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Biomedical subjects

G R Martin

Publications and source records attributed to G R Martin.

At least 163 records · Page 9Linked to original sources
PubMed1991

Effects of hydralazine on cardiac performance in infants receiving extracorporeal membrane oxygenation.

To determine the effects of afterload reduction on cardiac performance during partial cardiopulmonary bypass, we administered hydralazine to infants who were either normotensive (n = 11) or hypertensive (n = 12) 1 hour after extracorporeal membrane oxygenation (ECMO) was begun. Load-dependent and load-independent measures of cardiac performance and indexes of cerebral blood flow were measured. Infants in both groups had similar weight, heart rate, blood pressure, and inotropic support before ECMO. Shortening fraction was normal in both groups before ECMO (47 +/- 11% vs 49 +/- 10%; p greater than or equal to 0.05), decreased during ECMO (31 +/- 18% vs 39 +/- 12%; p greater than or equal to 0.05), and did not change after administration of hydralazine (31 +/- 12% vs 37 +/- 8%; p greater than or equal to 0.05). Cardiac output was normal in both groups before ECMO (176 +/- 71 vs 157 +/- 72 ml/kg per minute; p greater than or equal to 0.05), decreased during ECMO (120 +/- 80 vs 105 +/- 64 ml/kg per minute; p greater than or equal to 0.05), and did not change after hydralazine administration. Velocity of circumferential fiber shortening, an index of contractility (circumference per second), was normal in both groups before ECMO (1.96 +/- 0.57 vs 1.90 +/- 0.43 circ/sec; p greater than or equal to 0.05), decreased during ECMO (1.18 +/- 0.83 vs 1.56 +/- 0.58 circ/sec; p greater than or equal to 0.05), and did not change after hydralazine administration. The relationship between velocity of circumferential fiber shortening and wall stress was similar in both groups before ECMO, during ECMO, and after hydralazine administration. The cerebral blood flow resistance index was similar in both groups before ECMO (0.70 +/- 0.16 vs 0.70 +/- 0.20; p greater than or equal to 0.05), decreased during ECMO (0.45 +/- 0.13 vs 0.43 +/- 0.09; p greater than or equal to 0.05), and did not change after administration of hydralazine. We conclude that hydralazine does not improve cardiac performance during ECMO.

Blood Flow Velocity↗
PubMed1991

Epidermal growth factor (EGF) expression in the congenital polycystic mouse kidney.

The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease remain unknown, although abnormalities of cellular metabolism, basement membrane components, and growth factors have been suggested. In the present study, we examined a potential role for epidermal growth factor (EGF) in cyst formation in a mouse model. We measured growth factor activity and concentration in renal cyst fluid, urine, and serum obtained from mice with congenital polycystic kidney disease (cpk). In affected mice, both growth factor activity of urine and the urinary EGF concentration were much lower than unaffected littermate controls even when corrected for creatinine concentration. Although the growth factor activity was much lower in affected mice, there were significant differences in the regional distribution of EGF in animals with cysts. Both growth factor activity and EGF concentration were greater in cyst fluid when compared to urine. Growth factor activity in cysts was completely inhibited by anti-EGF antibody using BALB/MK epithelial keratinocytes as targets. The expression of EGF mRNA in kidneys from affected mice was markedly decreased when compared to littermate controls. These results suggest that decreased EGF production and local differences in EGF concentration may contribute to cyst formation.

Animals↗
PubMed1991

Effects of iron depletion and sub-inhibitory concentrations of antibodies on siderophore production by Staphylococcus aureus.

