX-22 determinant of the leukocyte-common antigen CD45.

The MRC OX-22 monoclonal antibody recognizes a restricted determinant of the rat leukocyte-common antigen (L-CA, CD45), which is expressed on most peripheral T cells and all B cells. In contrast only 2%-3% of thymocytes are OX-22+ and these are now shown to be mostly of the immature CD4-CD8- (double-negative, DN), phenotype with very few of the mature phenotype cells being OX-22+. Analysis of immunoperoxidase sections suggests that the DN OX-22+ cells are located in the cortex. Among the DN cells about 60% are OX-22+ and a similar percentage are positive for CD2 antigen. Double staining showed that OX-22+CD2-, OX-22+CD2+, and OX-22-CD2+ populations can be defined and that these three sets account for approximately 95% of the DN cells. Measurement of the thymopoietic activity of DN subsets showed that OX-22+CD2- and OX-22+CD2+ cells have regenerative capacity whilst OX-22-CD2+ cells do not.

Age Factors↗
PubMed1989

The ventilatory response to lowering potassium with dextrose and insulin in subjects with hyperkalaemia.

Arterial plasma potassium concentration ([ K+]a) is increased during exercise. This change is sufficient to excite arterial chemoreceptors and stimulate ventilation (VE) in the anaesthetized cat. Moreover, changes in [K+]a and VE are highly correlated during exercise, however the contribution that [K+]a makes to the control of breathing in man is not yet known. Four otherwise relatively healthy male hyperkalaemic renal patients had their VE measured before, during and after an intravenous infusion of dextrose and insulin to lower their [K+]a. Thirty-six minutes after the infusion began [K+]a had been reduced by ca. 2 mM. Ventilation was virtually unchanged throughout the experiment. These results suggest that [K+]a does not significantly affect VE in this group of subjects. The assumptions that would need to be made to extrapolate this conclusion to the general population are discussed.

Adult↗
PubMed1989

Changes in arterial plasma potassium and ventilation during exercise in man.

We have investigated the relationship between arterial plasma potassium ( [K+]a) and ventilation (VE) in man because hyperkalaemia has been shown to increase VE in the anaesthetized cat by direct stimulation of the arterial chemoreceptors. Six healthy male volunteers undertook about of sub-maximal (100 W) and maximal (sprint ca. 350 W) exercise on a cycle ergometer. VE was measured breath-by-breath and arterial blood was sampled at regular intervals from a catheter inserted into a brachial artery for measurement of [K+]a and base excess. Changes in [K+]a closely mirrored changes in VE during exercise and recovery. At 100 W [K+]a increased from 4 mM to 5 mM, and during the sprint [K+]a increased to ca. 7 mM. Base excess did not mirror VE in that it reached its nadir 1-3 min after exercise had stopped, when [K+]a and VE were both falling. The increases in [K+]a seen here are probably sufficient to enhance the arterial chemoreceptor drive during exercise. Furthermore, the close temporal relationship between [K+]a and VE suggests that it is possible that exercise hyperkalaemia may contribute to the control of breathing in exercise.

Arteries↗
PubMed1989

Tolbutamide reverses hypoxic pulmonary vasoconstriction in isolated rat lungs.

We have investigated the effects of tolbutamide on the hypoxic vasoconstriction of isolated, perfused rat lungs. We did this because lowered ATP may link hypoxia and constriction, and tolbutamide mimics the effects of ATP in other tissues by blocking ATP-sensitive potassium (ATP-K) channels. Pulmonary vasoconstriction, induced by lowering the oxygen of the gas ventilating the lungs from 95 to 2%, was always reduced or abolished by tolbutamide (1.7 x 10(-4)-8.5 x 10(-3) M). High concentrations (greater than or equal to 10(-3) M) of diazoxide, a drug that opens ATP-K channels, dramatically constricted the pulmonary vasculature and this effect was also reversed by tolbutamide. The opening of ATP-K channels may therefore underlie hypoxic pulmonary vasoconstriction.

Adenosine Triphosphate↗
PubMed1988

Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies.

