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Biomedical subjects

L Gordon

Publications and source records attributed to L Gordon.

At least 91 records · Page 5Linked to original sources
PubMed1994

A segment of the MHC class II beta chain plays a critical role in targeting class II molecules to the endocytic pathway.

The ability of MHC class II molecules to sort into the endocytic pathway has generally been attributed to the invariant chain glycoprotein. In this paper, we present evidence suggesting that lumenal sequences in the MHC class II molecule itself control the post-Golgi entry of class II into endosomes. Single amino acid changes have been introduced into a highly conserved region of the class II beta chain (amino acids 80-83). Mutant class II beta chain genes and wild-type alpha chain genes have been transfected into cells that lack both class II and invariant chain expression. Immunofluorescent staining of transfected cells indicates that single amino acid changes in this region of beta can positively or negatively modulate expression of class II in endocytic vesicles independently of invariant chain. Mutation at residue 80 leads to prominent localization in vesicular structures typical of late endocytic compartments, while a change at position 82 leads to arrest in the Golgi. These data argue in favor of the possibility that MHC class II molecules bear a sorting signal that allows access to MHC class II molecules into the endocytic pathway of antigen presenting cells.

Animals↗
PubMed1994

Scintigraphic diagnosis of peritoneo-pleural communication in the absence of ascites.

Pleural effusion in the presence of cirrhosis and ascites is well recognized. Peritoneal fluid is thought to enter the pleural cavity either because of overloaded lymphatics or a structural defect between the peritoneal and chest cavities. Pleural effusion rarely occurs in the absence of demonstrable ascites. This report describes the scintigraphic diagnosis of peritoneo-pleural communication in a patient with cryptogenic cirrhosis and pleural effusion without ascites.

Ascites↗
PubMed1994

Transport proteins and acute phase reactant proteins in children with sickle cell anemia.

Transport proteins, acute-phase reactant proteins (APRP), hematology, and anthropometry were studied in 34 sickle cell disease (SCD) children (20 boys, 14 girls) and 27 controls without growth deficits (13 boys, 14 girls) [corrected]. The age range was 1/2 to 16 1/2 years. Weight deficits (< 80%) by Waterlow's classification were observed in 41% of SCD boys and 25% of SCD girls, and height deficits (< 90%) were observed in 25% SCD boys and 25% girls. Mean white blood cell counts were significantly higher (P < .001) and hematocrit and hemoglobin (Hb) lower (P < .005) in SCD children than in controls. Although both groups had similar mean levels of albumin, transferrin, and APRP, SCD children had significantly lower mean levels of retinol-binding protein (RBP) (P < .001) and retinol-prealbumin (P < .001). Retinol-binding protein levels were abnormal in 18 (53%) SCD children and in only 23% controls (chi 2 = 14.06; P < 0.005); transferrin levels were abnormal in 20% of SCD children and in none of the controls. Children with SC and SF Hb phenotype had normal mean levels of RBP, whereas those with S beta thal and SS phenotype had levels below normal. Growth-retarded children by weight and height had reduced mean levels of RBP and prealbumin compared with growth-normal SCD children. The implication of primary protein-energy malnutrition on growth retardation in SCD children is under study.

Acute-Phase Proteins↗
PubMed1993

Expression of the human neuropeptide tyrosine Y1 receptor.

Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Y1 receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (approximately 2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Y1 receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions of NPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.

Adult↗
PubMed1993

Organization of the multiple polymorphic sites of the D19S11 locus within a 650-kb cosmid contig.

The D19S11 locus has been previously described as consisting of a complex set of six nonallelic polymorphic sites detected with a combination of four restriction enzymes and three probes that were subcloned from a single cosmid. These probes also hybridized to additional nonvariant fragments on Southern blots of human genomic DNA. In the course of establishing a contig map of human chromosome 19, a set of cosmids that were positive for at least one of the probes defining this locus was identified. These cosmids, along with additional cosmids, were assembled using a combination of strategies, including fluorescence in situ hybridization studies using G1 interphase nuclei and sperm pronuclei as chromatin targets, into a single overlapping set of cosmids that spans approximately 650 kb. Cosmids that are positive for the MEL gene probe are localized at the centromeric end of the spanning path, with some cosmids being positive for both the MEL gene probe and one of the D19S11 probes. The EcoRI fragments with homology to the various probes have been identified; some cosmids have homology to all three D19S11 probes. The positions for five of the six polymorphic sites were localized within a 40-kb region, with four sites within 15 kb.

