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Biomedical subjects

A May

Publications and source records attributed to A May.

At least 163 records · Page 9Linked to original sources
PubMed1996

[PET and Doppler sonography in headaches].

Whether the primary mechanisms of migraine are vascular or neurogenic is, as yet unresolved. Early studies using Doppler sonography prompted heterogeneous results, mainly due to methodological differences. However, blood flow measurements using single photon emission tomography (SPECT) or positron emission tomography (PET) have not revealed any differences in cerebral blood flow in migraine without aura. Moreover, specific migraine compounds do not alter cortical blood flow. During attacks, increased blood flow is found in the cerebral hemispheres in cingulate, auditory and visual association cortices and the brain stem. Altogether, these findings suggest that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control, rather than in primary vessel diameter changes.

English Abstract↗
PubMed1996

Characterization of the sialic acid-binding site in sialoadhesin by site-directed mutagenesis.

The sialoadhesins are a distinct subgroup of the immunoglobulin superfamily, comprising sialoadhesin, CD22, the myelin-associated glycoprotein, and CD33. They can all mediate sialic acid-dependent binding to cells with distinct specificities. Sialoadhesin is a murine macrophage-restricted cell-surface molecule with 17 extracellular immunoglobulin-like domains that recognizes NeuAc alpha 2-3Gal in N- and O-glycans and interacts preferentially with cells of the granulocytic lineage. Its sialic acid-binding site is located within the NH2-terminal (membrane-distal) V-set domain. Here we have carried out site-directed mutagenesis in an attempt to identify the binding site of sialoadhesin. A subset of nonconservative mutations disrupted sialic acid-dependent binding without affecting binding of three monoclonal antibodies directed to two distinct epitopes of sialoadhesin. A CD8 alpha-based molecular model predicts that these residues form a contiguous binding site on the GFCC'C" beta-sheet of the V-set domain centered around an arginine in the F strand. A conservative mutation of this arginine to lysine also abolished binding. This amino acid is conserved among all members of the sialoadhesin family and is therefore likely to be a key residue in mediating sialic acid-dependent binding of sialoadhesins to cells.

Amino Acid Sequence↗
PubMed1996

[Technical and clinical success with extracorporeal shockwave lithotripsy in pancreatic duct calculi].

BACKGROUND: Chronic pancreatitis is often complicated by concrements obstructing the main pancreatic duct. Duct obstruction is discussed as potential mechanism responsible for recurrent and persistent pain. PATIENTS AND METHODS: 75 symptomatic patients (15 female, 60 male; 46 +/- 12 years) with stones in the main pancreatic duct (solitary n = 23; multiple n = 52) primarily not endoscopically extractable even after sphincterotomy of the pancreatic orifice were treated by means of a piezoelectric lithotripter (Piezolith 2500). Fragmentation and stone clearance were documented by ERP. The clinical benefit was evaluated in 35 patients (9 female, 26 male; 45 +/- 12 years) followed up meanwhile for more than 12 (29 +/- 14) months. RESULTS: After 3 +/- 2 (1 to 10) ESWL-sessions/patient the concrements were fragmented successfully in 80% of the patients. Focussing of the stones was achieved sonographically (15%), fluoroscopically (45%) or using both imaging techniques (40%). In total, 61% of the patients became stone free, 44% spontaneously, in further 17% all remaining fragments could be removed endoscopically. In 39% of the patients only a partial extraction was achieved. Severe complications due to shockwave application did not occur. The majority of the patients (stonefree n = 22, remaining fragments n = 13) followed up > or = 12 months kept free of pain (51%) or reported on pain relief (26%). Nine patients developed 13 recurrent calculi, which were again treated successfully by interventional measures in 8/9 patients. CONCLUSIONS: The data confirm the value of extracorporeal shockwave lithotripsy as an important tool in the interventional therapy of chronic pancreatitis. Even if recurrent calculi may occur, the majority of patients will experience at least a medium-term profit by those measures due to pain relief.

Adult↗
PubMed1996

2.0 A resolution structure of a ternary complex of pig muscle phosphoglycerate kinase containing 3-phospho-D-glycerate and the nucleotide Mn adenylylimidodiphosphate.