Rat T cells and thymocytes were induced to proliferate by a pair of mAbs, MRC OX-54 and MRC OX-55, directed against rat CD2. Accessory cells were required but their role was not simply for crosslinking of the two mAbs, as neither MRC OX-54 nor MRC OX-55 alone, in the presence of a crosslinking second antibody, caused T cell mitogenesis. Nor could the phorbol ester PMA replace either antibody. The two mAbs recognized distinct epitopes on rat CD2; however, MRC OX-54 could partially block MRC OX-55 binding whereas the reverse situation was not seen. A further CD2 epitope was recognized by two mutually competitive mAbs, MRC OX-34 and MRC OX-53, which were not mitogenic. Neither MRC OX-34 nor MRC OX-53 affected the binding of MRC OX-54 or MRC OX-55, yet they prevented the mitogenic effect induced by these mAbs. The presence of mAbs against CD4 and the IL-2-R also abrogated this mitogenesis, whereas an anti-CD5 mAb augmented the CD2-induced proliferation.

Animals↗
PubMed1988

The effect of beta adrenergic blockade on the carotid body response to hyperkalaemia in the cat.

Arterial chemoreceptor discharge and ventilation are both significantly increased when the concentration of arterial potassium is raised to a level typical of moderate exercise. However, although the plasma potassium level of exercising, beta-blocked patients rises by more than that of normal subjects, this does not show up in their steady-state ventilatory response, i.e. exercising beta-blocked subjects ventilate no more than exercising controls. The present experiments were designed to test the hypothesis that the apparent failure of beta-blocked subjects to respond to the extra hyperkalaemia that they experience might be accounted for by a reduction in the sensitivity of arterial chemoreceptors to potassium. We used eleven pentobarbitone-anaesthetized, thoracotomized, artificially hyperventilated cats, in which arterial potassium was raised from ca. 4.5 to ca. 7 mM before and during beta blockade by propranolol or atenolol. The steady-state relation between chemoreceptor discharge and arterial potassium was curvilinear, discharge becoming more sensitive to potassium as the concentration of the latter was raised. Beta blockade significantly reduced discharge at all levels of plasma potassium (P less than 0.0001). It also significantly reduced (P less than 0.05) the slope of the response of discharge to a given increase of plasma potassium. Our results show that beta blockade decreases the sensitivity of arterial chemoreceptors to increases in arterial potassium. This may explain why exercising beta-blocked subjects breathe no harder than controls, in spite of the fact that they are more hyperkalaemic.

Animals↗
PubMed1988

The effect of hypoxia on plasma potassium concentration and the excitation of arterial chemoreceptors in the cat.

Intra-arterial recordings of potassium concentration ([K+]a) and arterial chemoreceptor discharge were made in six anaesthetized cats while tracheal PO2 was stepped every 2 min (end-tidal PO2 ca. 140, 60, 40 and 95 Torr) at constant PCO2 (33 Torr). [K+]a increased hyperbolically from 3.0 mM to 4.5 mM as arterial PO2 was lowered from 95 to 40 Torr. Because the discharge of arterial chemoreceptors is excited by hyperkalaemia as well as hypoxia, the hypoxic discharge of arterial chemoreceptors may have a component mediated by [K+]a. The mechanisms underlying the arterial K+ increase in hypoxia remain unknown.

Action Potentials↗
PubMed1988

Effects of potassium, oxygen and carbon dioxide on the steady-state discharge of cat carotid body chemoreceptors.

1. We have studied the effects of intravenous infusions of 0.1 mmol/min KCl (raising arterial potassium from ca. 3.2 to 6.0 mM) on the steady-state responses of carotid body chemoreceptors to end-tidal PCO2 and PO2 in the pentobarbitone-anaesthetized cat. 2. The excitatory effect of these KCl infusions was enhanced by hypoxia and reduced or abolished by hyperoxia. 3. Hypercapnia did not enhance, and usually reduced, excitation by KCl. 4. When similar control discharge frequencies were established by hypoxia or by hypercapnia, a KCl infusion excited the hypoxic discharge by about twice as much as it did the hypercapnic discharge. 5. These observations are not inconsistent with the idea that the mechanism underlying hypoxic excitation of arterial chemoreceptors is one that controls extracellular potassium concentration near the afferent nerve ending. 6. Insofar as potassium-induced excitation of chemoreceptor discharge is abruptly reduced by hyperoxia it behaves like Asmussen and Nielsen's postulated 'anaerobic work substance' and it may therefore contribute to the increased importance of the arterial chemoreflex reported in exercise.

