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Biomedical subjects

G R Martin

Publications and source records attributed to G R Martin.

At least 253 records · Page 14Linked to original sources
PubMed1986

[Piperacillin in the newborn infant. A clinical and pharmacologic study].

The study involved 70 neonates born at 27 to 48 weeks of pregnancy (mean: 34.2 weeks) and weighing between 840 and 4350 g (mean: 1860 g). In every case piperacillin was combined with an aminoglycoside. The infants were treated for materno-foetal infection (14), post-partum infection (19), enterocolitis (18, surgical in 9 cases) and other post-operative infections (19). The antibiotic combination was given prophylactically in 2 cases. Fifty micro-organisms were isolated in 39 patients: 24 from blood (hemoculture), 2 from CSF, 24 from multiple peripheral samples. There were 13 Gram-positive organisms (Streptococcus B, D, A, Listeria spp.) and 37 Gram-negative organisms (E. coli 14, Klebsiella spp. 10, Enterobacter spp. 6). Clinical and bacteriological cure was obtained in 67 patients. Three failures were recorded, with resistance to treatment of Klebsiella pneumoniae and emergence (at hemoculture) of Klebsiella oxytoca under treatment in one patient and of Enterobacter cloacae in another patient. A pharmacokinetic study was performed in 47 neonates. Piperacillin (75 mg/kg per dose) was given twice a day until the 8th day post-partum and three times a day subsequently. The antibiotic was administered either by 30-min infusions or by intravenous or intramuscular injections; 124 serum level measurements were carried out at peak and/or residual level. In 44 infants with normal renal and hepatic function the mean residual level was 23 micrograms/ml (range: 7-100 micrograms/ml) and the mean peak level was 119 micrograms/ml (range: 47-278 micrograms/ml). No local or systemic side-effect was noted, and there was no evidence of toxicity.

Bacterial Infections↗
PubMed1986

Transient prolongation of the QTc interval after balloon valvuloplasty and angioplasty in children.

QTc-interval changes were evaluated in 39 children who had undergone balloon dilation procedures. In 30 children who had undergone balloon pulmonary valvuloplasty (BPV), QTc intervals were measured on standard electrocardiograms recorded before and 16 to 24 hours after the procedure and at follow-up during the next 1 to 15 months (mean 7). The QTc interval increased from 0.380 +/- 0.027 second before BPV to 0.429 +/- 0.027 second after BPV (p less than 0.002) and returned to 0.377 +/- 0.026 second at follow-up. To determine when during the catheterization-dilation procedure the QTc interval increased, QTc intervals were measured on monitor electrocardiograms recorded during cardiac catheterization. The baseline QTc was 0.382 +/- 0.041 second, was unchanged after angiography and increased to 0.427 +/- 0.043 second after BPV (p less than 0.002). A similar prolongation occurred in 3 of 4 children who had undergone balloon aortic valvuloplasty and in 4 of 5 who had undergone coarctation angioplasty. In control children, who had undergone catheterization without dilation, QTc was unchanged. Thus, transient increases in QTc interval occur after semilunar valvuloplasty and coarctation angioplasty. These dilation procedures are a cause of QTc prolongation; however, the mechanism is unknown. It is possible that the sudden unilateral increase in afterload affects the myocardium or myocardial sympathetic receptors. Because QTc prolongation may predispose children to the R-on-T phenomenon, postprocedure monitoring appears to be warranted.

Adolescent↗
PubMed1986

Localization of binding sites for laminin, heparan sulfate proteoglycan and fibronectin on basement membrane (type IV) collagen.

Rotary shadowing electron microscopy was used to examine complexes formed by incubating combinations of the basement membrane components: type IV collagen, laminin, large heparan sulfate proteoglycan and fibronectin. Complexes were analyzed by length measurement from the globular (COOH) domain of type IV collagen, and by examination of the four arms of laminin and the two arms of fibronectin. Type IV collagen was found to contain binding sites for laminin, heparan sulfate proteoglycan and fibronectin. With laminin the most frequent site was centered approximately 81 nm from the carboxy end of type IV collagen. Less frequent sites appeared to be present at approximately 216 nm and approximately 291 nm, although this was not apparent when the sites were expressed as a fraction of the length of type IV collagen to which they were bound. For heparan sulfate proteoglycan the most frequent site occurred at approximately 206 nm with a less frequent site at approximately 82 nm. For fibronectin, a single site was present at approximately 205 nm. Laminin bound to type IV collagen through its short arms, particularly through the end of the lateral short arms and to heparan sulfate proteoglycan mainly through the end of its long arm. Fibronectin bound to type IV collagen through the free end region of its arms. Using a computer graphics program, the primary laminin binding sites of two adjacent type IV collagen molecules were found to align in the "polygonal" model of type IV collagen, whereas with the "open network" model, a wide meshed matrix is predicted. It is proposed that basement membrane may consist of a lattice of type IV collagen coated with laminin, heparan sulfate proteoglycan and fibronectin.

