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Biomedical subjects

A Hayes

Publications and source records attributed to A Hayes.

At least 19 recordsLinked to original sources

Analysis of soluble human and mouse interferon-gamma receptors expressed in eukaryotic cells.

The extracellular domains of the human and mouse interferon-gamma receptors were produced in insect Spodoptera frugiperda cells infected with recombinant baculoviruses and in mammalian Chinese-hamster-ovary cells. The receptors expressed in both systems are secreted into the culture medium. Their signal peptides are cleaved off and the proteins show heterogeneity in glycosylation which, however, does not affect the capacity to bind interferon gamma or specific antibodies. The soluble mouse receptors exhibit binding capacities similar to those of cell-surface-anchored receptors, whereas the human receptors exhibit a lower binding capacity. All soluble receptors inhibit the binding of interferon gamma to cellular receptors and neutralize the antiviral activity exerted by interferon gamma. These receptors could therefore be useful for structure/function analyses and in vivo studies.

Animals

Determinants of hemodynamic results of balloon dilation of aortic recoarctation.

Between October 1982 and May 1990, balloon dilation of aortic recoarctation was attempted in 27 patients. In 1 case dilation was not performed owing to suspected aortic perforation. The remaining 26 patients had 30 procedures. The age at the first dilation ranged between 2.6 months and 18.3 years. After dilation, systolic gradient decreased from 49 +/- 17 mm Hg to 20 +/- 17 mm Hg (p less than 0.001). A reduction of gradient to less than or equal to 20 mm Hg occurred after the first dilation in 17 of 26 (65%) patients. Residual gradients between 25 and 80 mm Hg were present in the remaining 9 patients. During follow-up of 2 months to 6.7 years, 5 of 17 patients with a good initial result developed further recoarctation (2 had successful redilation, 2 had reoperation, and 1 is awaiting repeat dilation). Of 9 patients with gradients greater than 20 mm Hg after the first dilation, 1 had successful redilation and 3 had reoperation. The remaining 5 patients are being managed conservatively. 2 patients developed aneurysms after dilation (1 immediately and the other at 2 months). In all, 15 patients (58%) had a good, and 11 (42%) a poor late hemodynamic result. Aortic diameters at different levels of the aortic arch and at the reconstructed isthmus (normalized to the aorta at the level of the diaphragm) were significantly higher in the group with a good late result than in that with a poor one. Balloon/aortic diameter ratio at diaphragm level also had a significant influence on the late results.

Adolescent

Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa.

We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration.

Animals

Morphological evidence for biological control of urate crystal formation in vivo and in vitro.

Urate crystal formation, and subsequent gout, occurs in only a minority of hyperuricaemic subjects indicating that factors other than hyperuricaemia are involved. Biological substances (especially proteins) alter crystal growth in vitro independently of uric acid concentration. Physiological crystal formation, known to be under biological control, is characterised morphologically by uniformity of size and constraint of crystal shape. To determine whether pathological urate crystal formation is influenced by the surrounding biological milieu we examined, using scanning electron microscopy, the morphology of urate crystals formed either in vivo or in vitro. We found morphological evidence of biological control of in vivo urate crystal formation and demonstrated that those characteristics could be induced in vitro by the addition of serum, synovial fluid and certain serum proteins to the growth medium during crystal formation. Urate crystal formation is dependent, not only on the degree of hyperuricaemia, but also on the surrounding biological milieu.

Blood Proteins

Automaticity and preattentive processing.

The characteristics of automatized performance resemble those of preattentive processing in some respects. In the context of visual search tasks, these include spatially parallel processing, involuntary calling of attention, learning without awareness, and time-sharing with other tasks. However, this article reports some evidence suggesting that extended practice produces its effects through different mechanisms from those that underlie preattentive processing. The dramatic changes in search rate seem to depend not on the formation of new preattentive detectors for the task-relevant stimuli, nor on learned abstracted procedures for responding quickly and efficiently, but rather on changes that are very specific both to the particular stimuli and to the particular task used in practice. We suggest that the improved performance may depend on the accumulation of separate memory traces for each individual experience of a display (see Logan, 1988), and we show that the traces differ for conjunction search in which stimuli must be individuated and for feature search where a global response to the display is sufficient.

Attention

Cytoskeletal specializations at the rod photoreceptor distal tip.