The crystal structure of a ternary complex of pig muscle phosphoglycerate kinase (PGK) containing 3-phosphoglycerate (3-PG) and manganese adenylylimidodiphosphate (Mn AMP-PNP) has been determined and refined at 2.0 A resolution. The complex differs from the true substrate ternary complex only in the presence of an imido- rather than an oxylink between beta- and gamma-phosphates of the bound nucleotide. The 3-PG is bound in a similar manner to that observed in binary complexes. The nucleotide is bound in a similar manner to Mg ADP except that the metal ion is coordinated by all three alpha-, beta-, and gamma-phosphates, but not by the protein. The gamma-phosphate, which is transferred in the reaction, is not bound by the protein. One further characteristic of the ternary complex is that Arg-38 moves to a position where its guanidinium group makes a triple interaction with the N-terminal domain, the C-terminal domain, and the 1-carboxyl group of the bound 3-PG. Although a hinge-bending conformation change is seen in the ternary complex, it is no larger than that observed in the 3-PG binary complex. To reduce that distance between two bound substrates to a value consistent with the direct in-line transfer known to occur in PGK, we modeled the closure of a pronounced cleft in the protein structure situated between the bound substrates. This closure suggested a mechanism of catalysis that involves the "capture" of the gamma-phosphate by Arg-38 and the N-terminus of helix-14, which has a conserved Gly-Gly-Gly phosphate binding motif. We propose that nucleophilic attack by the 1-carboxyl group of the 3-PG on the gamma-phosphorus follows the capture of the gamma-phosphate, leading to a pentacoordinate transition state that may be stabilized by hydrogen bonds donated by the NH groups in the N-terminus of helix 14 and the guanidinium group of Arg-38. During the course of the reaction the metal ion is proposed to migrate to a position coordinating the alpha- and beta-phosphates and the carboxyl group of Asp-374. The mechanism is consistent with the structural information from binary and ternary substrate complexes and much solution data, and gives a major catalytic role to Arg-38, as indicated by site-directed mutagenesis.

Adenylyl Imidodiphosphate↗
PubMed1996

Changes in cerebral blood flow velocity after treatment with sumatriptan or placebo and implications for the pathophysiology of migraine.

Whether the primary mechanisms of migraine are vascular or neurogenic is, as yet, unresolved. In humans it is still unclear whether sumatriptan acts via constriction of dilated arteries or through other mechanisms. Doppler sonography is a non-invasive method for measuring blood flow velocities (BFV), an indirect marker of vessel diameter. This double-blind crossover placebo-controlled trial investigated changes in BFV in extra- and intracranial arteries in 132 migraine attacks (66 patients) before and after treatment with either 6 mg sumatriptan s.c. or placebo. Significant increases in BFV were observed only in the middle cerebral artery (MCA) and the basilar artery (BA) after administration of sumatriptan. However, the majority of the patients showed no change in BFV following sumatriptan. No difference in BFV could be detected between headache and non-headache side or between migraine and headache free periods. Despite a slight increase in BFV in intracerebral arteries, this study does not support the concept that vasoconstriction is sumatriptan's principal mechanism in pain relief.

Adult↗
PubMed1996

Endothelin antagonist bosentan blocks neurogenic inflammation, but is not effective in aborting migraine attacks.

Bosentan, a specific mixed antagonist of endothelin receptors with no vasoconstrictor activity, inhibits neurogenic plasma extravasation (NPE) within rat dura mater. This would predict efficacy in aborting migraine attacks, without causing cardiovascular side-effects. We investigated the efficacy of 250 mg i.v. bosentan in a randomized, double-blind, placebo-controlled, clinical trial. Improvement from moderate/severe to mild/no headache at 2 h (primary efficacy measure) occurred in 5/23 (22%) of bosentan-treated and in 9/25 (36%) of placebo-treated patients (effect difference -14%; 95% CI -52%, 24%). Thus, inhibition of NPE may not predict clinical efficacy of experimental antimigraine drugs. Vasoconstrictor action may be needed.

Adult↗
PubMed1996

Prospective evaluation of hemostatic predictors of subacute stent thrombosis after coronary Palmaz-Schatz stenting.

