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Biomedical subjects

P Doherty

Publications and source records attributed to P Doherty.

At least 145 records · Page 8Linked to original sources
PubMed1985

111Indium-labelled lymphocytes do not image or label the pancreas of the BB/W rat.

Autologous transfusions of 111indium-labelled peripheral blood lymphocytes reportedly image the pancreas of patients with Type 1 (insulin-dependent) diabetes at the time of onset. We attempted to apply this technique to the spontaneously diabetic BB/W rat. First, acutely diabetic BB/W rats, diabetes-prone BB/W rats, diabetes-resistant W-line BB/W rats, and Wistar Furth rats were given autologous transfusions of labelled peripheral blood lymphocytes. Radioactivity recovered from the pancreas was similar in all groups. No correlation was found between the intensity of imaging and the presence or intensity of insulitis. To decrease non-specific intravascular radioactivity, acutely diabetic, diabetes-prone, and W-line rats were perfused 48 h after autologous transfusion of labelled lymphocytes. Again, the intensity of recovered activity was similar in all groups, using both macroautoradiography and numerical counting techniques. A second set of experiments studied diabetes and insulitis induced by passive transfer of concanavalin A-treated splenic lymphocytes from acutely diabetic donors. Activated lymphocytes were labelled with 111Indium and given to groups of diabetes-prone and diabetes-resistant rats. There were no differences in pancreatic localization 72-96 h after injection. Groups of diabetes-prone and diabetes-resistant rats were also given concanavalin A-activated lymphocytes and then challenged 2-10 days later with autologous transfusions of labelled peripheral blood lymphocytes. Again, no differences in organ labelling or imaging were detected. We conclude that the autologous transfusions of 111indium-labelled lymphocytes do not label or image the pancreas of the BB/W rat.

Acute Disease↗
PubMed1985

Pulse oximetry in pediatric intensive care: comparison with measured saturations and transcutaneous oxygen tension.

We evaluated a new pulse oximeter designed to monitor beat-to-beat arterial oxygen saturation (SaO2) and compared the monitored SaO2 with arterial samples measured by co-oximetry. In 40 critically ill children (112 data sets) with a mean age of 3.9 years (range 1 day to 19 years), SaO2 ranged from 57% to 100%, and PaO2 from 27 to 128 mm Hg, heart rates from 85 to 210 beats per minute, hematocrit from 20% to 67%, and fetal hemoglobin levels from 1.3% to 60%; peripheral temperatures varied between 26.5 degrees and 36.5 degrees C. Linear correlation analysis revealed a good agreement between simultaneous pulse oximeter values and both directly measured SaO2 (r = 0.95) and that calculated from measured arterial PaO2 (r = 0.95). The device detected several otherwise unrecognized drops in SaO2 but failed to function in four patients with poor peripheral perfusion secondary to low cardiac output. Simultaneous measurements with a tcPO2 electrode showed a similarly good correlation with PaO22 (r = 0.91), but the differences between the two measurements were much wider (mean 7.1 +/- 10.3 mm Hg, range -14 to +49 mm Hg) than the differences between pulse oximeter SaO2 and measured SaO2 (1.5% +/- 3.5%, range -7.5% to -9%) and were not predictable. We conclude that pulse oximetry is a reliable and accurate noninvasive device for measuring saturation, which because of its rapid response time may be an important advance in monitoring changes in oxygenation and guiding oxygen therapy.

Adolescent↗
PubMed1985

Ganglioside GM1 does not initiate, but enhances neurite regeneration of nerve growth factor-dependent sensory neurones.

