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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 397 records · Page 22Linked to original sources

Simple detection of the inter-alpha-trypsin-inhibitor (ITI) polymorphism by isoelectric focusing with direct immunofixation.

The inter-alpha-trypsin inhibitor (ITI) polymorphism was analysed in a German population, using polyacrylamide gel isoelectric focusing with subsequent direct immunofixation with monospecific ITI antisera. Gene frequencies of ITI*1, ITI*2, ITI*3, and ITI*4 were calculated to be 0.6150, 0.3753, 0.0078 and 0.0019, respectively. In our study the allele ITI*4 is described for the first time in a German population.

Alleles↗

The roles of multiple pathways in regulating bombesin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts.

The regulation of bombesin-stimulated phospholipase D (PLD) activity in Swiss 3T3 fibroblasts was examined. Increasing protein-tyrosine phosphorylation by using pervanadate to inhibit tyrosine phosphatases was found to stimulate protein kinase C (PKC)-independent [3H]phosphatidylbutanol ([3H]PtdBut) accumulation within 5 min, which continued to increase up to 30 min. The stimulation of PLD activity in response to submaximal [bombesin] could be decreased by approx. 50% by the tyrosine kinase inhibitor genistein, whereas pretreatment with genistein and the PKC inhibitor Ro-31-8220 completely abolished the generation of [3H]PtdBut in response to a maximal concentration of bombesin. The addition of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) into permeabilized cells resulted in an increase in [3H]PtdBut, which was abolished by depletion of cellular ATP. The additional presence of 30 microM GTP[S] did not increase the stimulation of PLD activity by any [bombesin] tested, whereas it was synergistic with that stimulated in response to phorbol 12-myristate 13-acetate. These findings suggest that bombesin-stimulated PLD activity is indirectly regulated by G-proteins, possibly through a kinase intermediate. Furthermore, activation of protein tyrosine kinases is proposed to account for the PKC-independent arm of bombesin-stimulated PLD activity. No evidence was obtained for a form of PLD directly regulated by tyrosine phosphorylation.

3T3 Cells↗

Purification and characterization of the N-terminal domain of galectin-4 from rat small intestine.

Using affinity chromatography on lactose-agarose, five beta-galactoside binding lectins of 14 to 20 kDa were detected in the rat small intestinal mucosa. The prominant proteins of 17 and 19 kDa were purified to homogeneity by 2D-electrophoresis. Direct N-terminal sequencing of the 17 kDa protein and intrachain sequencing of the 19 kDa protein produced sequences which are part of the N-terminal domain of the L-36/galectin-4. A rabbit polyclonal antibody was raised against the 19 kDa lectin, which specifically recognized the 17 and 19 kDa lectins and detected a related 36 kDa protein in human undifferentiated HT29 cells.

Amino Acid Sequence↗

Motor function in a patient with bilateral lesions of the globus pallidus.

This study describes the long-term deficits of a patient who, after a toxic encephalopathy, sustained extensive bilateral damage to both segments of the globus pallidus (GP) and the right substantia nigra (SN). There were no signs of lesions of the pyramidal tracts or of other motor structures. The most obvious deficits were an abnormal gait with an exaggerated knee extension and a tendency to fall slowly, especially when pushed backward. In contrast, Romberg's test on an unstable platform was normal, as were long-latency leg reflexes induced by perturbations. Inadequate anticipatory and compensatory postural responses, in particular across the hip and knee joints, and slow movements seemed responsible for the falls. Muscle tone was normal but reflex studies showed signs of abnormal facilitation and inhibition at various levels of the neuraxis. We conclude that the GP and SN lesions caused defective input to premotor cortical and brain stem target zones. Dysfunctioning of these zones leads to improper control of the descending ventromedial motor system responsible for locomotion, postural control, and reflex status. The deficits in upper extremity motor performance included delayed and slow movements, inaccurate amplitudes of ballistic responses, a lack of predictive control, and deficits in bimanual coordination. Sensory feedback, proprioceptive more than visual, played a powerful compensating role in rapid aiming movements. Regional blood flow (studied using 15(O)2) was reduced in multiple frontal cortical regions, among which are the hand areas of the supplementary and premotor cortex. We hypothesize that this reflected impaired functioning of these areas, caused by defective bilateral output from GP and SN, and resulting in the motor deficits of the arm and hand.