OBJECTIVES: This study sought to investigate hemostatic predictors of subacute occlusive coronary stent thrombosis. BACKGROUND: Better hemostatic monitoring may improve antithrombotic therapy after stenting. METHODS: In 140 consecutive patients undergoing Palmaz-Schatz stent implantation for suboptimal angioplasty results, we obtained serial blood samples immediately before and daily for 12 days after stenting. We prospectively tested the hypothesis that subacute stent thrombosis was more frequent if the surface expression of the inducible fibrinogen receptor on platelets (flow cytometry) or the concentration of plasma fibrinogen or that of the prothrombin fragments F1 + 2 before stent implantation exceeded the 75th percentile of the entire study cohort. RESULTS: All five stent occlusions encountered during the study occurred in patients with platelet fibrinogen receptor expression above the 75th percentile. Thus, the rate of stent occlusion differed significantly between the groups defined by platelet fibrinogen receptor expression (14.3% vs. 0%, p = 0.0008). In both the group with fibrinogen concentration and that with F1 + 2 concentration above the 75th percentile, three stent occlusions occurred. Between the groups defined by these variables, the rate of stent occlusion did not differ significantly (8.6% vs. 1.9%, p = 0.10). Logistic regression analysis, including angiographic and hemostatic variables, confirmed platelet fibrinogen receptor expression as an independent predictor of stent occlusion (p = 0.020). Stent occlusion could not be predicted by the time course of any of the hemostatic variables. CONCLUSIONS: Platelet fibrinogen receptor expression is an independent predictor of subacute stent occlusion. However, fibrinogen and F1 + 2 concentrations do not show a strong relation to the risk of stent occlusion.

Adult↗
PubMed1996

Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system?

A series of studies demonstrated a possible correlation between eye-blink rate and central dopamine activity. The hypothesis has been put forward that the antidepressant effect of sleep deprivation (SD) is mediated by an enhanced dopamine release resulting in an amphetaminelike action of SD. Therefore, the blink rates of 12 drug-naive patients with major depression and 12 healthy controls were compared before and after SD and before and after 2.5 mg bromocriptine as a dopaminergic challenge. The main result of the study was that the depressed patients had a significantly higher increase of blinking after SD both with and without a dopaminergic challenge. Basal eye-blink rate was not different in nonretarded major depression patients compared to controls. Sleep deprivation increased blink rate in depression patients but not in controls, and the increase was proportional to improvements in depressive state after sleep deprivation. Bromocriptine did not increase blink rate 1 hour after application. This result is consistent with the hypothesis that antidepressant SD acts through dopamine release, although it is not conclusive, because other neurotransmitters like acetylcholine may be involved in the regulation of blinking.

Adult↗
PubMed1996

Sumatriptan: vasoactive effect on human dural vessels, demonstrated by subselective angiography.

Sumatriptan, a selective 5-hydroxytryptamine (5HT1D)-receptor agonist, has recently been introduced in the pharmacotherapy of acute migrane attacks. The potential vasoactive effect of sumatriptan on human dural vessels in vivo, however, is still a matter of controversy. We investigated the effects of sumatriptan on dural vessels after subcutaneous or intra-arterial injection. During interventional angiography, the middle meningeal artery (MMA) of nine patients was catheterized with a microcatheter using the transfemoral route. Three MMA were entirely normal, two supplied a dural arteriovenous fistula (AVF) and four were transdural feeders to a brain arteriovenous malformation (AVM). Sumatriptan was injected either into the subcutaneous tissue of the right shoulder (6 mg, two patients) or into the catheterized MMA (2 mg, six patients). The substance caused a marked vasoconstriction of the three normal MMA, visible angiographically and confirmed by intravascular Doppler ultrasonography. Vasoconstriction was still present in the last angiogram obtained 15 min post-injection. Slightly hypertrophied feeders to dural AVF and to brain AVM showed some vasoconstriction in one and four patients, respectively. In two patients with markedly hypertrophied dural feeders to a dural AVF and to a brain AVM, respectively, rapid shunting probably prevented obvious vasoactive effects of sumatriptan. The data obtained by angiography and intravascular Doppler ultrasonography provide strong evidence that sumatriptan has a vasoconstrictive effect on normal as well as hypertrophied dural vessels.

Adult↗
PubMed1996

Self-expanding metal stents for palliation of malignant obstruction in the upper gastrointestinal tract. Comparative assessment of three stent types implemented in 96 implantations.