The effect of various sub-MICs of oxacillin and amikacin, alone or in combination, on siderophore production by Staphylococcus aureus growing under iron-depleted conditions was evaluated. Siderophore production varied greatly from strain to strain, ranging from 3.0 to 383.4 microM of Desferal equivalents. Siderophore production by some S. aureus strains was reduced significantly (P less than 0.001) under some sets of conditions. However, siderophore excretion in cultures with amikacin was sometimes equal to or greater than control cultures. Thus, at some sub-MICs, the bacteria tested were able to increase siderophore production under metabolic stress. This phenomenon may be a secondary effect of the antibiotics upon intermediary metabolism as a consequence of inhibition of peptidoglycan or protein synthesis. Alternatively the antibiotics may decrease the cellular association of siderophore molecules.

Amikacin↗
PubMed1991

Propagation and properties of Kaposi's sarcoma-derived cell lines obtained from patients with AIDS: similarity of cultured cells to smooth muscle cells.

Cells derived from Kaposi's sarcoma (KS) were propagated in vitro using conditions which resulted in elimination of contaminating fibroblasts and the emergence of homogeneous cell populations which morphologically resembled smooth muscle cells and had neoplastic characteristics. In long-term culture, they differentiated into large ribbon-like cells with longitudinal fibrillarity of their cytoplasm. These fibrils stained red by Masson trichrome staining, and were reactive with antibodies to desmin. Dense bodies typical of myoblasts were observed in some cells by electron microscopy. The cells did not form capillary structures like endothelial cells, they lacked Weible-Palade bodies, and did not express the blood-clotting Factor VIII-related antigen or receptors for the lectin Ulex europaeus agglutinin I. They did express four other antigens, however, in common with endothelial cells. The cells did not form tumors in athymic nude mice; however, they formed colonies in soft agar, manifested tumor-like growth on muscle organ cultures, and were invasive in an artificial basement membrane invasion assay. The results indicate that a component of KS is closely related to leiomyoblasts and and has neoplastic properties.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A comparative study of the prostanoid receptor profile of 9 alpha 11 beta-prostaglandin F2 and prostaglandin D2.

1. The aim of this study was to determine the receptor profile of 9 alpha 11 beta-prostaglandin F2 (PGF2) and compare it with that of its parent, prostaglandin D2 (PGD2). The experiments were designed to overcome the problems associated with the presence of multiple prostanoid receptor sub-types in most tissues; the lack of selective antagonists for each receptor means that conclusions regarding efficacy at FP and EP2 receptors must remain provisional. 2. At DP receptors in human platelets and rabbit jugular vein, PGD2 was a full agonist, p[A50] 7.02 +/- 0.09 and 6.60 +/- 0.12 respectively. 9 alpha 11 beta-PGF2 was approximately 30-60 fold less potent than PGD2. 3. 9 alpha 11 beta-PGF2 was a full agonist in the FP receptor containing preparation, cat iris sphincter (p [A50] 7.35 +/- 0.09) comparable in potency to PGD2 (p[A50] 7.15 +/- 0.19). Likewise the two prostanoids showed similar potency at the TP receptor in guinea-pig aorta (9 alpha 11 beta-PGF2 p[A50] 6.00 +/- 0.07; PGD2 6.24 +/- 0.08). 4. 9 alpha 11 beta-PGF2 and PGD2 had efficacy but low potency at EP1 receptors (guinea-pig oesophageal muscularis mucosa) and demonstrated 2000-3000 fold lower potency than PGE2 (p[A50] 8.35 +/- 0.09). Similarly, in the EP2 receptor-containing preparation, cat trachea, 9 alpha 11 beta-PGF2 was 3500 fold less potent and PGD2 700 fold less potent than PGE2 (p[A50] 8.06 +/- 0.26). 5. 9 alpha 11 beta-PGF2 and PGD2 (10 microM) were without affinity at the IP receptors on human platelets and had no agonist action in the EP3 receptor containing preparation, guinea-pig vas deferens. 6. 9 alpha 11 beta,-PGF2 is a major metabolite of PGD2 in vivo and this conversion clearly represents an inactivation step since 9 alpha 11 beta-PGF2 is of considerably lower potency than PGD2 at DP receptors. However, it is of similar potency to PGD2 at TP, FP, EP1 and EP2 receptors and it may, therefore, contribute to the biological effects which follow PGD2 administration or endogenous synthesis; its actions at these receptors are likely to be similar to those of PGD2 itself.