We have examined microtubules and microtubule-like elements within the toad rod photoreceptor outer segment in order to define regional specializations of the photoreceptor cytoskeleton. "Ciliary" microtubules were localized within the rod outer segment (ROS) by using thin section electron microscopy, immunofluorescence, and rapid-freeze deep-etch microscopy. All three methods showed that ciliary microtubules stop short of the extreme ROS distal tip, although abundant microtubule-like structures distinct from the ciliary microtubules were found within the distal 10-15 microns of the ROS tip. These heretofore undescribed "distal ROS tubules" are clustered at the clefts or incisures of the disk membrane stack and resemble microtubules in overall size and shape, although they are not closely related antigenically to tubulin. The distal ROS tubules are more abundant in green rods than red rods and vary in number during the daily light/dark cycle. Quantitation of these tubules at two time points during the light/dark cycle suggests that there are three- to fourfold more tubules in the ROS tip one hour after light onset than one hour before light onset. Retinas prevented from normal disk membrane shedding by separation of the retina from the adjacent pigment epithelium, failed to develop increased numbers of tubules after light onset. This suggests that the newly described distal ROS tubules may modulate or be modulated by light-induced interactions between the photoreceptors and pigment epithelium, such as those that occur during the disk shedding phase of membrane turnover.

Animals

Double-outlet right ventricle: morphologic demonstration using nuclear magnetic resonance imaging.

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination. Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were less than 90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact. In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortem findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy. In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management.

Angiography

A 52 kD cytoskeletal protein from retinal rod photoreceptors is related to erythrocyte dematin.

A novel cytoskeletal antigen, RET52, has been identified in the mouse retina. This 52 kD polypeptide is antigenically related to dematin (band 4.9), an actin-bundling phosphoprotein component of the erythrocyte membrane skeleton. Like dematin, RET52 is also a substrate for cAMP-dependent protein kinase. Within the retina, RET52 is primarily concentrated in two regions-the rod inner segment and the outer synaptic layers-although the developmental expression of RET52 differs in these areas. RET52 is present at birth in the inner segment, but appears about the time of initial synapse formation (postnatal day 4-6) in the outer plexiform layer. No differences in RET52 expression have been detected in early-stage mouse retinas with the retinal degeneration (rd) phenotype. RET52 localization, developmental expression, homologies to dematin, and in vitro phosphorylation pattern suggest a possible role for cytoskeleton-associated proteins in the initiation or control of disk membrane assembly and/or synapse formation in the rod photoreceptor.

Animals

Magnetic resonance imaging of the great arteries in infants.

Sixty infants, aged 1-48 (median 8) weeks, with suspected congenital heart disease underwent a morphological evaluation of the great arteries using magnetic resonance imaging at 1.5 Tesla. Cross-sectional echocardiography was performed in all infants, angiography in 33 and surgery in 44. Multiple sections, 5 mm thick and gated to the patients' electrocardiogram were acquired in standard and oblique imaging planes. Ventriculo-arterial connexions were correctly identified in 54 infants (6 did not have intracardiac imaging performed) and an accurate description of the relationships of the great arteries was made in all. Magnetic resonance imaging clearly demonstrated normal and hypoplastic pulmonary arteries to the level of the first hilar branches and was better than echocardiography at confirming the presence or absence of central intrapericardial pulmonary arteries in 4 infants with pulmonary atresia. All parts of the thoracic aorta were accurately demonstrated and, in 23 infants with clinical suspicion of aortic coarctation, magnetic resonance images provided more information than echocardiography. Magnetic resonance imaging accurately demonstrates great arteries non-invasively supplementing echocardiographic and angiographic findings. In many cases, it replaces the need for invasive investigations.

Aorta, Thoracic

Morphological evaluation of atrioventricular septal defects by magnetic resonance imaging.

Twelve patients aged between 2 weeks and 22 months (median 6 weeks) with atrioventricular septal defects were examined with a 1.5 T, whole body, magnetic resonance imaging system. Ten patients had a common atrioventricular orifice (complete defect) while two patients had separate right and left valve orifices (partial defect). Associated cardiac malformations included the tetralogy of Fallot in two, isomerism of the right atrial appendages and pulmonary atresia in two, and right isomerism and double outlet right ventricle in one. All had previously been examined by cross sectional echocardiography. Eight subsequently had angiography and six underwent surgical correction. There was one operative death and three other deaths. Three of these patients underwent postmortem examinations. Small children and infants were scanned inside a 32 cm diameter head coil. Multiple electrocardiographically gated sections 5 mm thick, separated by 0.5 mm, were acquired using a spin echo sequence with echo time of 30 ms. A combination of standard and oblique imaging planes was used. Magnetic resonance imaging was more accurate than echocardiography in predicting the size of the ventricular component of the defect. It was also better than either echocardiography and angiography in identifying the presence of ventricular hypoplasia. All these findings were confirmed by surgical or postmortem examinations or both. Magnetic resonance imaging is capable of providing detailed morphological information in children with atrioventricular septal defects which is likely to be of value in their management.

Abnormalities, Multiple

Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Recognition of an in vivo immune response to human neuroblastoma modulation of antigen expression by retinoic acid.