Animals↗
PubMed1986

Chondronectin interactions with proteoglycan.

We have investigated whether proteoglycans are involved in the attachment of embryonic chick chondrocytes to type II collagen. Chondroitin sulfate proteoglycan, when added exogenously, promotes the binding of chondronectin, the chondrocyte attachment factor, to type II collagen substrates and thereby stimulates chondrocyte adhesion. Blockage of endogenous proteoglycan synthesis with beta-xylosides prevents chondronectin-mediated chondrocyte attachment, confirming that proteoglycan is required. The intact proteoglycan must be present since chondroitin sulfate glycosaminoglycans did not promote chondronectin-mediated cell attachment but, rather, inhibited it in a dose-dependent manner. This inhibition, however, could be overcome with excess exogenous proteoglycan. Consequently, chondronectin interacts with proteoglycan and then the complex interacts with the collagen substrate and with the cell surface to promote cell adhesion. Further evidence for a direct interaction of chondronectin with the glycosaminoglycan portion of the proteoglycan is the selective binding of chondronectin to dextran-Sepharose, dextran having been shown to inhibit attachment to an extent similar to that of chondroitin sulfate.

Animals↗
PubMed1986

Basement membrane complexes with biological activity.

We have studied the reconstitution of basement membrane molecules from extracts prepared from the basement membrane of the EHS tumor. Under physiological conditions and in the presence of added type IV collagen and heparan sulfate proteoglycan, gellike structures form whose ultrastructure appears as interconnected thin sheets resembling the lamina dense zone of basement membrane. The major components of the reconstituted structures include laminin, type IV collagen, heparan sulfate proteoglycan, entactin, and nidogen. These components polymerize in constant proportions on reconstitution, suggesting that they interact in defined proportions. Molecular sieve studies on the soluble extract demonstrate that laminin, entactin, and nidogen are associated in large but dissociable complexes which may be a necessary intermediate in the deposition of basement membrane. The reconstituted matrix was biologically active and stimulated the growth and differentiation of certain cells.

Animals↗
PubMed1986

Dysphagia lusorum in children.

The association of difficulty in swallowing and an aberrant right subclavian artery is termed dysphagia lusorum. Dysphagia lusorum has been reported not to occur in children. We describe four children who had difficulty swallowing and aberrant right subclavian arteries. Esophageal manometry showed high pulsatile pressure in the area of the aberrant right subclavian artery in each child (12 to 100 mm Hg). Three of the four children underwent surgical correction, and their symptoms resolved. Postoperatively, esophageal manometric findings were normal. We conclude that dysphagia lusorum occurs in children and esophageal manometry shows persistently increased intraesophageal pressure, causing a functional partial obstruction in symptomatic children with dysphagia lusorum.

Cardiac Catheterization↗
PubMed1986

Regulation of cell attachment and cell number by fibronectin and laminin.

We have examined the effect of laminin and fibronectin on the attachment and growth on type IV collagen of a line of mouse epithelial cells and a strain of adult human fibroblasts. Laminin stimulated attachment of the epidermal cells and fibronectin stimulated fibroblast attachment. At high concentrations (100 micrograms/ml), the attachment proteins altered the growth of cells in culture. The epidermal cells grew better in media containing fibronectin-free serum supplemented with laminin. Fibroblasts, on the other hand, grew best in media containing serum supplemented with fibronectin. These data suggest that laminin promotes epithelial cell growth whereas fibronectin promotes fibroblast growth. This observation was confirmed when these cells were cocultured in the presence of the attachment proteins or of their respective antibodies. The mouse epidermal cells grew best when laminin was added to cocultures of fibroblasts and epithelial cells. Fibroblasts grew best in the presence of antibody to laminin and poorly in the presence of antibody to fibronectin. Thus, fibronectin and laminin may participate in the regulation of cell populations in vivo and may be involved in epithelial-mesenchymal interactions.

