Bad example.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J F Martin
Publications and source records attributed to J F Martin.
Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor.
13 women admitted consecutively in preterm labour were recruited to an observational study of the effect of glyceryl trinitrate (GTN) patches on uterine contractions and prolongation of pregnancy. All twenty episodes of preterm labour (at 23-33 weeks' gestation) responded. 1 patient delivered because of cervical incompetence despite cessation of uterine contractions. The mean prolongation of pregnancy was 34 days. 8 babies have been born so far, and are progressing well. GTN patches appear to be a safe, well-tolerated, and non-invasive method of suppressing uterine contractions in preterm labour.
Administration, Cutaneous↗
Expression of the Streptomyces griseus alpha-amylase gene in Escherichia coli.
The amy gene of Streptomyces griseus was not expressed in Escherichia coli cells due to the lack of recognition of the amy promoter by the E. coli RNA polymerase, as confirmed by using promoter-probe vectors. The expression of the amy gene in E. coli was detected only when the promoter-less gene was placed under the control of the lacZ promoter and was dependent on the level of IPTG added to the medium. The extracellular alpha-amylase detected in the culture broth seems to be released by cellular lysis. When the amy gene lacking both leader peptide and promoter was transcribed from the lacZ promoter, no alpha-amylase activity was detected but larger E. coli cells and inclusion bodies were observed.
Amino Acid Sequence↗
Interdependence of gene expression for early steps of cephalosporin synthesis in Streptomyces clavuligerus.
The early steps of cephamycin synthesis by S. clavuligerus are catalyzed sequentially by lysine epsilon-aminotransferase (LAT), delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthase (cyclase, IPNS). The genes (lat, pcbAB, and pcbC, respectively) are closely linked in the same order as the enzymes act in the biosynthetic pathway and are transcribed in the same direction. Four cephamycin non- (or low-) producing mutants are pleiotropic in that they have undetectable or markedly diminished levels of ACVS and cyclase; two mutants almost completely lack LAT activity. All four mutants are complemented in cephamycin formation by transformation with pNBR1, a plasmid containing a 7.2-kb genomic region of S. clavuligerus in vector pIJ702. The cloned DNA was found to possess no part of the cyclase gene, but instead it contained lat and the 5' upstream part of pcbAB. Doran et al. reported that the 31-bp region between pcbAB and pcbC contains no recognizable promoter or transcription termination sequences. We found that there are 153 bp between the lat ORF and the pcbAB start codon. A potential transcriptional terminator begins 4 to 6 bp downstream of the lat ORF. In the 111-bp segment between the end of the "terminator" and the pcbAB start codon, there are no Streptomyces-like or Escherichia coli-like promoter consensus sequences. However, upstream of the "terminator," that is, in the downstream portion of the lat ORF, are two regions resembling a Streptomyces consensus promoter. Promoter activity in gene fusion constructions was demonstrated in this region. A third potential promoter is upstream of the lat ORF, but only the--10 part is on the cloned DNA. The mechanism by which the cloned DNA (containing lat, the 5' part of pcbAB, and the intervening sequence) influences the expression of the downstream genes encoding ACVS and IPNS, even in strains that possess LAT activity, is an intriguing target of future investigation.
Cephalosporins↗
The expression pattern of the chick homeobox gene gMHox suggests a role in patterning of the limbs and face and in compartmentalization of somites.