Animals↗
PubMed1991

Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals.

The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half-lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals.

Animals↗
PubMed1991

The eye of a procellariiform seabird, the Manx shearwater, Puffinus puffinus: visual fields and optical structure.

The Manx shearwater, Puffinus puffinus, is a pelagic sea bird which feeds from the surface of the sea and by shallow surface and plunge dives. Visits to breeding colonies are made at night. The mononuclear retinal field of the Manx shearwater eye is 148 degrees wide and is asymmetric with respect to the optic axis. The nasal and temporal hemi-fields equal 65 and 83 degrees, respectively. The binocular field is long and narrow, and the central placement of the bill suggests that vision is used to guide the bill position during foraging. A schematic model of the shearwater eye's optical system is presented, together with reanalysed data on the optical structure in the eye of the pigeon, Columba livia. The eyes of these two species are nearly identical in axial length and overall shape, but they are of quite different optical design. The shearwater eye has a shorter focal length and higher maximum image brightness, and the ratio of corneal:lens refractive power equals 0.4 and 1.6 in pigeon and shearwater eyes, respectively. In Manx shearwater eyes, the ratio of focal length:axial length and the ratio of lens refractive power:corneal refractive power may be correlated with a nocturnal life style. It is not clear whether the relatively low refractive power of the cornea is best regarded as a feature correlated with an amphibious life style or whether it is a consequence of adaptations for nocturnal activity.

Animals↗
PubMed1991

Novel area serving binocular vision in the retinae of procellariiform seabirds.

Procellariiforms are pelagic seabirds which fly close to the sea surface and feed either by taking items from the surface or by shallow diving. The retinal ganglion cells in five species (Manx shearwater, Puffinus puffinus, Kerguelen petrel, Pterodroma brevirostris, great shearwater, Puffinus gravis, broad-billed prion, Pachyptila vittata, and common diving petrel, Pelecanoides urinatrix) were examined by Nissl staining and also by silver staining in the case of the common diving petrel. In all five species, a well-defined region in the dorsotemporal retina, close to the ora, was identified. This region is characterized by the presence of ganglion cells which are both regularly arrayed and larger than those found in the rest of the retina. These cells also have a large dendritic field of sparsely branched dendrites with much dendritic overlap between cells, thick axons, and dendrites confined to the proximal inner plexiform layer. Morphologically, they appear similar to the alpha cells of the retina in cats. It is suggested that the region containing these cells should be regarded as a retinal area, and the name area giganto cellularis is proposed. In the Manx shearwater, it is found that this novel area projects visually into the binocular field below the bill. Unlike previously described areas in avian retinae, it seems that this novel area is not concerned with high spatial resolution. It may function in the detection of objects on the sea surface and/or be concerned with the detection of the actual sea surface as a bird flies low over it.

Animals↗
PubMed1991

mRNA localization studies suggest that murine FGF-5 plays a role in gastrulation.

During gastrulation in the mouse, the pluripotent embryonic ectoderm cells form the three primary germ layers, ectoderm, mesoderm and endoderm. Little is known about the mechanisms responsible for these processes, but evidence from previous studies in amphibians, as well as expression studies in mammals, suggest that signalling molecules of the Fibroblast Growth Factor (FGF) family may play a role in gastrulation. To determine whether this might be the case for FGF-5 in the mouse embryo, we carried out RNA in situ hybridization studies to determine when and where in the early postimplantation embryo the Fgf-5 gene is expressed. We chose to study this particular member of the FGF gene family because we had previously observed that its pattern of expression in cultures of teratocarcinoma cell aggregates is consistent with the proposal that Fgf-5 plays a role in gastrulation in vivo. The results reported here show that Fgf-5 expression increases dramatically in the pluripotent embryonic ectoderm just prior to gastrulation, is restricted to the cells forming the three primary germ layers during gastrulation, and is not detectable in any cells in the embryo once formation of the primary germ layers is virtually complete. Based on this provocative expression pattern and in light of what is known about the functions in vitro of other members of the FGF family, we hypothesize that in the mouse embryo Fgf-5 functions in an autocrine manner to stimulate the mobility of the cells that contribute to the embryonic germ layers or to render them competent to respond to other inductive or positional signals.