Adult↗

Cloning and molecular analysis of the Isi1 (rfaF) gene of Neisseria meningitidis which encodes a heptosyl-2-transferase involved in LPS biosynthesis: evaluation of surface exposed carbohydrates in LPS mediated toxicity for human endothelial cells.

Neisseria meningitidis, but not Haemophilus influenzae, damage cultured human endothelial cells. We have undertaken a study to generate genetically and structurally defined lipopolysaccharide (LPS) mutant strains of meningococci for functional studies to assess the role of surface exposed oligosaccharides in imparting specificity of toxic damage to human endothelial cells. The Isi1 gene, which had been shown to be involved in LPS biosynthesis of Neisseria gonorrhoeae, was amplified by PCR and cloned. Nucleotide sequence analysis confirmed the identity of the clone and revealed homology with Isi1 of N. gonorrhoeae and the rfaF gene of Salmonella typhimurium which encodes a heptosyl-2-transferase involved in LPS biosynthesis. The identity of the cloned Isi1 gene, as a functional rfaF homologue, was confirmed by the complementation of a S. typhimurium rfaF mutant using a P22 phage sensitivity test. An Isi1 mutant meningococcal strain was constructed, and structural analysis of the mutant LPS molecule revealed a single heptose in the core structure, consistent with a heptosyl-2-transferase deficient mutant. In order to investigate the relative cytotoxicities of meningococci expressing native and altered LPS, wild type, Isi1, and galE strains were compared in cytotoxicity assays using human umbilical vein endothelial cells (Huvecs) in culture. Analysis using Huvecs derived from several individuals (cords) showed that the three phenotypes were almost equally cytotoxic. Removal of the terminal portion (galE mutant) or the majority (Isi mutant) of the oligosaccharide did not effect LPS-mediated cytopathic damage to Huvecs in a culture suggesting that the oligosaccharide portion did not play a major role in cytotoxicity.

Amino Acid Sequence↗

Calcitriol effect on natural killer cells from hemodialyzed and normal subjects.

Patients with chronic renal failure have a decreased secretion of calcitriol (CTR). They also show an impaired cellular immune response including a defective natural killer (NK) cell-mediated activity. The aim of this study was to analyze, in vivo and in vitro, the effect of CTR on NK cell cytotoxicity in healthy control subjects and in hemodialyzed (HD) patients. Our results show that HD patients had baseline-depressed NK cell activity when compared with controls (P < 0.001), which increased significantly after 1 month of oral CTR treatment (0.5 microgram/day) (P < 0.001). Calcitriol treatment also induced a significant increase in CTR serum levels (P < 0.001) and a significant decrease (P < 0.001) in total parathyroid hormone (PTH). In vitro CTR treatment (10(-7) M) of peripheral blood mononuclear cells (PBMC) increased NK cell-mediated cytotoxicity after 24 hours of incubation with a maximum at 48 hours (P < 0.001). In vitro CTR treatment at doses of 10(-11) and 10(-9) M did not significantly increase NK cytotoxic activity. The enhanced NK activity after CTR treatment was not the consequence of increased numbers of CD56 positive cells, nor to lymphocyte activation, as tested by the expression of the interleukin 2 receptor p55 alpha chain (CD25) on their surface. In vitro treatment of PBMC from HD patients with CTR (10(-7) M, during 48 hours) also induced a strong increase in NK cell cytotoxicity (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment.

Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Changes induced by eccentric training on force-velocity relationships of the elbow flexor muscles.