Animals↗
PubMed1986

Contrast echocardiography in the diagnosis of anomalous left coronary artery arising from the pulmonary artery.

We have demonstrated an anomalous left coronary artery originating from the main pulmonary artery by saline contrast echocardiography. The anomalous vessel was easily identified using contrast injections into the ascending aorta at catheterization and into a radial artery cannula following catheterization. Contrast echocardiography may be useful in the diagnosis of this lesion when two-dimensional and Doppler echocardiography fail to show the anomalous vessel.

Cardiac Catheterization↗
PubMed1986

Total panoramic vision in the mallard duck, Anas platyrhynchos.

The mallard duck has a retinal visual field giving 360 degrees visual coverage in the horizontal plane and a narrow binocular field of approximately uniform width (approximately equal to 20 degrees) extending through 220 degrees from the bill to directly behind the head. Measurement of the optical fields indicate that the binocular retinal field could be considerably larger than actually found. Eye movements are not of sufficient amplitude to abolish binocularity at any elevation.

Animals↗
PubMed1986

Promoter region of the human pro-alpha 1(II)-collagen gene.

We have isolated a genomic clone containing the 5'-terminal portion of the human pro-alpha 1(II)-collagen gene. This clone, HC2C, contains 10 kb of the gene and 6 kb of 5'-flanking sequences. It was selected by cross hybridization using a [32P]DNA probe containing the promoter region of the rat alpha 1(II)-collagen gene. We have determined the nucleotide sequence of the first exon and of 400 bp upstream. There is considerable homology between this human sequence and the corresponding rat sequence. As in the rat, the first exon contains a 155-bp untranslated segment and a 85-bp sequence coding for the signal peptide and a part of the N-propeptide of type-II procollagen. The segment preceding the transcription initiation site contains a conserved 'ATATAA' element, and several similar G + C-rich stretches. As in the rat gene, no 'CAT' element is evident between -70 and -120. We also find the sequence 5'-GTGGTCAGA-3' reported as an enhancer element in both viral and cellular genes, located around -290 bp. A high degree of homology exists between the atypical rat and human promoter structures; however, such homology is absent among the alpha 1(I), alpha 2(I) and alpha 1(III) promoters, which suggests that the unique alpha 1(II) sequences may be related to the specific expression of the alpha 1(II)-collagen gene.

Amino Acid Sequence↗
PubMed1986

In vitro regulation of cartilage matrix assembly by a Mr 54,000 collagen-binding protein.

In cartilage, type II collagen is present as thin, short, randomly oriented fibrils. In vitro, however, type II collagen forms fibrils of large diameter, indicating that additional factors may be involved in the regulation of collagen fibril formation. We have examined extracts of a cartilage-producing tumor for the presence of collagen-binding proteins. In addition to fibronectin and link protein, a Mr 54,000 protein was found to bind to collagen fibrils as well as to native and denatured type II collagen. Immunological studies using antibody against the protein indicate that it is a cartilage matrix protein, not present in bone or in several other tissues. In vitro studies show that the Mr 54,000 protein in combination with cartilage proteoglycan decreases the rate of type II fibril formation and causes the fibrils to be of small diameter (24 +/- 8 nm). These studies indicate that complexes between collagen and proteoglycans mediated by this protein may regulate the assembly of cartilage matrix.

Animals↗
PubMed1986

Use of a reconstituted basement membrane to measure cell invasiveness and select for highly invasive tumor cells.

Malignant cells must traverse basement membranes during their migration to sites distant from the primary tumor. Since basement membranes are thought to be a critical barrier to the passage of tumor cells, we have constructed a model basement membrane-stromal matrix consisting of laminin and type IV collagen reconstituted onto a disk of type I collagen for use in an in vitro assay of invasiveness. Metastatic tumor cells and leukocytes are able to cross this barrier, whereas nonmetastatic tumor cells, fibroblasts, and epidermal cells cannot penetrate it. Those tumor cells that penetrate the barriers were found, when isolated and subcultured, to be more invasive and to produce more metastases than the parental population. This assay system should be useful for studying the invasiveness of tumor cells and for isolating highly invasive variants.

Animals↗
PubMed1986

Two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development.