Animals↗
PubMed1991

Cardiac stun in infants undergoing extracorporeal membrane oxygenation.

Previous studies have shown that cardiac performance decreases in infants undergoing extracorporeal membrane oxygenation (ECMO). Some infants have an exaggerated decrease in cardiac performance during ECMO. This syndrome has been called cardiac stun. To better understand this phenomenon, we reviewed the records of infants with cardiac stun and compared them with infants who did not have the syndrome. Cardiac stun was detected in 12 of 240 infants (5.0%) undergoing ECMO. The diagnoses were congenital diaphragmatic hernia (7/12), meconium aspiration syndrome (3/12), respiratory distress syndrome (1/12), and persistent pulmonary hypertension of the newborn (1/12). The weight, gestational age, inotropic support, and time to start of ECMO were similar to infants without cardiac stun. Arterial oxygen tension was lower, carbon dioxide tension was higher, and pH was lower before ECMO in infants in whom cardiac stun developed (p less than or equal to 0.03). Cardiac arrests were more common, before ECMO, in infants in whom cardiac stun developed (6/12; p less than or equal to 0.01). Cardiac stun began at an average 2 1/2 hours after beginning ECMO (range 0.1 to 7 hours). Pulse pressure decreased from 20 mm Hg (range 10 to 45 mm Hg) before stun to 8 mm Hg (range 4 to 12 mm Hg) after stun. Heart rate did not change. Cardiac stun lasted for 33 hours (range 1 to 64 hours) on ECMO and recurred in three infants. Decreases in pump flow and increases in preload, afterload reduction, and inotropic agents did not improve cardiac performance. Survival was lower in the infants in whom cardiac stun developed (p less than or equal to 0.001). Only 5 of 12 infants (42%) survived ECMO when cardiac stun occurred. Our findings show that cardiac stun occurs infrequently during ECMO and is transient in most infants. Infants in whom cardiac stun develops appear to be more ill before ECMO and have a higher mortality after ECMO.

Aorta↗
PubMed1991

Effects of synthetic peptides and protease inhibitors on the interaction of a human ovarian cancer cell line (NIH:OVCAR-3) with a reconstituted basement membrane (Matrigel).

We have investigated the adhesive properties and invasiveness of cells of the human ovarian carcinoma line, NIH:OVCAR-3, in vitro. OVCAR-3 cells exhibited a similar rate of adhesion to all substrates tested including laminin, fibronectin, and collagens I and IV. The synthetic peptide YIGSR-NH2, which corresponds to an attachment site in laminin, inhibited the adhesion of the cells to laminin, but not to fibronectin. In contrast, a GRGDS-NH2 peptide blocked adhesion to fibronectin but not to laminin. OVCAR-3 cells invaded and formed branched colonies on Matrigel. Colony formation was retarded by both YIGSR-NH2 and GRGDS-NH2 peptides. Serine protease inhibitors and human recombinant TIMP, the tissue inhibitor of metalloproteases, inhibited ovarian tumor cell invasion while a synthetic collagenase IV inhibitor (SC-44463) had no effect. These studies suggest that metalloproteases other than collagenase IV may be important for the invasive activity of ovarian cancer cells. It is possible that synthetic peptides with antiadhesive cellular activity and certain antiproteases could be used to control the progressive colonization and invasion of peritoneal surfaces by malignant ovarian cancer cells.

Amides↗
PubMed1990

Analysis of the 5-HT receptor in rabbit saphenous vein exemplifies the problems of using exclusion criteria for receptor classification.