Blotting, Southern↗
PubMed1993

Quantitative immunohistochemical assessment of bovine myocardial innervation before and after cryosurgical cardiac denervation.

OBJECTIVE: The aim was to determine the relative distribution and possible origins of peptide containing nerves in the bovine heart before and after functional extrinsic denervation established by cryosurgery. METHODS: A quantitative immunohistochemical technique was used. RESULTS: In the intact heart, myocardial nerve fibres and fascicles displaying immunoreactivity for the general neural marker protein gene product 9.5 had an atrial to ventricular gradient in density. The right atrium was the most densely innervated region and a major proportion of the total myocardial innervation, visualised by protein gene product 9.5 immunoreactive nerves, showed neuropeptide tyrosine (45%) and tyrosine hydroxylase (20%) immunofluorescence staining, while nerves immunoreactive for vasoactive intestinal polypeptide and calcitonin gene related peptide formed relatively minor subpopulations (representing less than 2% and 0.5%, respectively, of the total fluorescent myocardial innervation). Following cryoablation there was a significant reduction in the percentage fluorescent area of protein gene product 9.5 immunoreactive nerves throughout the heart, of greater than 90% of the control values. There were highly significant reductions in the percentage fluorescent area of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide, to 1.01, 0.92, and 0.05%, respectively, of the intact myocardial innervation. The distribution of vasoactive intestinal polypeptide immunoreactive nerves was more variable and displayed an equivocal response to cardiac cryoablation. CONCLUSIONS: The majority of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide are of extrinsic origin, while vasoactive intestinal polypeptide immunoreactive nerves may have intrinsic as well as extrinsic origins. The distribution and apparent origins of immunohistochemically defined nerves in the bovine heart are similar to those observed in the human heart which suggests that the calf may be an appropriate model for comparative studies.

Animals↗
PubMed1993

The diagnosis of brain death with Tc-99m HMPAO.

Evaluation of blood flow to the brain using various radiopharmaceuticals can be used to confirm brain death. Agents available for this purpose include Tc-99m HMPAO, Tc-99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m DTPA. The authors evaluated the use of Tc-99m HMPAO in 17 patients suspected of brain death using flow images and static images at several time intervals: immediately, between 30 and 60 minutes, and at 2 hours. These studies were compared to several studies performed with Tc-99m glucoheptonate and Tc-99m DTPA. The results of the Tc-99m HMPAO brain death studies correlated well with the patients' clinical conditions. Static images 1 to 2 hours after the injection of 5 to 30 mCi of Tc-99m HMPAO were satisfactory for an accurate interpretation; however, an immediate answer could as easily be supplied using flow images alone. Tc-99m HMPAO was found to be more easily interpreted and less dependent on imaging technique than Tc-99m glucoheptonate and Tc-99m DTPA, and it is the agent of choice for the evaluation of brain death.

Adolescent↗
PubMed1993

The serratus anterior free-muscle transplant for reconstruction of the injured hand: an analysis of the donor and recipient sites.

The present study evaluated donor-site function in eight patients for whom serratus anterior free-muscle transplantation was performed to treat a traumatic defect of the palm. The lowest two or three slips of the muscle were transferred from the uninjured side and covered with split-thickness skin grafts. After an average follow-up period of 50 months (range 13 to 84 months), function and appearance of the flaps were assessed, and shoulder strength on the donor side was objectively tested in six patients by using an isokinetic computerized robotic dynamometer. No patient noticed any change in upper extremity function following the procedure. Each of the three patients in whom three slips had been taken displayed mild scapular winging, but none complained of any related symptoms. Neither push strength nor abduction strength on the donor side was significantly different compared with that on the recipient side. The transplanted muscle provided excellent contour and durable cover in all eight hands with limited donor-site morbidity. For this reason, the serratus anterior transplant is our flap of choice for the treatment of large palmar defects.

Adult↗
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↗