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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 163 records · Page 9Linked to original sources
PubMed1998

Endothelin-1 induces production of the neutrophil chemotactic factor interleukin-8 by human brain-derived endothelial cells.

Increased levels of endothelin-1 (Et-1), a potent vasoconstrictor, have been correlated with hypertension and neuronal damage in ischemic/reperfusion injury. The presence of polymorphonuclear cells (PMNs) in the brain has been shown to be directly responsible for this observed pathology. To address the question of whether Et-1 plays a role in this process, human brain-derived endothelial cells (CNS-ECs) were cultured with Et-1. The results demonstrate that Et-1 induces production of the neutrophil chemoattractant interleukin-8 (IL-8) twofold to threefold after 72 hours; mRNA was maximal after 1 hour of stimulation. Conditioned culture medium derived from Et-1-stimulated CNS-ECs induced a chemotactic response in the PMN migration assay. The inflammatory cytokines tumor necrosis factor-alpha (TNF) and IL-1beta functioned additively with Et-1 in increasing IL-8 production. In contrast, transforming growth factor-beta (TGF-beta), but not IL-10, completely abolished the effect of Et-1 on IL-8 production. However, Et-1 did not modulate intercellular adhesion molecule-1 (ICAM-1) expression. These data demonstrate that Et-1 may be a risk factor in ischemic/reperfusion injury by inducing increased levels of the neutrophil chemoattractant IL-8.

Brain Ischemia↗
PubMed1998

The small-eye mutation results in abnormalities in the lateral cortical migratory stream.

Mice with homozygous mutations of the Pax-6 gene exhibit a constellation of developmental problems including the absence of eyes and nasal cavities and problems in the movement of neuroblasts out of the germinal epithelium. In this paper, we demonstrate further disturbances in neuronal migration. Normally, cells produced along the lateral ventricles move laterally across the pallium, ultimately coming to reside in the lateral neocortex and primary olfactory cortex. In mutant animals, these cells continue to migrate to the pial surface of the brain.

Animals↗
PubMed1998

Measurement of thrombomodulin mRNA expression in brain capillaries by polymerase chain reaction.

Thrombomodulin (TM), an endothelial integral membrane protein, is a potent activator of the protein C anticoagulant pathway. TM protein expression is limited and regionally distributed in the brain. Recent investigations have demonstrated low TM mRNA expression by brain endothelium, corresponding to its distribution at the protein level. To facilitate the study of TM expression at the transcriptional level, we measured TM mRNA by quantitative-competitive polymerase chain reaction (QC-PCR) and by standard densitometric analysis of reverse transcriptase-PCR products (RT-PCR) in different regions of bovine brain. QC-PCR demonstrated differential TM mRNA expression in the pons (100+/-9%), cerebellum (359+/-103%), and cortex (441+/-24%). We compared these results with those of RT-PCR and found similar differences in relative TM mRNA expression in the pons (100+/-44%), cerebellum (343+/-8%), and cortex (404+/-62%). Data derived by QC-PCR and RT-PCR were highly correlated (r=0.99, p<0.03). These findings indicate that either QC-PCR or RT-PCR can be used to accurately quantify TM mRNA.

Animals↗
PubMed1998

Iron uptake by the halotolerant alga Dunaliella is mediated by a plasma membrane transferrin.

A 150-kDa transferrin-like protein (Ttf) is associated with the plasma membrane of the halotolerant unicellular alga Dunaliella salina (Fisher, M., Gokhman, I., Pick, U., and Zamir, A. (1997) J. Biol. Chem. 272, 1565-1570). The Ttf level rises with medium salinity or upon iron depletion. Evidence that Ttf is involved in iron uptake by Dunaliella is presented here. Algal iron uptake exhibits characteristics resembling those of animal transferrins: high specificity and affinity for Fe3+ ions, strict dependence on carbonate/bicarbonate ions, and very low activity in acidic pH. Reducing the level of Ttf by mild proteolysis of whole cells is accompanied by lowered uptake activity. Conversely, accumulation of high levels of Ttf is correlated with an enhancement of iron uptake. Kinetically, iron uptake consists of two steps: an energy-independent binding of iron to the cell surface and an energy-dependent internalization. Salinities as high as 3.5 M NaCl do not inhibit iron uptake or decrease the apparent affinity for Fe3+ ions, implying that Ttf activity is not affected by high salt. These results indicate that transferrins, hitherto identified only in animals, are present and function in iron transport also in plant systems.