5-Hydroxytryptamine (5-HT) contracts ring preparations of rabbit saphenous vein via direct and indirect components, the latter being compatible with a "tyramine-like" action at sympathetic nerve terminals. Here an attempt was made to establish the identity of the receptor mediating contraction directly, in terms of the currently accepted proposals (Bradley et al. 1986). Results with agonists suggested 5-HT1-like receptor activation: methylsergide behaved as a partial agonist with microcolar affinity and 5-HT effects were mimicked by 5-carboxamidotryptamine (5-CT) and GR43175. The agonist potency order was 5-CT greater than 5-HT greater than methysergide greater than or equal to GR43175, the same as that reported at the 5-HT1-like receptor in dog saphenous vein (Feniuk et al. 1985; Humphrey et al. 1988). Consistent with this, 5-HT effects were resistant to blockade by the selective 5-HT3 receptor antagonist MDL72222 (1.0 mumol/l). In contrast, methiothepin (0.01-0.3 mumol/l), ketanserin (0.3-30.0 mumol/l) and spiperone (0.3-30.0 mumol/l) each produced surmountable antagonism which, although competitive in nature only for methiothepin (pKB = 9.45 +/- 0.09, 17 d.f.), implied 5-HT2 receptor involvement. The possibility that these discrepancies resulted from mixed populations of 5-HT1-like and 5-HT2 receptors can be excluded because; 1). Ketanserin and spiperone blocked the actions of 5-HT and the selective 5-HT1-like receptor agonist GR43175 with equal facility and 2). Responses to all of the agonists studied were similarly antagonised by flesinoxan (pKB approximately 6.4), a simple competitive antagonist at the receptor in rabbit saphenous vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Actions of non-peptide ergot alkaloids at 5-HT1-like and 5-HT2 receptors mediating vascular smooth muscle contraction.

This report describes the actions of the non-peptide ergot alkaloids methysergide, methylergometrine and ergometrine at two types of 5-HT receptor mediating vascular contraction; the well established 5-HT2 receptor in rabbit aorta and a non-5-HT2 receptor in rabbit saphenous vein which resembles the 5-HT1-like receptor in dog saphenous vein. In the rabbit aorta ergometrine (1 mumol/l) and methylergometrine (0.3 mumol/l), but not methysergide, produced small contractions (14% and 7% respectively of the maximal response to 5-HT). This contraction was not related to activation of 5-HT2 receptors since it was resistant to blockade by ketanserin (0.3 mumol/l). When examined as antagonists of 5-HT-induced contractions of rabbit aorta, each ergot displayed nanomolar affinity at the 5-HT2 receptor but only methysergide behaved as a simple competitive antagonist (pKB = 8.25). Methylergometrine and ergometrine produced surmountable blockade which was accompanied by a non-parallel displacement of the 5-HT concentration-effect curves. The selective 5-HT1-like receptor agonist GR43175 (less than or equal to 30 mumol/l) was devoid of affinity at the 5-HT2 receptor in rabbit aorta. In the rabbit saphenous vein each of the ergots produced concentration-dependent contractions which resulted in overtly biphasic concentration-effect curves. Only the first phase of contraction mimicked the effects of 5-HT and GR43175 since contractions were not blocked by MDL 72222 (1 mumol/l), but were surmountably antagonised by methiothepin (10 nmol/l), ketanserin (0.3 mumol/l) and spiperone (0.3 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effects of the 5-HT1 receptor agonists DP-5-CT, CGS 12066B, and RU 24969 on plasma adrenaline and glucose levels in the rat.