The aim of this study was to examine the effects of a short term eccentric training period on force-velocity relationships of the elbow flexor muscles. From a muscle model, the maximal shortening velocity Vo(x) and the af parameter which varies according to the curvature of the force-velocity relationship of the muscle were determined. Sixteen volunteer subjects divided into 2 groups participated in this study (Group Eccentric GE, n = 8; Group Control GC, n = 8). The subjects performed, on an isokinetic ergometer, 2 maximal concentric elbow flexions at different angular velocities (60, 120, 180, 240, 300, 360 degrees s-1) and held maximal and submaximal isometric actions at an elbow flexion angle of 90 degrees. Under isometric conditions, myoelectrical activity (EMG) of the biceps was recorded and quantified as a RMS value. All tests were performed before and after training sessions. Training was conducted 3 times a week for 4 weeks by the GE, and included 6 x 5 eccentric actions with a load of 100% of 1 RM. After training and for the GE, the af parameter and Vo(x) increased significantly (p < 0.05). These changes were accompanied by a significant increase (p < 0.05) of the RMS value of the maximal isometric action. This evolution towards faster characteristics for the elbow flexor muscles after training could be partly due to nervous adaptation.

Elbow↗

Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans.

Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonist m-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine+ondansetron, and scopolamine+m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.

Aged↗

Effect of dietary fiber at weaning on protein glycosylation in the rat small intestine.

Changes in protein glycosylation which can be modulated by dietary factors are observed in the rat intestinal mucosa at the weaning period. Experiments were performed to evaluate the involvement of dietary fibers in the regulation of such modifications. Groups of rats were abruptly weaned at 19 days of age on semi-synthetic diets differing in dietary fiber content (fiber-free, 10% pectin or 10% cellulose) given for 4 and 10 days. Glycoprotein sugars, activities of the fucosylation pathway and caecal contents were analyzed. Neutral sugar contents in glycoproteins of the small intestinal mucosa were increased in teh fiber-fed groups as compared to fiber-free group, only after 4 days but not after 10 days of diet. Diet-induced modifications in the glycoprotein fucose content of the small intestinal mucosa are partly explained by the coordinated evolution of different activities involved in the fucosylation pathway (GDP-fucose production and breakdown, fucosyltransferase and fucosyltransferase inhibitor). Caecal contents of short chain fatty acids were significantly different between the three groups after 4 but not after 10 days of diet. There was no correlation between caecal short chain fatty acid contents and activities involved in the fucosylation pathway. The introduction of dietary fibers at weaning induced marked but transient changes in glycoprotein sugars and the fucosylation pathway. The results demonstrate that fucosylation is regulated in several ways including changes in fucosyltransferase activity but that caecal fermentation of dietary fibers was not directly responsible for the observed changes.

Animals↗

Santolindiacetylene, a polyacetylene derivative isolated from the essential oil of Santolina canescens.

The yield, composition, and some pharmacological activities (hepatoprotective and antioxidant) of the essential oil of Santolina canescens aerial parts have been investigated. The essential oil qualitative data were determined by gc and gc-ms. The main component, santolindiacetylene [1], was isolated and characterized by spectral methods, and the structure assigned as 1-(2'-naphthyl)hexa-2,4-diyne. The protective activities of the essential oil and its main component [1] were evaluated against carbon tetrachloride-induced hepatotoxicity in a rat model. In both cases a significant hepatoprotective effect was observed, as evident from the strong decrease of elevated GPT serum levels caused by carbon tetrachloride-induced hepatic damage.

Alkynes↗

Effects of specific dietary sugars on the incorporation of 13C label from dietary glucose into neutral sugars of rat intestine and serum glycoproteins.