Cell Membrane↗
PubMed1998

Employment of a phenoxy-substituted acridinium ester as a long-lived chemiluminescent indicator of glucose oxidase activity and its application in an alkaline phosphatase amplification cascade immunoassay.

This paper describes the employment of a novel phenoxy-substituted acridinium ester (di-ortho-bromophenyl-AE) as a chemiluminescent endpoint indicator for ligand binding assays. The reactivity of this compound is such that it is capable of generating a high-intensity chemiluminescent signal at neutral pH. Under these conditions, when present in excess, it has been used as an indicator of hydrogen peroxide generation by the action of glucose oxidase (GOx, EC 1.1.3.4) on glucose substrate. The resulting chemiluminescent signal is a long-lived glow. The magnitude of the chemiluminescent signal is directly proportional to the quantity of GOx present and has been used to measure GOx with a sensitivity of 1.8 x 10(-16) mol. In addition, this ability to monitor GOx activity has been utilized in an alkaline phosphatase (ALP, EC 3.1.3.1) amplification cascade assay. Here ALP catalyzes the formation of FAD from a prosthetogenic substrate FADP. FAD, a cofactor for a number of oxidase enzymes, then converts inactive apo-GOx to holo-GOx, the activity of which is monitored by the chemiluminescent endpoint and facilitates detection of ALP over the range 10(-15) to 4.1 x 10(-19) mol. The clinical utility of this system has been demonstrated by application to the assay of human thyrotrophin (TSH, sensitivity 0.005 mU/liter).

Acridines↗
PubMed1998

Crystallization of the NADP-dependent beta-keto acyl carrier protein reductase from Escherichia coli.

The NADP-dependent beta-keto acyl carrier protein reductase (BKR) from E. coli has been crystallized by the hanging-drop method of vapour diffusion using poly(ethylene glycol) of average molecular weight 1450. The crystals belong to the hexagonal space group P6122 or P6522 with unit-cell dimensions a = b = 67.8, c = 355.8 A. Calculated values for Vm and consideration of the packing suggest that the asymmetric unit contains a dimer. BKR catalyses the first reductive step in the elongation cycle of fatty-acid biosynthesis. It shares extensive sequence homology with the enzyme which catalyzes the second reductive step in the cycle, enoyl acyl carrier protein reductase (ENR), and thus provides an opportunity to study the evolution of enzyme function in a metabolic pathway. The structure determination will permit the analysis of the molecular basis of its catalytic mechanism and substrate specificity.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗
PubMed1998

Does bilateral internal thoracic artery grafting increase surgical risk in diabetic patients?

BACKGROUND: The purpose of this study was to determine whether, with appropriate techniques, diabetic patients could benefit from the advantages of double internal thoracic artery (ITA) coronary bypass without an increased hospital risk. METHODS: Between January 1990 and December 1996, 207 consecutive diabetic patients underwent coronary artery bypass graft operations. In 74 patients both arteries (bilateral ITA group) were used, whereas 133 patients received one ITA and vein grafts or vein grafts alone (nonbilateral group). Patients in the bilateral ITA group were younger (p<0.0001), predominantly male (p<0.0001), and were operated on more electively. The internal thoracic arteries were harvested by skeletonization without electrocautery, and strict glycemic control was pursued. RESULTS: No death was observed in the bilateral ITA group, whereas 7 patients died in the nonbilateral ITA group (p<0.05). Deep sternal wound infection was observed in 2 patients in the nonbilateral ITA group (1.5%) and in none of the bilateral ITA group (p = NS). There was no significant difference in the morbidity rate between the two groups except for greater blood losses in the bilateral ITA group. CONCLUSION: Double ITA coronary revascularization in young diabetic patients was performed without increased morbidity and mortality. The low rate of sternal wound infections may be related to ITA harvesting by a skeletonization technique, but larger studies are required to confirm these data.

Case-Control Studies↗
PubMed1998

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Filtering Surgery↗
PubMed1998

Breakdowns on the path of chronic illness: opportunities for learning.