Neuroblastoma is one of the most common solid tumors of childhood and is notable for its ability to spontaneously regress and, in some instances, to differentiate to less malignant ganglioneuromas. Since immune mechanisms may account for these phenomena, identification of in vivo immune responses to tumor cell surface antigens may be important to the progression of the disease. As determined by analysis on the fluorescence-activated cell sorter, sera from 10 of 18 neuroblastomas patients were found to contain antibodies to a cell surface antigen present on subpopulations of cells from human neuroblastoma cell lines maintained in vitro. Eight human neuroblastoma cell lines were examined and found to vary in reactivity with sera. Induction of differentiation of cell lines with retinoic acid (RA) in vitro resulted in most cell lines bearing higher percentages of positive cells but with a decreased mean cell fluorescence. Preliminary Western blot analysis of lysates of the human cell lines NMB/N7, SMS-KAN, and SK-N-MC showed two principal antigen bands on reducing gels. Comparison of sera from different individuals on lysates of cell lines showed reactivity principally with bands of 105-110 kD and 65-70 kD and an additional minor band of slightly lower molecular weight with the higher titer sera. The ability of different sera to recognize a common antigen pattern suggests that this represents an immunodominant cell surface antigen. Examination of reactivity of other cell lines in this system showed that positive sera reacted with all neuroblastoma lines examined, one neuroepithelioma (SK-N-MC), two melanoma lines (MeWo, G361), and one adrenal-derived adenocarcinoma (SW-13).

Antibody Formation

Frictional response of articular cartilage containing crystals.

Many joint diseases are associated with the deposition of crystals in articular cartilage. Three main types are commonly found: calcium pyrophosphate, calcium hydroxyapatite and monosodium urate. The effects of these articular crystals on the frictional properties and the surface condition of the articular cartilage were studied. A total of 43 cartilage specimens cut from 19 post-mortem knee joints have been tested in purpose-designed apparatus. The results show that a high friction coefficient and a high level of crystal deposition tend to occur with a worsening of the surface quality of the articular cartilage.

Biocompatible Materials

Serum levels of beta-carotene, vitamin A, and zinc in male lung cancer cases and controls.

The mean serum levels of beta-carotene and vitamin A in a multivariate analysis of data from 64 histologically confirmed male lung cancer cases were statistically significantly lower than those from 63 randomly selected male hospital controls, who were admitted for small surgical operations (p values for both beta-carotene and vitamin A less than 0.001). The mean serum levels of zinc were not statistically significantly different between cases and controls (p = 0.10). The levels of beta-carotene, vitamin A, or zinc were not statistically significantly influenced by either the extent of the cancer (p = 0.45) or the cancer cell type (p = 0.06). The possible biological significance of these findings is discussed briefly.

Adenocarcinoma

Dietary and alcohol intake, smoking pattern, occupational risk, and family history in lung cancer patients: results of a case-control study in males.

In a case-control study of 71 consecutive new male cases of lung cancer and 71 male hospital control patients, previous dietary and alcohol intake, smoking pattern, occupation, dust exposure, and family history of lung cancer were investigated. The cases and controls were similar in age, country of origin, area of residence, and marital status. Using a frequency-based assessment of previous dietary intake, broad food groups were similar for cases and controls. Cases had a significantly lower intake of fish than controls did (odds ratio = 0.5, confidence interval = 0.2-1.0, p = 0.05). A protective effect for fish consumption in lung cancer has not been previously reported. The dietary intake of foods containing retinol and beta-carotene and the intake of alcohol were not significantly different between cases and controls. For cases, smoking duration was longer and the time since cessation for exsmokers was shorter, cigarette pack years were longer, and the number of cigarettes smoked per day was greater. The factors of occupation, dust exposure, and family history of cancer (including lung cancer) were similarly distributed between cases and controls.

Adenocarcinoma

Superior QRS axis in ventricular septal defect.

The relation between the superior orientation of the QRS axis and the anatomical site of the defect in the ventricular septum in patients with a ventricular septal defect was studied. Of 1031 patients with a ventricular septal defect, 64 (6.2%) had a superior axis on their electrocardiogram. In 59% of these patients the defect was in the inlet portion of the ventricular septum or affected this area. None of the cases was classified as an isolated ventricular septal defect of the persistent atrioventricular canal type. While there is an association between a superior axis and perimembranous inlet ventricular septal defect, a superior QRS axis does not characterise a ventricular septal defect as being of the atrioventricular canal type.

Echocardiography

Neonatal screening and an intensive management programme for galactosaemia: early evidence of benefits.

A prospective study of children with galactosaemia is being undertaken at the Metabolic Clinic, Royal Children's Hospital, Brisbane. The purpose of the study is to collect biochemical, clinical, dietary, developmental and speech and language data. This paper describes the operation of the multiprofessional management programme and reports results for two groups of children: those who were diagnosed before the introduction of neonatal screening in 1982 (the prescreening group) and those who were identified by screening. The eight children in the prescreening group have shown intellectual development in the low-average to moderately-handicapped range. Most of them have speech and language difficulties. The screening group, all of whom are still in infancy or early childhood, appears to be developing normally, with the exception of one child who is showing problems with speech and language. The early results provide a basis for cautious optimism that neonatal screening and careful management will result in improved outcomes for children with galactosaemia.

Galactosemias