Action Potentials↗
PubMed1987

Similarities in sequences and cellular expression between rat CD2 and CD4 antigens.

The MRC OX-34 antigen of rat T lymphocytes was purified and peptide sequences were obtained. Oligonucleotide probes were synthesized and cDNA clones coding for the antigen were isolated and sequenced to yield a predicted protein sequence for the molecule that fitted the peptide data. Comparison of this sequence with that for human CD2 determined by Sewell et al. showed that OX-34 is rat CD2. The primary structure of the molecule was notable for a moderately large cytoplasmic domain of unusual sequence and also for its highly significant relationship to CD4 antigen in the membrane proximal extracellular region and the transmembrane sequence. A relationship to the Ig superfamily can be argued for the two extra cellular domains of CD2, even though neither fits the standard pattern for Ig-related domains. Within the T lymphocyte lineage, rat CD2 seemed to be present on all stages with the exception of approximately 50% of the thymic CD4-,CD8- cells. In addition, the antigen was prominent on most macrophages in the spleen but not found on peritoneal or liver macrophages. CD4 antigen is also expressed on T lymphocytes and macrophages, and thus CD2 and CD4 appear similar in their cellular expression as well as structural characteristics.

Amino Acid Sequence↗
PubMed1987

The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes.

A monoclonal antibody called MRC OX-44 is described that labels all myeloid cells and peripheral lymphoid cells but only 12% of thymocytes. The OX-44+ thymic cells include most if not all cells found in the medulla but only a small fraction of the cortical cells. Together with CD4 and CD8 antigens, seven subsets of thymic cell were defined and it was notable that most CD4- CD8- cells were OX-44+ whereas almost all CD4+ CD8+ cells were OX-44-. In functional tests, the OX-44+ cells accounted for all proliferation by thymocytes when stimulated by allogeneic spleen cells or concanavalin A plus growth factors and OX-44- cells were completely negative in these assays. Also, in tests for thymopoiesis after intra-thymic injection of cells, all activity was OX-44+. It seems possible that the OX-44+ set may include all functionally relevant cells in the rat thymus.

Animals↗
PubMed1987

Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts.

Mouse monoclonal antibodies (MAbs) have been prepared against rat T cell blasts. One MAb called MRC OX-40 recognized an antigen that differed from any previously described in that its expression was detected only on T blasts that also expressed the CD4 antigen. The OX-40 MAb did not detect an activation determinant of CD2 or CD4 molecules but recognized a distinct chain of mol. wt 50,000. The OX-40 MAb augmented T cell proliferation at late stages on in vitro responses. Other MAbs without obvious counterparts in other species were MRC OX-48 and MRC OX-49,50 which recognized cell surface molecules of mol. wts of about 95,000 and 90,000, respectively. The OX-48 antigen was not expressed on resting lymphocytes but was found on a subset of T and B blasts and also on other leucocytes. The OX-49,50 antigen was found on most haemopoietic cells but was expressed at greatly increased levels after lymphocyte activation and this was also the case for MRC OX-47 antigen which is of unknown Mr. The MRC OX-39 MAb was found to bind the rat IL-2 receptor; expression of this antigen was detected on thymic dendritic cells as well as on T blasts. The phenotype of rat T blasts compared to resting cells was also examined and changes in expression of L-CA, Thy-1, OX-2 and CD8 antigens were seen in addition to the changes found with the above MAbs.

Animals↗
PubMed1987

Entrainment of respiratory frequency to exercise rhythm during hypoxia.

Breathing frequency (f) is often reported as having an integer-multiple relationship to limb movement (entrainment) during rhythmic exercise. To investigate the strength of this coupling while running under hypoxic conditions, two male Caucasians and four male Nepalese porters were tested in the Annapurna region of the Himalayas at altitudes of 915, 2,135, 3,200, 4,420, and 5,030 m. In an additional study in a laboratory at sea level, three male and four female subjects inspired various O2-N2 mixtures [fraction of inspired O2 (FIO2) = 20.93, 17.39, 14.40, 11.81%] that were administered in a single-blind randomized fashion during a treadmill run (40% FIO2 maximum O2 consumption). Breathing and gait signals were stored on FM tape and later processed on a PDP 11/73 computer. The subharmonic relationships between these signals were determined from Fourier analysis (power spectrum), and the coincidence of coupling occurrence was statistically modeled. Entrainment decreased linearly during increasing hypoxia (P less than 0.01). Moreover, a significant linear increase in f occurred during hypoxia (P less than 0.05), whereas stride frequency and metabolic rate remained constant, suggesting that hypoxic-induced increases in f decreased the degree of entrainment.