MHox is a homeodomain protein that binds an essential element in the core of the muscle creatine kinase enhancer. In the mouse embryo, MHox expression is restricted to mesenchymal cells; in adult mice the gene is highly expressed in skeletal and cardiac muscle. To further define the functions of MHox during embryogenesis, we have cloned its chicken homolog, termed gMHox, and analyzed its properties and detailed expression patterns. Our studies show that the amino acid sequence and DNA-binding properties of the avian and murine gene products are very similar. Furthermore, the sites of expression are alike with high levels of expression in the splanchnic mesoderm, in the somatic mesoderm, in the limb bud mesoderm, in the dermatome and in the dermis, and in the ectomesenchyme of the face. gMHox became downregulated as chondrogenesis proceeded, whereas its expression was maintained in perichondrium and undifferentiated mesenchymal cells beneath the surface ectoderm. Such a pattern of expression suggests that gMHox may participate in maintenance of mesenchymal cell lineages derived from both mesoderm and the neural crest and in patterning of the limbs and the face. Removal of the surface ectoderm overlying the somites has no visible effect on the architecture of somites but results in the failure of gMHox to be expressed in the underlying dermatome, suggesting that regulation of gMHox expression in these cells is dependent on cues emanating from the surface ectoderm.
Amino Acid Sequence↗
Fuzzy control in anesthesia.
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Anesthesia↗
The adventitia and atherogenesis: removal initiates intimal proliferation in the rabbit which regresses on generation of a 'neoadventitia'.
Removal of the carotid artery adventitia from rabbits induced the formation of an intimal hyperplastic lesion. In rabbits fed a normal diet, the lesion (measured as the intimal:medial ratio) was maximal by day 14 (0.456 +/- 0.079, n = 5, P < 0.01) and thereafter, regressed towards control dimensions (0.037 +/- 0.003, n = 14) by day 28 (0.080 +/- 0.025, n = 7, P = 0.14). In rabbits fed a high cholesterol diet, the lesion was again maximal by day 14 (0.376 +/- 0.056, n = 8, P < 0.01). Although some regression was seen, the lesion persisted to day 42 (0.272 +/- 0.052, n = 8, P < 0.01). Electron microscopy and immunocytochemistry showed two types of lesion, (a) smooth muscle cell predominant on normal diet and, (b) macrophage predominant on high cholesterol diet. Smooth muscle cell predominant lesions underwent almost complete regression, whereas macrophage predominant lesions persisted. We propose that lesion formation may be initiated following the development of arterial wall hypoxia, secondary to excision of the adventitial vasa vasorum. Furthermore, we have devised a novel method to restore a highly vascular 'neoadventitia' to an artery whose adventitia has previously been removed, using loosely placed PVC tubing. We suggest this 'neoadventitia' was able to inhibit the formation of an intimal hyperplastic lesion and to promote regression of an already established lesion by restoring arterial wall oxygenation.
Animals↗
Endogenous mediators and thrombophilia.
Platelet function is a balance between factors determined at thrombopoiesis and prothrombotic and antithrombotic mediators from the vascular wall. Nitric oxide is a crucial vasodilator and inhibitor of platelet activation synthesized constitutively by the vascular endothelium. In some pathological states this synthesis may be impaired leading to a prothrombotic state. In other situations, synthesis may be increased by a second inducible enzyme. Nitric oxide synergizes with other antithrombotic vasodilators such as prostacyclin and is opposed by prothrombotic vasoconstrictor mediators such as thromboxane. Platelets are anucleate and their reactivity is partly determined at thrombopoiesis by their progenitor cell, the megakaryocyte. In thrombotic states, such as myocardial infarction, larger, more reactive platelets from larger megakaryocytes are observed.
Animals↗
Animal experiments are useful and necessary in understanding cardiovascular disease.
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Animal Rights↗
Megakaryocyte DNA content is increased in patients with coronary artery atherosclerosis.