An unusual case of calciphylaxis, presenting at the onset of end-stage renal disease and evolving into an extended and arduous hospital stay, is described. The medical approach to this case is addressed briefly, but the main focus of this paper is to describe, in the words of various participants, the events and interactions that occurred and to learn from this description how our management of such cases breaks down. When confronted by difficult circumstances, it is common for us to react emotionally in ways that are automatic and based on our own personal histories and behavior patterns. Such automatic reactions prevent us from seeing and understanding what we really need to know about a given situation and leave us vulnerable to discouragement and internal suffering when clinical events do not go well (A. Nierenberg, personal communication, April 1998). The result is often exasperation with patients and families, as well as emotionally laden interactions that do not forward problem solving. In retrospect, the appearance of such breakdowns is not only predictable in the course of chronic illness, but offers us the opportunity to observe our automatic reactions, to re-evaluate our approach, and to redesign our actions. We have written this review, not to find error or blame, but rather to emphasize that we are learning to view these breakdowns as signals first to step back from our automatic reactions and then to listen and communicate clearly as a means to navigating the best pathway through difficult and discouraging clinical challenges.

Calciphylaxis↗
PubMed1998

Identification of mutations in the human PATCHED gene in sporadic basal cell carcinomas and in patients with the basal cell nevus syndrome.

Mutations in PATCHED (PTC), the human homolog of the Drosophila patched gene, have been identified in most exons of the gene in patients with the basal cell nevus syndrome and in sporadic basal cell carcinomas. We have screened the 23 PTC exons for mutations using single strand conformation polymorphism analysis of DNA from 86 basal cell nevus syndrome probands, 26 sporadic basal cell carcinomas, and seven basal cell nevus syndrome-associated basal cell carcinomas. This screen identified mutations located in eight exons in 13 of the basal cell nevus syndrome patients and in three of the tumors. The most common mutations were frameshifts resulting in premature chain termination. These results provide further evidence for the crucial role of PTC as a tumor suppressor in human keratinocytes.

Amino Acid Substitution↗
PubMed1998

Mivacurium compared with succinylcholine in children with liver disease.

We have compared mivacurium and succinylcholine in 27 paediatric patients with mild (Child's A) to moderate (Child's B) liver disease undergoing oesophagogastroduodenoscopy (OGD) and injection of oesophageal varices, with 10 healthy children receiving mivacurium for ENT procedures. With mivacurium 0.2 mg kg-1, the severity of liver disease did not correlate with duration of block compared with controls (time from bolus to T1 25%, P = 0.74; T1 25% to T4:T1 > 0.7, P = 0.545). However, initial recovery (time to T1 25%, P = 0.002) and overall recovery (bolus to T4:T1 > 0.7, P = 0.004) from mivacurium-induced neuromuscular block correlated inversely with pre-existing concentrations of plasma cholinesterase. Conditions for tracheal intubation at 2 min with mivacurium were comparable with conditions at 1 min with succinylcholine in the liver patients.

Child↗
PubMed1998

Astrocyte regulation of endothelial tissue plasminogen activator in a blood-brain barrier model.

Expression of tissue plasminogen activator (tPA) substantially determines endothelial-dependent fibrinolysis. We used a blood-brain barrier (BBB) model to analyze regulation of brain capillary endothelial tPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). This model consists of coculture of murine astrocytes with bovine brain capillary endothelial cells grown as capillary-like structures (CS); after 1 week, astrocytes become extensively associated with CS, and the BBB-associated enzyme gamma-glutamyl transpeptidase is present. We measured tPA and PAI-1 mRNA and tPA activity in this model. Reverse transcription-polymerase chain reaction (RT-PCR) studies showed similar tPA and PAI-1 mRNA levels after 1 day mono-culture (endothelial cells only) versus astrocyte-endothelial coculture preparations. After 7 days (i.e., when elements of the BBB are present), astrocyte-endothelial cocultures (compared with endothelial mono-cultures) showed a 50.7%+/-27.1% (mean +/- SD) reduction in tPA mRNA (P < 0.03) and a 183.3%+/-86.9% increase in PAI-1 mRNA expression (P < 0.02). Moreover, 7-day cocultures demonstrated reduced tPA activity compared with mono-cultures (14.6+/-2.9 IU/mL versus 30.2+/-7.7 IU/mL, P < 0.01); 1-day cocultures and mono-cultures had similar tPA activity. These findings demonstrate that astrocytes regulate brain capillary endothelial expression of tPA when elements of the BBB phenotype are present in this model. These data suggest an important role for astrocytes in the regulation of brain capillary endothelial fibrinolysis.

Animals↗