Self-expanding metal stents provide a new option for the palliative treatment of malignant stenoses from tumors of the esophagus. Our present study provides a comparative assessment of clinical experience gained consecutively in the implementation of three stent versions in a total of 87 patients and 96 implantations. Thirty-one Wallstents (Scheider, Lusanne, Switzerland) (five coated) were implanted in 23 patients, 35 Ultraflex stents (Boston Scientific, Boston, MA, U.S.A.) (uncoated) in another 34 patients, and 30 Gianturco-Z stents (Cook, Winston-Salem, NC, U.S.A.) (all coated) in a group of 30 patients. In the three patient groups there were no significant differences as to the degree of dysphagia, number of pretreatments, length of the tumor stenosis, tumor location, or histological classification. Seven patients who had been treated with Gianturco-Z stents presented with an esophagorespiratory fistula. Technically, all 96 implantation procedures were successful. Complete sealing of the fistulas was verified by radiography in all patients who had developed fistulas. Severe early complications in the form of stent migration were encountered in only three of 96 implantations (3%). Within the early period after stent placement in five patients of the Wallstent group (22%), 13 patients of the Ultraflex group (37%), and three patients of the Gianturco group (10%), retreatments were necessary due to stent dislocation and/or insufficient stent expansion. The degree of dysphagia improved distinctly and with a comparable development in all three patient groups. The rate of reintervention (percentage of patients) due to major and minor problems in the follow-up period amounted to 43% (Wallstents), 35% (Ultraflex stents), and 21% (Gianturco-Z stents). In view of the low number of complications (3%) in the early stage of implantation, self-expanding metal stents provide an improved approach for palliative therapy of malignant stenoses of the esophagus. Nevertheless, further technological improvements are necessary to reduce the great frequency of unavoidable reinterventions (20-43%) in the follow-up period.

Adult↗
PubMed1996

New aspects of migraine pathophysiology: lessons learned from positron emission tomography.

Recent positron emission tomography investigations found spreading oligemia in the early phases of a human migraine attack. During the headache phase, increased cerebral blood flow was found in cortical sensory association areas and unilaterally in the brainstem. The brainstem activation persisted after complete relief from headache, indicating that this area might reflect the 'migraine generator'.

Brain Stem↗
PubMed1996

The molecular basis of the sideroblastic anemias.

The sideroblastic anemias display remarkable clinical and hematologic heterogeneity but share in common mitochondrial iron loading as evidence of unhinging between intracellular iron metabolism and heme biosynthesis. Molecular defects responsible for this unhinging have now been identified and appear to display matching heterogeneity. Mutations in the erythroid-specific ALA synthase 2 (ALAS2) gene cause microcytic anemia, whereas mitochondrial DNA deletions are responsible for Pearsons syndrome with a macrocytic anemia. The molecular basis for other causes including X-linked non-ALAS2-associated autosomal inheritance and for the more frequent acquired forms of this disorder awaits discovery. Speculation about their causes includes disturbed intracellular iron homeostasis involving iron-responsive factors involved in the translational control of ALAS2 and in certain nuclear and mitochondrial genes important for erythroid mitochondrial metabolism.

5-Aminolevulinate Synthetase↗
PubMed1996

Changes in membrane glycoproteins of circulating platelets after coronary stent implantation.

OBJECTIVES: To evaluate platelet function in patients with coronary stents. DESIGN: A non-randomised control trial in 30 patients who had immediate implantation of Palmaz-Schatz coronary stents because of a suboptimal angioplasty result. All patients received a standardised anticoagulation regimen including intravenous heparin (activated partial thromboplastin time (APTT) 80 to 120 s), oral vitamin K antagonist (target international normalised ratio (INR) of 3.5), and 100 mg aspirin twice daily. Platelet surface expression of glycoprotein IIb-IIIa, activated fibrinogen receptor, and P-selectin as well as binding of von Willebrand factor and fibrinogen were determined by flow cytometry in peripheral venous blood samples collected before the intervention and then daily for 4 days after it. The results were compared with those in 30 patients undergoing elective coronary balloon angioplasty. SETTING: University hospital. RESULTS: After coronary stenting surface expression of the activated fibrinogen receptor significantly increased, peaking at day 2 (P < 0.001). Similar results were found for von Willebrand factor binding and P-selectin surface expression, with a maximum at day 2 to 4 after stenting (von Willebrand factor, P < 0.001; P-selectin, P < 0.001). The changes in platelet membrane glycoproteins coincided with a significant drop in peripheral platelet count after stent placement (P < 0.01). No significant change in fibrinogen receptor activity, von Willebrand factor binding, P-selectin surface expression, or platelet count was seen in the control group. CONCLUSIONS: The present study shows that current anticoagulation treatment is inefficient in suppressing platelet activation in patients with coronary stents and, therefore, might not be the best treatment for reducing the incidence of subacute stent thrombosis.

Adult↗
PubMed1996

Mitochondrial DNA in migraine with aura.