OBJECTIVE: Increased megakaryocyte size and megakaryocyte ploidy have been observed in man following myocardial infarction and sudden cardiac death. The aim of this study was to compare megakaryocyte ploidy in patients with and without coronary artery atherosclerosis. METHODS: Sternal megakaryocytes were obtained immediately prior to cardiac surgery in 26 patients with significant coronary artery atherosclerosis requiring surgical bypass grafting and in 14 age matched control patients requiring cardiac valve replacement or repair with minimal or no coronary atherosclerosis on arteriography. Megakaryocytes were identified using a monoclonal antibody to the CD41 (GPIIb/IIIa) surface antigen and ploidy was studied using flow cytometry. RESULTS: Megakaryocyte modal ploidy was significantly higher in the coronary atherosclerosis patients (modal ploidy 8N, n = 0 subjects; 16N, n = 16; 32N, n = 10) as compared with the control group (modal ploidy 8N, n = 5 subjects; 16N, n = 7; 32N, n = 2), p = 0.008. Ploidy correlated with the degree of coronary atherosclerosis defined as the number of atherosclerotic vessels observed on angiography (r = 0.51, p < 0.001, 95% confidence limits 0.25 to 0.70) and the serum total cholesterol concentration (r = 0.50, p = 0.006, 95% confidence limits 0.18 to 0.72). Bleeding time was not different [315(semiquartile range 45) s v 315(75) s] between the two groups in spite of the fact that 20 of 26 coronary atherosclerosis patients were taking aspirin versus one of 14 valve patients. CONCLUSIONS: Megakaryocyte ploidy is increased in human coronary atherosclerosis and correlates with serum lipids. Hypercholesterolaemia may induce increases in megakaryocyte ploidy, and hence the production of hyperfunctional platelets, which will contribute to atherogenesis.
Cholesterol↗
Application of pattern recognition and image classification techniques to determine continuous cardiac output from the arterial pressure waveform.
The shape of the arterial pressure waveform is a non-linear function of stroke volume, heart rate and many other cardiovascular parameters. Previous attempts have been made to exploit this relationship and derive cardiac output (CO) from the arterial pressure waveform. These classical "pulse-contour" methods utilized simplifying linear assumptions, as a result they failed to adequately estimate CO over a sufficiently wide range of hemodynamic conditions. We have applied pattern recognition and image processing techniques to the problem of deriving CO from the arterial pressure waveform, thereby eliminating the need for simplifying assumptions. Computer simulations were used to develop the basic pattern recognition algorithms and compare their performance with that of published classical "pulse-contour" methods. Animal models were subsequently used to demonstrate proof of the concept. For over 200,000 individual heart beats, covering a wide range of hemodynamic conditions, the mean error, in calculated CO compared to ultrasonic flow probe determined CO, was 2.8% with a standard deviation of 9.8%.
Algorithms↗
Punctuated equilibrium in evolution and the platelet.
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Animals↗
Platelet glycoprotein IIb-IIIa and size are increased in acute myocardial infarction.
Platelet aggregation, which plays an important role in acute myocardial infarction (AMI), is mediated by fibrinogen binding to the platelet membrane glycoprotein (GP)IIb-IIIa (CD41). This study measured the relative number of GPIIb-IIIa complexes on platelets from patients immediately following AMI (n = 14) compared with those from controls (n = 14). Flow cytometry was used to demonstrate that there were, on average, 20% more GPIIb-IIIa complexes on platelets after AMI compared with controls. Platelet size was also 7% greater in AMI and it is known that larger platelets are more reactive. Since platelet size and protein content are determined at thrombopoiesis the majority of these platelets must have been circulating prior to AMI. Larger platelets, with more GPIIb-IIIa may, therefore, be causally related to AMI.
Aged↗
A nitric oxide donor improves uterine artery diastolic blood flow in normal early pregnancy and in women at high risk of pre-eclampsia.
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Adaptation, Physiological↗
The megakaryocyte platelet system and vascular disease.
Platelets form a heterogeneous population of cells produced from the uniquely large polyploid cell found in the bone marrow, the megakaryocyte. The platelet megakaryocyte axis forms a dynamic equilibrium varying in normal biology and in disease. Prolonged platelet destruction leads to the production of large platelets from large, high ploidy megakaryocytes. In vivo and ex vivo studies show that such platelets have more haemostatic potential than smaller less dense platelets. The evidence suggesting that prothrombotic changes in the megakaryocyte platelet axis precede coronary artery thrombosis and the importance of platelet reactivity in atherosclerosis will be reviewed.