Recent results have indicated that the 5-HT1A receptor subtype mediates the adrenaline-releasing and hyperglycemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. The aim of this study was to analyse, by means of the peripherally acting 5-HT1A receptor agonist, N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT), whether these 5-HT1A receptors are peripherally or centrally localised. In view of the appreciable affinity of DP-5-CT for the 5-HT1D receptor subtype, the effects of the mixed 5-HT1B/5-HT1D receptor agonist 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline (CGS 12066B), and the mixed 5-HT1A/5-HT1B/5-HT1D receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridine-4-yl)1H-indole (RU 24969) were also investigated. Administration of DP-5-CT (0.3 and 1 mg/kg i.v.) increased plasma glucose levels dose-dependently, whereas only the 1 mg/kg dose of DP-5-CT elicited a rise in plasma adrenaline levels. In contrast, CGS 12066B (1.5 and 4.5 mg/kg i.v.) did not affect either plasma adrenaline or plasma glucose levels. Administration of RU 24969 (0.5-4.5 mg/kg i.v.) increased dose-dependently both plasma adrenaline and glucose levels. The data suggest that central 5-HT1A receptors, but neither 5-HT1B nor 5-HT1D receptors, regulate plasma adrenaline and glucose levels.

Animals↗
PubMed1990

Isolation of cDNAs encoding four mouse FGF family members and characterization of their expression patterns during embryogenesis.

To initiate a study of the role of the fibroblast growth factor (FGF) family in mammalian development, we have isolated cDNAs encoding four mouse FGF family members, aFGF, bFGF, kFGF, and FGF-5. This was achieved by a process that circumvents the use of cDNA libraries: for each family member, a cDNA fragment containing the conserved portion of the coding region was amplified from a pool of embryonic and teratocarcinoma cell cDNAs using the polymerase chain reaction (PCR) and cloned; the remaining coding sequences 5' and 3' to the conserved region were cloned using the RACE method. The cDNA clones obtained were used as probes to analyze the expression of these genes at the RNA level in teratocarcinoma cells and embryos at 10.5 to 17.5 days of gestation. Fgfk appears to be specific to undifferentiated teratocarcinoma stem cells. Fgf5 transcripts were detected at every stage and in every tissue tested, but showed a dramatic 15-fold increase in abundance as teratocarcinoma stem cells differentiated to simple embryoid bodies. Fgfb expression showed the greatest tissue-specific variability in abundance, with the highest levels detected in the developing limbs and tail. Fgfa showed the least variable pattern of expression, with transcripts detected at roughly equivalent levels in almost all samples analyzed. On the basis of these data we speculate on some possible roles that the different FGF family members may play in the developing embryo.

Amino Acid Sequence↗
PubMed1990

Estimation of agonist affinity and efficacy by direct, operational model-fitting.

A few years ago Black and Leff (1983) presented a theoretical model for agonist action that can be fitted directly to experimental agonist concentration-effect data in order to estimate affinities and relative efficacies of agonists. The model has been successfully applied to data obtained using experimental designs commonly employed in pharmacologic experiments. This article describes the methodology used to fit the model equations to data for full and partial agonists, shows how affinity and efficacy estimates are calculated for these values, and shows how experimental design influences these calculations.

Models, Biological↗
PubMed1990

Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extra-toes (Hx) on chromosome 5.

The mouse genome contains two genes, En-1 and En-2, with sequence similarity to the engrailed gene of Drosophila. Using conventional linkage crosses, we have shown that En-1 maps approximately 0.28 cM distal to the dominant hemimelia (Dh) gene on chromosome 1 and that En-2 maps approximately 1.1 cM proximal to the hemimelic extra-toes (Hx) gene on chromosome 5. We have also shown by Northern blot analysis that En-1 transcripts in Dh homozygotes and En-2 transcripts in Hx homozygotes are of normal size and abundance. These data, in conjunction with previously published studies of the patterns of En-1 and En-2 expression in developing mouse embryos, suggest that Dh and Hx are very unlikely to be mutant alleles of En-1 or En-2, respectively. Instead, we suggest that En-1-Dh and En-2-Hx represent paralogous linkage groups that evolved following duplication of a common ancestral chromosome segment.

Animals↗