An enzyme-linked immunoadsorbent assay (ELISA) for neurofilament protein was utilised to quantify the effect of exogenous ganglioside on neurite regeneration in cultures of dorsal root ganglion neurones. In contrast to nerve growth factor (NGF), ganglioside GM1 (100 micrograms/ml) failed to support neuronal survival and neurite regeneration as quantified by the ELISA assay and confirmed by morphological criteria. However, the simultaneous presence of GM1 (100 micrograms/ml) and NGF (0.5-5 ng/ml) throughout a 5-day period of culture resulted in an enhancement of previously reported NGF-induced increases in the expression of neurofilament protein. Further, the addition of GM1 (0-200 micrograms/ml) at 48 h in vitro to cultures initially established in the presence of 5 ng/ml NGF substantially increased the subsequent expression of neurofilament protein, this response being both independent of and not potentiated by NGF. The results in the present system suggest that GM1 cannot initiate a programme of neurite regeneration; however, GM1 can enhance this process with the response being secondary to the effect of NGF.

Animals↗
PubMed1984

The effect of nerve growth factor and its antibodies on neurofilament protein expression in primary cultures of sensory and spinal neurons.

An enzyme-linked immunoadsorbent assay has been used to quantify the binding of an antineurofilament monoclonal antibody, RT97, to primary cultures of embryonic chick dorsal root ganglion and spinal cord tissue. In the case of dorsal root ganglion cells a dose-dependent relationship between nerve growth factor (NGF) concentration and the level of RT97 binding was observed. This response could be antagonised by an anti-serum directed against NGF. In contrast, neither NGF nor the antiserum against NGF influenced the binding of RT97 in primary cultures initiated from chick spinal cord.

Animals↗
PubMed1984

Quantitative evaluation of neurite outgrowth in cultures of human foetal brain and dorsal root ganglion cells using an enzyme-linked immunoadsorbent assay for human neurofilament protein.

An enzyme-linked immunoadsorbent assay has been developed to evaluate comparative levels of neurofilament protein in developing primary cultures of human foetal dorsal root ganglion and brain tissue. The quantitative parameters of the assay, relating linearity of response with varying levels of neurofilament protein, were verified by comparing the relative binding of human species-specific (BF10) and cross-species-reactive (RT97) monoclonal antibodies to mixtures of human and baboon spinal cord homogenates that had been passively adsorbed onto microtitre wells. In human neural cultures, the localisation of neurofilament protein to growing neurites was determined by indirect immunofluorescence staining with anti-neurofilament antibodies and, using the immunoadsorbent assay, a time-dependent increase in the level of neurofilament protein was detected that correlated with the morphological time course of neurite development. In the case of dorsal root ganglion cells over 6 days in vitro, a seven- to ninefold greater increase in neurofilament protein levels was observed in cultures treated with nerve growth factor when compared with control unstimulated preparations. The quantitative responsiveness of dorsal root ganglion neurones to nerve growth factor detected by the neurofilament assay indicates its potential usefulness in the identification and analysis of neurotrophic and neurotoxic factors or cellular interactions operating in vitro.

Antibodies, Monoclonal↗
PubMed1984

Changes in miniature end-plate potentials after brief nervous stimulation at the frog neuromuscular junction.

The amplitude of miniature end-plate potentials (m.e.p.p.s), recorded at the frog neuromuscular junction in a normal ionic environment and in absence of drugs, was examined following 10-450 nerve impulses using conventional electrophysiological techniques and on-line computational analysis. In both contracting preparations and non-contracting preparations pre-treated with glycerol, 100 or more nerve impulses resulted in a maximal fall in mean amplitude of about 20% with recovery apparent over the next 10-20 min. In an altered ionic environment with a lowered Ca and raised Mg concentration, 450 nerve impulses did not produce a decrease in mean amplitude but a similar reduction was seen following a larger number of impulses. The reduction in amplitude was estimated to follow the release of the order of 5000-10000 quanta at end-plates in a normal ionic environment and on average 17000 quanta in the presence of a lowered Ca and raised Mg concentration. Changes in the mean size of the spontaneous quantal response is considered to be a presynaptic event and to reflect the loss and slow recovery of larger packets of transmitter from a vesicular store that is readily released by nerve impulses.

Animals↗
PubMed1983

Identification of cell-surface antigens present exclusively on a sub-population of astrocytes in human foetal brain cultures.

