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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1993

Differential localization of endothelin ETA and ETB binding sites in human placenta.

1. The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands. 2. Specific, high density [125I]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 3. [125I]-ET-1 binding sites exhibited a rank order of inhibition by unlabelled peptide sequences (ET-1 > ET-3 > [Ala3,11,18Nle7]-ET-1 > BQ123 > or = sarafotoxin 6c). However, in contrast to the monophasic inhibition curve of ET-1, the other sequences produced a significantly better fit to a two component inhibition curve suggesting the presence of a heterogeneous population of ET binding sites. 4. ETA and ETB receptors were distinguished by competitive inhibition of [125]-ET-1 binding with increasing concentrations of unlabelled ET-3, [Ala3,11,18Nle7]-ET-1, sarafotoxin 6c and BQ123 and by incubating sections with the ETB agonist, [125I]-BQ3020. ET receptor subtypes exhibited a differential distribution in the placenta. ETA type binding sites predominated (approximately 80% of the total) on veins and arteries in the chorionic plate. Veins in stem villi, blood vessels in distal regions of the villous tree and decidual cells displayed a high density (approximately 60-70% of the total) of the ETB receptor subtype. 5. No difference was detected in either the relative density of [125I]-ET-1 binding sites or the proportion of ETA to ETB sites in placentae from pregnancies complicated by pre-eclampsia compared with normal term controls.6. ET may have a local autocrine or paracrine role in the placenta, acting via specific receptors to influence foetoplacental blood flow and other aspects of placental function.

Adult↗
PubMed1993

Intractable chest pain in cardiomyopathy: treatment by a novel technique of cardiac cryodenervation with quantitative immunohistochemical assessment of success.

A novel method of cardiac denervation by cryoablation has been developed experimentally. The technique uses liquid nitrogen delivered under pressure to ablate the principal sources of cardiac innervation--namely, the adventitia surrounding the aorta, pulmonary arteries, and veins. The technique has been verified experimentally both in vivo by physiological means and in vitro by quantitative immunohistochemistry and the measurement of myocardial noradrenaline concentrations. A 35 year old woman presented with intractable precordial pain, normal epicardial coronary arteries, and hypertrophic cardiomyopathy. Her symptoms were refractory to maximal medical treatment and she was thought to be unsuitable for either conventional myocardial revascularisation, autotransplantation, or allografting with the concomitant risk of transplant coronary artery disease. She therefore underwent cardiac denervation by the method developed in the laboratory. There was quantitative immunohistochemical evidence of extrinsic cardiac denervation associated with a considerable improvement in her symptoms. This improvement persisted during a follow up period of over 16 months.

Adult↗
PubMed1993

Development of the peptidergic innervation of human heart.

The aim of the present investigation was to study the developing peptidergic innervation of the human fetal heart of 7-24 wk gestational age. An immunohistochemical approach was adopted and the total innervation visualised with antisera to general neuronal and Schwann cell markers, while the onset and development of specific neuropeptide-containing subpopulations were investigated using antisera to neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP). Cardiac ganglia and nerves were demonstrated from 7 wk of gestation whereas peptide-immunoreactive nerves were not observed until the 10th week of gestation. NPY-immunoreactive nerve fibres constituted the major subpopulation of peptide-containing nerves identified in the fetal heart, exhibiting a descending atrial to ventricular density gradient, and were first identified during the 10th wk of gestation. Somatostatin- and VIP-immunoreactive nerves appeared at 10-12 wk of gestation and were mainly distributed in the atria. Somatostatin immunoreactivity was localised to cell bodies in cardiac ganglia, as well as to nerve fibres, indicating an intrinsic origin for this nerve subpopulation. Conversely, the other peptide-containing nerves appear to be of extrinsic origin, including those immunoreactive for VIP. Intracardiac neurons exhibit a transient expression of tyrosine hydroxylase immunoreactivity. Putative sympathetic nerve fibres, displaying tyrosine hydroxylase and NPY immunoreactivity, were demonstrated before the adrenergic innervation has previously been shown to be present by formaldehyde-induced fluorescence staining of catecholamines. The onset of the CGRP- and SP-immunoreactive innervation, at 18-24 wk of gestation, followed the appearance of other peptide-containing nerves, suggesting that the sensory, afferent innervation occurs later than the autonomic. The differential appearance and distribution of peptide-containing nerve subpopulations indicate that there is a chronological order to the development of the autonomic and sensory components of human cardiac innervation.

Calcitonin Gene-Related Peptide↗
PubMed1992

Endocardial localization and characterization of natriuretic peptide binding sites in human fetal and adult heart.