Arteriosclerosis↗
Catabolism of lysine in Penicillium chrysogenum leads to formation of 2-aminoadipic acid, a precursor of penicillin biosynthesis.
Penicillium chrysogenum L2, a lysine auxotroph blocked in the early steps of the lysine pathway before 2-aminoadipic acid, was able to synthesize penicillin when supplemented with lysine. The amount of penicillin produced increased as the level of lysine in the media was increased. The same results were observed in resting-cell systems. Catabolism of [U-14C]lysine by resting cells and batch cultures of P. chrysogenum L2 resulted in the formation of labeled saccharopine and 2-aminoadipic acid. Formation of [14C]saccharopine was also observed in vitro when cell extracts of P. chrysogenum L2 and Wis 54-1255 were used. Saccharopine dehydrogenase and saccharopine reductase activities were found in cell extracts of P. chrysogenum, which indicates that lysine catabolism may proceed by reversal of the two last steps of the lysine biosynthetic pathway. In addition, a high lysine:2-ketoglutarate-6-aminotransferase activity, which converts lysine into piperideine-6-carboxylic acid, was found in cell extracts of P. chrysogenum. These results suggest that lysine is catabolized to 2-aminoadipic acid in P. chrysogenum by two different pathways. The relative contribution of lysine catabolism in providing 2-aminoadipic acid for penicillin production is discussed.
2-Aminoadipic Acid↗
Characterization of a region of plasmid pBL1 of Brevibacterium lactofermentum involved in replication via the rolling circle model.
The minimal region for autonomous replication of pBL1, a 4.5-kb cryptic plasmid of Brevibacterium lactofermentum ATCC 13869 that has been used to construct a variety of corynebacterium vectors, was shown to be contained on a 1.8-kb HindII-SphI DNA fragment. This region contains two open reading frames (ORFs) (ORF1 and ORF5) which are essential for pBL1 replication in B. lactofermentum. Accumulation of single-strand intermediates in some of the constructions indicates that plasmid pBL1 replicates via the rolling circle replication model; its plus strand and minus strand were identified by hybridization with two synthetic oligonucleotide probes complementary to each pBL1 strand. ORF1 seems to encode the Rep protein and showed partial homology with sequences for Rep proteins from Streptomyces plasmids which replicate via rolling circle replication such as pIJ101, pSB24, and pJV1.
Amino Acid Sequence↗
Exogenous methionine increases levels of mRNAs transcribed from pcbAB, pcbC, and cefEF genes, encoding enzymes of the cephalosporin biosynthetic pathway, in Acremonium chrysogenum.
Methionine stimulated cephalosporin production in cultures of three different strains of Acremonium chrysogenum when added either at inoculation time or at 72 h to cells grown previously in the absence of methionine. When methionine was added at 72 h, the stimulation of cephalosporin biosynthesis was observed only 12 h later and required de novo protein synthesis. Methionine increased the levels of enzymes (isopenicillin N synthase and deacetylcephalosporin C acetyltransferase) expressed from genes (pcbC and cefG, respectively) located in the two clusters of cephalosporin biosynthesis genes in the wild-type A. chrysogenum strain and also in the two improved strains, CW19 and C10. Methionine-supplemented cells showed higher levels of transcripts of the four known genes (pcbAB, pcbC, cefEF and, to a slight extent, cefG) of the cephalosporin biosynthetic pathway than cells grown in the absence of methionine. The levels of the cefG transcript were much lower than those of the pcbAB, pcbC, and cefEF transcripts. The induction by methionine of transcription of the four cephalosporin biosynthesis genes and the known effect of this amino acid on the differentiation of A. chrysogenum indicate that methionine exerts a pleiotropic effect that coordinately regulates cephalosporin biosynthesis and differentiation.
Acetyltransferases↗