We have examined two monoclonal antibodies (McAbs; coded MI/N1 and 308) raised to human neuroblastoma cells for cell-type-specific reactivity in cultures of human neural tissues and in frozen sections of intact primate spinal cord. In dual-label immunofluorescence assays using established cell-type antigenic markers as positive controls, the reactivity patterns obtained with both McAbs MI/N1 and 308 were consistent with the detection of astrocyte-specific cell-surface antigens. No reactivity of the antibodies with other human neural cell-types, or with human muscle cells was detected. In cultures of human foetal brain a sub-population of astrocytic cells remained unlabeled by antibodies MI/N1 and 308. The significance of the latter observation has not yet been defined but may represent a developmental or functional division within the astrocytic cell lineage.

Antibodies, Monoclonal↗
PubMed1982

Survival of autotransfused red blood cells recovered from the surgical field during cardiovascular operations.

The survival of autologous red blood cells (RBCs) collected during operation from the surgical field and processed immediately by the Haemonetics Cell Saver was compared to the survival of autologous nonprocessed RBCs obtained by venipuncture in nine patients undergoing reconstructive vascular operations and four patients undergoing coronary artery bypass. A double isotope technique (Cr-51 and In-111) was used to determine the survival of the different cell populations. Seven patients undergoing coronary artery bypass served as controls to characterize the isotopes by labeling the same population of RBCs with each radionuclide. Comparison of the data in all groups failed to show any significant difference in either the immediate or long-term survival between autotransfused (Cell Saver--processed) blood and nonprocessed RBCs. This study indicates that shed blood collected and processed at operation with the Haemonetics Cell Saver can be autotransfused and that the in vivo survival of these cells is not significantly different from the survival of nonprocessed blood.

Blood Transfusion, Autologous↗
PubMed1981

Melatonin prevents decrease in plasma PRL and LH levels in male hamsters exposed to a short photoperiod.

Treatment of male golden hamsters with melatonin injections can cause a decrease in plasma gonadotropin and Prl levels and induce testicular regression. However, administration of melatonin via subcutaneously implanted Silastic capsules can prevent short photoperiod from causing the testes to regress. In order to explain this effect of melatonin capsules, we examined plasma Prl, LH and FSH levels in pinealectomized and sham-operated hamsters in which empty or melatonin-filled Silastic capsules had been implanted. After implantation, the hamsters were transferred to a short photoperiod (5 h L:19 h D) for 9 weeks. Both pinealectomy and melatonin completely prevented the decline in plasma Prl and LH levels and in the weight of the testes and the seminal vesicles. Moreover, testicular weight and plasma Prl and LH levels were higher in pinealectomized animals given melatonin capsules than in pinealectomized animals given empty capsules. In order to obtain some indication whether melatonin may affect testicular function directly, we have examined the influenced of melatonin on the production of testosterone by hamster testes in response to hCG in vitro. Addition of 0.2, 10 or 500 ng of melatonin per ml of incubation medium had no effect on testosterone production in this system. It is concluded that melatonin capsules prevent regression of the male reproductive system in short photoperiod, most likely by preventing the decline in plasma Prl and LH levels and that these effects of melatonin are not mediated through or dependent on the pineal.

Animals↗
PubMed1979

Reliability and reproducibility of interpretation of 99mtechnetium pyrophosphate myocardial scintigrams.

The interpretations of 156 99mtechnetium pyrophosphate myocardial scintigrams by four observers were analyzed in order to determine the reliability and reproducibility of the subjective process of reading scintigrams. The scintigrams were scored on an integral scale from 0 to 4, depending upon the degree of myocardial radionuclide accumulation, and the site and nature of uptake were specified. Exact agreement upon score was generally poor but approximate concurrence of interpretation was good (90.4 and 92.5% inter- and intra-observer agreement, respectively). There was somewhat less agreement on scintigrams with the higher scores of 3 and 4 (83.3 and 78.0%, respectively). A high level of concurrence upon the differentiation between diffuse and localized uptake, and upon the site of uptake, was found. We conclude that only approximate rather than exact agreement of individual readers' interpretations can be expected in this subjective technique, that scintigrams with higher degrees of radionuclide accumulation produce slightly greater observer disagreement, and that variability of interpretation could account for some of the diagnostic inaccuracy of 99mtechnetium pyrophosphate myocardial scintigraphy.