Specific, high affinity binding sites for 125I-human-alpha-atrial natriuretic peptide-(1-28)) (125I-hANP-(1-28)) were identified in human fetal and adult heart and the binding characterized using quantitative in vitro autoradiography. Binding sites were localized to atrial and ventricular endocardium, aorta, pulmonary arteries and epicardial mesothelium. Kinetic studies indicated a Kd value of 32 pM for ventricular endocardial 125I-hANP-(1-28) binding. The binding was completely inhibited by an excess (1 microM) of unlabelled hANP-(1-28), human brain natriuretic peptide-(1-32) (hBNP-(1-32)) and by the 'clearance receptor' specific ring-deleted analogue, C-ANP-(4-23). Competitive inhibition studies indicated a relative inhibitory potency for hBNP-(1-32) and C-ANP-(4-23) of 6% and 3% respectively. The data suggest that a distinct natriuretic peptide receptor subtype is expressed in the endocardium and in addition to a possible clearance function, may represent a site for feedback regulation and peptide interaction.

Analysis of Variance↗
PubMed1992

Biomechanical analysis of a step-cut technique for flexor tendon repair.

We compared the strength of a new step-cut technique for flexor tendon repair with that of the widely used Kessler-Tajima technique, giving special attention to the relative contributions of the core and epitendinous sutures. 36 flexor digitorum profundus tendons from human cadavers were used. Corresponding digits from the same donor were paired, and the two tendons of each pair were placed in the Kessler-Tajima and step-cut groups, respectively. Each group had three subcategories of repair: (1) core repair alone; (2) epitendinous repair alone; and (3) full repair. In the Kessler-Tajima repair, the core stitch contributed more to ultimate tensile strength, while the epitendinous stitch contributed more to gap formation resistance. In the step-cut repair, however, the epitendinous stitch contributed more to both measures of strength. The full step-cut repair was 65% stronger in resisting gap formation and had 84% more ultimate tensile strength than the full Kessler-Tajima repair. We attribute the greater strength of the step-cut repair to the additional number of epitendinous loops, which lie perpendicular to the long axis of the tendon.

Cadaver↗
PubMed1992

Induction of c-fos but not c-myc in S-91 cells by melanization signals.

Synthesis of the pigment melanin is a complex differentiated function performed by pigment cells in response to a variety of stimuli. The possible roles of the proto-oncogenes c-fos and c-myc in the control of pigmentation were studied using subconfluent, actively proliferating Cloudman S-91 murine melanoma cells stimulated to synthesize melanin by melanocyte stimulating hormone (MSH) or forskolin. Stimulation caused a significant increase in melanin synthesis when compared to control cells, but had no effect on cell growth. Northern analysis of total cellular RNA demonstrated rapid, transient induction of c-fos mRNA as early as 30 min after stimulation with MSH or forskolin. In contrast, there was no effect on the high constitutive expression of c-myc in these actively proliferating cells. These data strongly suggest that the induction of c-fos mRNA is an early genetic event in stimulation of melanin synthesis and thus this proto-oncogene may play a major role in the regulation of this differentiated function, as reported for other forms of cellular differentiation. In contrast, c-myc expression is unaffected and instead correlated with cellular proliferative capacity. These results are consistent with the hypothesis that the down-regulation of c-myc frequently observed during cell differentiation is not a necessary event, but rather reflects an associated decrease in cell growth rate. The S-91 melanoma system appears to provide a convenient model for study of the regulation for a single, well defined differentiated function that is independent of growth rate.

Animals↗
PubMed1992

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Animals↗
PubMed1992

Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study.

To determine whether pulsatile hypothermic perfusion with University of Wisconsin preservation solution is superior to topical cooling as a method for the preservation of amputated limbs, six pairs of amputated canine limbs were preserved for twelve to fifteen hours. One limb of each pair was subjected to topical cooling and the other, to pulsatile hypothermic perfusion with University of Wisconsin solution. The bioenergetic status of the limbs was monitored by 31phosphorus magnetic-resonance spectroscopy, and histological evaluation was performed to assess ischemic changes in the preserved tissue. The pH and tissue levels of adenosine triphosphate declined three times more slowly in the limbs that were preserved by pulsatile hypothermic perfusion than in the topically cooled limbs. Consistent with these findings, the perfused limbs also had less histological evidence of ischemic injury. The data from this in vitro study show that pulsatile hypothermic perfusion with University of Wisconsin solution, in combination with an optimum degree of topical cooling, is superior to topical cooling alone as a method of preserving the bioenergetic status of amputated limbs.