Adult↗
PubMed1987

Maximal exercise cardiorespiratory responses of men and women during acute exposure to hypoxia.

Three male and four female subjects were acutely exposed to normoxic and hypoxic gas mixtures (FIO2 = 17.39%, 14.40%, 11.81%) in a single-blind randomized fashion during four treadmill runs to volitional exhaustion. Maximal scores for oxygen consumption (VO2), carbon dioxide production and heart rate decreased linearly (p less than 0.01) with increasing hypoxia. Conversely, maximal scores for ventilation, ventilatory equivalent (VE/VO2) and R increased linearly (p less than 0.01) with decreasing FIO2. During hypoxia, no significant differences in work time or respiratory compensation threshold were evident. However, female subjects had significantly higher (p less than 0.05) VE/VO2 scores and showed a relative decrease in VO2max that was significantly less (p less than 0.01) than male subjects. It was concluded that young highly active females, when compared to males of similar age and relative condition, have a stronger adaptive response to acute hypoxia during a maximal treadmill run.

Acute Disease↗
PubMed1986

The entrainment of ventilation frequency to exercise rhythm.

To investigate whether ventilation frequency could be entrained to a sub-harmonic of the exercise rhythm, 19 experimentally naive male volunteers were tested during steady state bicycle ergometry and arm cranking under conditions of constant applied workload. Each exercise was performed at two separate ventilatory loads, one within the linear range and the other in the curvilinear range of ventilatory response to exercise. A preferred exercise rhythm was initially adopted (4 min.) followed by forced incremented and decremented rhythm changes each lasting 3 min during a 12 min exercise period. Ventilation, pedal pulse train and heart rate were sampled at 17 Hz on a PDP 11/23 computer. Ratios of limb frequency to dominant respiratory frequency were determined following Fourier analysis of these signals. Data that lay within +/- 0.05 of an integer and half-integer ratio were accepted as indices of entrainment, provided that the observed entrained scores were statistically significant. Ventilation frequency showed a clear, but intermittent tendency to entrain with limb frequency. This tendency was greater during bicycle ergometry, possibly as a consequence of task familiarisation, although both exercise entrainments were independent of workload. No difference between preferred versus varied exercise rhythm was evident, but more entrainment (p less than 0.01) was observed during a decremental change in exercise rhythm. These responses do not appear to support an appreciable role for limb-based afferents in the control of entrainment. The results of this study provide evidence that exercise rhythm has some regulatory role in the control of breathing during moderate rhythmical laboratory-based exercise ergometry.

Adult↗
PubMed1986

Monoclonal antibodies against a rat leucocyte antigen block antigen-induced T-cell responses via an effect on accessory cells.

The MRC OX-45 and OX-46 mouse monoclonal antibodies recognize a rat cell surface glycoprotein of 45,000 MW that is present on a wide variety of haematopoietic cells and on endothelial cells. MRC OX-45 IgG or F(ab')2 blocked the primary mixed lymphocyte response (MLR) and the secondary response of T lymphocytes to the soluble antigen DNP-BGG. In contrast, the antibodies had no effect on the cytotoxic activity of specific (CTL) or non-specific (NK) killer cells or on proliferative responses stimulated by lectins or oxidative mitogenesis. The inhibitory effect was at the level of stimulator cells rather than responders since mouse anti-rat xenogeneic MLRs were inhibited but rat anti-mouse responses were unaffected. However, the effect was not a direct one because inhibition was seen when irradiated spleen cells were used as stimulators but not when cell populations highly enriched for dendritic cells were used. In the latter case, inhibition potentiated by antibody could be restored if a peritoneal cell population enriched for macrophages was added back to the cultures. The inhibitory effects of these monoclonal antibodies seem most likely to be due to potentiation of nonspecific suppression by macrophages.

Animals↗