Migraine and the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have some clinical features in common. First, cerebral infarctions, most often in the posterior cerebral regions, which are a main symptom of MELAS, may complicate migraine. Second, migrainous headache with vomiting is also a characteristic feature of the MELAS syndrome. Less frequently, hemicranial headache is present in another mitochondrial disease, myoclonic epilepsy with ragged-red fibers (MERRF). Moreover, there is a mild bias toward maternal transmission in migraine. Apart from clinical resemblance, there is some experimental evidence for mitochondrial dysfunction in migraine. There may be depression of respiratory chain enzyme activity in muscle and platelets, and magnetic resonance spectroscopy has revealed a defective energy metabolism in brain and muscle of migraine patients. There has not been a systematic study of mitochondrial DNA in migraine, however. We therefore analyzed the mitochondrial DNA in lymphocytes of 23 migraine patients with aura. Southern blot and polymerase chain reaction analysis of mitochondrial DNA failed to detect any large-scale deletions or point mutations at base pair 3243 (MELAS) and base pair 8344 (MERRF). Our data show that deletions of mitochondrial DNA and the most frequent point mutations of MELAS and MERRF syndromes are not common in migraine with aura. In particular, these data do not support the hypothesis that some cases of migraine may be monosymptomatic forms of a MELAS syndrome. We cannot exclude, however, that migraine may be associated with different point mutations of mitochondrial DNA or with mutations of autosomally coded respiratory chain subunit genes.

Adolescent↗
PubMed1995

[Self-expanding metal endoprosthesis in palliation of stenosing tumors of the upper gastrointestinal tract. Comparison of experience with three stent types in 82 implantations].

INTRODUCTION AND AIM OF STUDY: As there are no reports of studies comparing different self-expanding metal stent types the results obtained with three stent types in 73 patients (58 men, 15 women; mean age 65 [43-90] years who had a total of 82 implantation were analysed. PATIENTS AND METHODS: 31 Wallstents were implanted in 23 patients, 31 Ultraflex stents (all without covering) in 30 patients, and 20 Gianturco-Z stents (with covering) in 20 patients. The three groups of patients did not differ significantly with respect to degree of dysphagia, frequency of previous treatment, length of stenosis by tumour, tumour localization and histological tumour type. Six patients, treated with the Gianturco-Z stent, had an tracheo-oesophageal fistula. RESULTS: All 82 implantations were technically successful. Complete occlusion was achieved in all patients with fistulas, as proven radiologically. Serious early complications, namely stent migration, occurred in two patients (2.4%). The degree of dysphagia improved equally in all three groups (Wallstent, from 2.0 to 0.7; Ultraflex from 2.2 to 0.9, Gianturco-Z from 2.1 to 0.5 (not significant). The median follow-up time differed: 89 days for the Wallstent group, 129 for the Ultraflex group and 77 days for the Gianturco-Z group. Tumour ingrowth was the main problem with the non-covered stents. Accordingly, there were 43% reinterventions with the Wallstent, 37% with the Ultraflex and 20% with the Gianturco-Z stents. CONCLUSIONS: Self-expanding metal stents improve palliative treatment of stenosing tumours of the oesophagus and cardia, particularly in view of the low complication rate (< 3%) in the early postimplantation phase. But technical improvements are needed to reduce the number of reinterventions for restenosis in the follow-up period.

Adult↗
PubMed1995

DNA repair in the endogenous and episomal amplified c-myc oncogene loci in human tumor cells.

We have studied the repair of u.v.-induced cyclobutane pyrimidine dimers (CPDs) in amplified c-myc oncogene loci in human colon cancer cells to better understand the relationship between chromatin structure, transcription and DNA repair. To assess the variation in DNA repair in the same gene whether located in a chromosomal site or in a extra-chromosomal site, we have quantitated the efficiency of excision repair after u.v. exposure in the endogenous and episomal c-myc genes isolated from COLO320HSR and DM cells. In the HSR cells, c-myc is localized in a homogeneously staining region (HSR), and in the DM cells, the gene is localized in double minute chromosomes (DM). Our results indicate that the repair is less efficient in c-myc amplicons organized as double minute chromosomes than in the endogenous c-myc amplicons. The episomal gene is not repaired with the same efficiency as when it is intrachromosomal. This may reflect differences in chromatin structure. An advantage of this biological system is that the cells possess two different alleles of the c-myc gene, one that is active and another which is inactive. We have studied the relationship between DNA repair and transcriptional activity in the c-myc locus by measuring the efficiency of excision repair after u.v. exposure in the normal and rearranged alleles of the c-myc gene. Surprisingly, the c-myc gene is repaired with similar efficiency in the highly transcribed allele as in the poorly expressed allele. However, u.v. damage is selectively removed from the transcribed strand of the active c-myc allele, but DNA repair is not strand specific in the non-expressed c-myc allele.

Chromosome Mapping↗