Adenosine↗
PubMed1992

Endometrial adenocarcinoma without prior hormone replacement in a diabetic patient with gonadal dysgenesis.

Patients with dysgenetic gonads and Turner syndrome are unlikely to develop endometrial carcinoma unless they have received unopposed estrogen replacement therapy. This case describes a 54-year-old woman with Turner syndrome and primary amenorrhea who developed adenocarcinoma of the endometrium without having received hormone replacement. Vaginal bleeding, a pelvic mass, and sepsis were the presenting symptoms. The patient also had diabetes mellitus and hypothyroidism. Polyglandular endocrine patterns are known to occur with a high frequency in these patients. The woman's chromosome studies revealed a modified 46,X,i(Xq) (isochromosome X). This is the first report of an isochromosome X patient to develop endometrial cancer without receiving estrogen replacement. The etiology of this rare case may be an increased propensity for patients with X-chromosome deletions to develop neoplasms in general, or extragonadal estrogen production.

Adenocarcinoma↗
PubMed1992

Fetal fracture healing in a lamb model.

A large animal model to assess fetal fracture repair and the ability to close excisional bony defects is presented. Incisional and excisional ulnar fractures were made in 14 midgestation fetal lambs, harvested at serial time points, and subjected to high-resolution low-kilovolt magnification radiographs, magnetic resonance imaging scans, and histologic analysis. Fetal fracture healing was characterized by early closure of excisional defects and rapid fracture healing with minimal or no soft-tissue inflammation or callus formation. Magnetic resonance imaging scans of the fractures revealed a characteristic pattern compatible with the histologic findings, namely, minimal inflammation in soft tissue adjacent to the fracture site. Histologic and magnification radiographic findings indicated that complete bony repair occurred within 21 days in incisional defects and within 40 days in excisional defects. In both cases, healed fetal bone resembled normal bone matrix. Excisional defects, including periosteum, of greater than three times the width of the bony cortex closed rapidly with virtually normal-appearing bony matrix and with minimal or no callus formation.

Animals↗
PubMed1991

Demonstration that bone mass is greater in black than in white children.

Osteoporosis and hip fractures are less common and bone mass is greater in black than in white women. To determine if bone mass is greater in black than in white children, bone mineral density (BMD) of the midradius by single-photon absorptiometry and BMD of the lumbar spine (L1-L4), trochanter, and femoral neck by dual-photon absorptiometry were measured in 20 black boys, 18 black girls, 33 white boys, and 35 white girls between the ages of 7 and 12 years. Mean age (10.4 +/- 0.3 versus 10.2 +/- 0.2 years) and body weight (39 +/- 2 versus 38 +/- 2 kg) in the blacks and whites, respectively, were not different in the two groups, and the ages and weights of the boys and girls were not different from each other. BMD were significantly greater in black than in white children at each site, in the black than in white boys at the trochanter and femoral neck, and in the black than in white girls at each site. In both races, BMD varied directly with age and body weight. Multivariate analysis showed that BMD were greater at the midradius, lumbar spine, trochanter, and femoral neck in the black than in the white children, that BMD of the lumbar spine was greater in the girls than in the boys, and that BMD of the trochanter and femoral neck were greater in the boys than in the girls. There were significant partial correlations between race and BMD and between BMD and body weight at each site, between sex and BMD at the lumbar spine, trochanter, and femoral neck, and between age and BMD at the midradius, trochanter, and femoral neck. Race, sex, age, and body weight together accounted for 49-66% of the variation in bone mass. Thus, BMD of the midradius, spine, and hip are greater in black than in white children, body weight and age are important determinants of bone mass, and some sex differences in bone mass are present at this age.

Absorptiometry, Photon↗
PubMed1991

Re-use of the recipient vessels of a microvascular transplant.

Three cases are described in which a second microvascular free flap, transplanted after a delay of several months, was provided perfusion by re-using the recipient vessels of the first flap in end-to-end fashion. In each patient healing of the second flap was uneventful, and both transplants continue to survive. Prior to harvesting the second transplant, a careful intraoperative examination was performed in which the vascularity of the original transplant was assessed. In each case, recipient vessel re-use represented the least risky of several options. The results of the present series suggest that vascularization from the transplant bed or surrounding tissues proceeds despite the fact that, initially, the only source of blood for the free flap flows through a single axial vessel. This single vessel can therefore be divided without loss of the transplant as long as the transplant bed has already provided vascularization to the flap. In our opinion, the timing of the second procedure and the quality of the transplant bed are the key factors in the survival of the transplants.

Adolescent↗