Angina Pectoris↗
PubMed1979

Gated cardiac scanning: canine studies.

Retrospective electrocardiograph gating of data from a rotating detector fan beam computed tomography system was employed to produce end systolic and end diastolic images of the beating heart in a series of normal and experimentally infarcted canines. The gating window was typically less than 20% of the cardiac cycle, and the gated images showed superior spatial resolution compared with ungated images of the same cross section. Comparison of the scans of the normal and of the infarcted animals shows abnormal contrast enhancement of the myocardium in the region of the infarct, and the gating studies demonstrate dyskinetic behavior of the infarct zone.

Animals↗
PubMed1978

Cellular immune response in virus infections.

Two levels of specificity exist in the killing of virus infected target cells by immune effector T cells. One relates to the classic specificity for the virus, and the second involves the necessity for sharing expression of genes mapping in K and D but not I regions. Among the theories that could explain this is that of dual recognition with separate T-cell receptors detecting H-2 and viral antigen. Support for this possibility was provided by experimental influenza virus infection where evidence of specific recognition of viral products was obtained.

Animals↗
PubMed1977

Reproducibility of thallium-201 myocardial imaging.

Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect ofvarying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91%) were reproducible. Only 53% (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies.

Adult↗
PubMed1976

Pregnancy in patients after valve replacement.

This report is based on information obtained from a questionnaire sent to major cardiac centres in the United Kingdom. This produced details of 39 pregnancies in 34 patients after valve replacement. The 39 pregnancies gave rise to 30 healthy babies. The small size of the series probably reflects both the increasing rarity of young women with rheumatic heart disease in this country and the cautious attitude of their cardiologists. This makes it likely that these women represented the best end of the spectrum of cardiac function after valve replacement. Twenty-four pregnancies in 20 women who were not given anticoagulants producted 23 healthy babies and 1 spontaneous abortion. This group comprised 6 patients with free aortic homografts, 1 patient with a fascia lata mitral valve, 1 with a Beall tricuspid prosthesis, 1 with a combined mitral homograft and Starr Edwards aortic prosthesis, and 1 with mitral and aortic frame-mounted fascia lata valves. There were no maternal deaths or thromboembolic complications in this group which included 5 patients who were in atrial fibrillation. Fifteen pregnancies in 14 women who received anticoagulants gave rise to 7 healthy babies. The fetal losses were one stillbirth, one intrauterine death at 34 weeks, and 3 spontaneous abortions; one surviving child has hydrocephalus as a result of blood clot and there were 2 maternal deaths. This group included 13 patients with Starr Edwards valves, 11 mitral and 2 aortic. A patient with a Hammersmith mitral valve was the only one to have been treated with heparin and her valve thrombosed. One patient with a mounted mitral homograft had a cerebral embolus. Nine of these patients were in atrial fibrillation. In 3 additional patients the valve replacement was carried out during pregnancy. Two of the patients survived operation. In one of these who was treated with warfarin the pregnancy well, but there is an increased fetal wastage in patients pregnancy gave rise to a congenitally malformed baby who died in the neonatal period. The baby born to the mother who did not receive anticoagulants has a hare-lip and talipes. Women with artificial valves can tolerate the haemodynamic load of pregnancy well, but there is an increased fetal wastage in patients taking oral anticoagulants. This is probably largely attributable to fetal haemorrhage but there is also a risk of malformation caused by a teratogenic effect of warfarin. Experience gained in non-pregnant patients suggests that withholding anticoagulatns in pregnant patients with prosthetic valves would usually be undersirable but warfarin should be avoided. The advantages of biological valves were apparent in this series.

Abnormalities, Drug-Induced↗