Although theoretically all glycoprotein sugars can be derived from glucose, it may be hypothesized that specific dietary sugars could be preferential substrates for glycoprotein synthesis. To test this hypothesis, groups of rats received either continuously (continuous-labelling experiment) or for a single nutritional period (pulse-labelling experiment) a 13C-rich diet containing either maize starch or artificially labelled [13C]glucose. Some groups of rats were also provided during a single nutritional period with low amounts (20-200 mg/animal) of low-13C dietary sugars (mannose, galactose, fucose or fructose). If specific dietary sugars were preferentially incorporated into glycoproteins instead of glucose-derived labelled sugars, a decrease would be expected in the intestinal or serum glycoprotein-sugar 13C enrichment monitored by gas chromatography-isotope-ratio mass spectrometry (GC-IRMS). Contrary to this hypothesis the results showed no significant decrease with any of the specific dietary sugars. Furthermore, with dietary low-13C mannose or galactose, a significant increase in 13C enrichment of glycoprotein-sugars was observed compared with some other nutritional groups. Moreover, in the pulse-labelling experiment, dietary mannose and galactose induced similar patterns of 13C enrichment in intestinal and serum glycoprotein-sugars. Therefore, although specific dietary sugars do not appear to be preferential substrates for glycosylation under conditions and doses relevant to current concepts of nutrition, regulatory roles of some specific dietary sugars in relation to glycoprotein-sugar metabolism might be hypothesized. These findings could lead to similar studies using stable-isotope methodology in man which could have practical consequences, especially in parenteral nutrition where glucose is the only sugar provided to the metabolism.

Animals↗

Working memory as assessed by subject-ordered tasks in patients with obsessive-compulsive disorder.

We tested patients with obsessive-compulsive disorder (OCD) and normal subjects (n = 18 per group) on a self-paced, working memory task that, based on studies of patients with focal brain lesions and functional brain imaging studies of normals, is largely mediated by prefrontal cortex. The OCD patients had normal working memory spans and normal recognition memory for all types of material tested (abstract words, common objects, and novel nonsense objects). The patients, however, were slow (p < .005), and the time they took to complete the tasks was significantly correlated with ratings of OCD symptoms (r = .539, p < .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on this self-paced task was discussed in relation to normal response times by OCD patients under typical laboratory conditions. It was suggested that this discrepancy may be related to a broader dissociation between real-world and laboratory performance as seen in some patients with prefrontal lobe dysfunction.

Adult↗

Reaction time slowing in HIV-1-infected individuals: role of the preparatory interval.

Psychomotor speed and directed attention were evaluated in 83 human immunodeficiency virus-1-infected individuals (HIV+) and 50 HIV-1 seronegative (HIV-) control participants using simple and choice reaction time (RT) tasks. The simple RT task included 1- and 3-s, irregularly varied preparatory intervals (PI) between the warning and target lights. Relative to the HIV- group, simple and choice RT were significantly slowed in the HIV+ group. Further, again relative to the HIV- controls, the HIV+ group did not show expected faster RT with increased response preparation time in the simple RT task. This also occurred in some HIV+ subjects who did not have psychomotor slowing. These findings suggest that RT performance in HIV-1-infected individuals may reflect separate processes associated with psychomotor slowing and impaired ability to direct attention. Possible neural mechanisms associated with control of these processes are discussed.

Acquired Immunodeficiency Syndrome↗

Epitope studies indicate that histidyl-tRNA synthetase is a stimulating antigen in idiopathic myositis.

The most frequently found myositis-specific antibody, the anti-Jo-1 antibody (anti-HRS), binds to histidyl-tRNA synthetase (HRS). Although this antibody reacts with HRS, it is unclear whether HRS is the stimulating antigen or is merely a protein that cross-reacts with a yet undefined antigen. Because antibody directed against an unrelated antigen would not be expected to cross-react with HRS at multiple sites, we mapped the epitopes on HRS to resolve this issue. We found by Western blot analyses that immunoglobulins G (IgG) from 18 of 19 anti-HRS positive patient sera react with amino acids 2-44 and 286-509 of HRS. Patient IgG specific for these two epitopes were found not to inhibit HRS enzyme activity. Instead, the inhibitory property of anti-HRS was found to be associated with antibodies that do not react to HRS in immunoblots, indicating the presence of other epitopes. In addition, antibodies that react in immunoblots were found to represent only a small fraction of total anti-HRS antibody. Our finding that patient IgG recognized at least three distinct epitopes on HRS strongly suggests that the immunological response at some point in the disease is directed against HRS and not against a cross-reactive antigen.

Epitope Mapping↗