The int-1 and int-2 genes were first isolated as targets for transcriptional activation by proviral insertion mutations in mammary carcinomas induced by the mouse mammary tumor virus (MMTV). Since these proto-oncogenes are not expressed at detectable levels in previously tested normal tissues from adult mice, we sought to determine whether these genes might be active during embryogenesis by examining mouse embryos and cultured teratocarcinoma cells for RNA encoded by int-1 and int-2. A single size class of int-1 RNA is present only at mid-gestation stages of development (days 8 through 13) and is also detected in testes from postpuberal mice. Four species of int-2 RNA are found in peri-implantation embryos and teratocarcinoma cells and are particularly abundant in derivatives of the primitive endodermal lineage, but int-2 RNA is not detected during mid- or late gestation or in any normal adult tissues tested. Thus, these two proto-oncogenes, activated during mammary carcinogenesis by the same mechanisms, are normally expressed at different times and places in embryonic and adult mice.

Animals↗
PubMed1986

17 beta-estradiol regulates and v-Ha-ras transfection constitutively enhances MCF7 breast cancer cell interactions with basement membrane.

The interaction of a line of human breast carcinoma cells (MCF7) with basement membrane components, particularly laminin, was altered by exposure of the cells to estrogen as well as by transfection of the cells with the v-Ha-ras oncogene. In both cases, the cells show a greater ability to attach to a laminin substrate, to migrate to laminin, to grow in the presence of a basement membrane matrix, and to cross barriers of reconstituted basement membrane. These responses were associated with an increase in the expression of laminin receptors. It is postulated that the increase in the invasive behavior of the cells treated with estrogen or transfected with v-Ha-ras is related to the increased number of laminin receptors and their interaction with laminin. Estrogen had no discernible effect on the v-Ha-ras transfected cells. It appears that in the MCF7 cells, the malignant phenotype is under hormonal control and that this control is bypassed after v-Ha-ras transfection.

Basement Membrane↗
PubMed1986

Pharmacological analysis of the interaction between Bay K 8644 and 5-HT in rabbit aorta.

Bay K 8644 potentiated and augmented 5-hydroxytryptamine (5-HT)-induced contractions in the rabbit, isolated aorta preparation, as manifested in leftward shift and increase in the asymptote of 5-HT E/[A] (effect vs concentration) curves. The operational model of agonism (Black & Leff, 1983) was used to analyse this interaction and the concomitant effects of irreversible receptor alkylation by phenoxybenzamine. The competitive effects of spiperone in the presence and absence of Bay K 8644 were also examined. From these analyses it is concluded that Bay K 8644 elicits its potentiating effects by increasing the efficacy of 5-HT at the 5-HT2 receptor with no alteration in affinity. This is consistent with the known effect of Bay K 8644 of causing an increase in the functional concentration of plasmalemmal calcium channels coupled to the 5-HT2 receptors in this preparation. The positively co-operative shape of the 5-HT E/[A] curves obtained in the aorta and the quantitative nature of their potentiation by Bay K 8644 indicated that the coupling of 5-HT2 receptor occupancy to intracellular calcium concentration is linear and that the co-operativity resides in the subsequent relation between intracellular calcium and pharmacological effect. Bay K 8644 may serve as a probe for differentiating between the types of calcium channels that transduce 5-HT receptor-mediated effects in different systems. Such information would be useful in the classification of agonist interactions with 5-HT receptors.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Peripheral 5-HT2-like receptors. Can they be classified with the available antagonists?

Interactions between 5-hydroxytryptamine (5-HT) and the so-called 5-HT2 receptor antagonists ketanserin, spiperone, trazodone and methysergide were studied in isolated preparations of the rabbit aorta, rat jugular vein, and rat caudal artery. Trazodone and spiperone were apparently simple competitive antagonists since they produced antagonism that was surmountable over the concentration range studied and, in each tissue, their apparent affinity appeared to be independent of the antagonist concentration. Furthermore, concentration-ratios obtained with the two antagonists in combination suggested that antagonism was additive, implying mutual competition with a single population of 5-HT receptors. Ketanserin was a non-surmountable antagonist of 5-HT in the rat caudal artery and methysergide demonstrated surmountable, competitive antagonism only in the rabbit aorta. Antagonist dissociation constants estimated for apparently competitive interactions showed that ketanserin, spiperone and trazodone expressed affinities which differed according to the tissue used. In the case of trazodone, affinity estimates differed by as much as 12 fold. These discrepancies were independent of the 5-HT receptor agonist used and could not be attributed to an inadequate equilibration of the antagonist. These results can be interpreted in two ways: either the receptors in the different tissues are heterogeneous or the antagonists used here must be considered as unreliable probes for the classification of 5-HT2-like receptors.

Animals↗