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Biomedical subjects

W Lang

Publications and source records attributed to W Lang.

At least 145 records · Page 8Linked to original sources
PubMed1997

Curdlan sulfate (CRDS) in a 21-day intravenous tolerance study in human immunodeficiency virus (HIV) and cytomegalovirus (CMV) infected patients: indication of anti-CMV activity with low toxicity.

This study evaluated tolerance (and possible efficacy) for 21 days of i.v. administration at three dose levels of curdlan sulfate (CRDS) (a semisynthetic sulfated polysaccharide), administered over 30 minutes, in HIV and CMV (in some cases) infected individuals with CD4 levels < 500 cells/mm3. Half of the subjects were previously treated with reverse transcriptase inhibitors (RTI) (which were continued during the CRDS administration) and half the patients had no prior RTI treatment. Evaluation of other sulfated polysaccharides in HIV had been discontinued due to side effects and lack of activity. Three groups of HIV patients (also including subsets with CMV infection) were treated separately with 50 mg/70 Kg, 100 mg/70 Kg and 200 mg/70 Kg of CRDS infused i.v. over thirty minutes daily for 21 days. In each dose group, half of the patients selected were being treated with a RTI and half were on no RTI. Patients were monitored for CD4 cell levels, viral load in some cases, and safety parameters in blood. Samples of urine and semen were additionally taken for CMV by culture and for PCR assay in subsets of participants. CRDS in this 21 day study was well-tolerated and produced few reportable side effects. Systematic decreases in platelets and increases in p24 antigen previously seen with dextran sulfate were not observed in this study with CRDS. In the 21 patients testing positive for CMV at the start of the study, 12 were CMV negative at the end of 21 days. In an untreated historical control group, 0/36 went from CMV positive to negative over a period of 13-15 years. The anti-CMV activity of CRDS in this study, therefore, had a p value < 0.001, based on these historical controls. The marked temporary increases in CD4 levels seen in the single dose and the seven-day CRDS studies on HIV patients were also seen for 21 days in the current study (p = 0.0001). Treatment with CRDS seems promising against CMV in HIV infected patients, even with once daily dosing of this two-hour half-life drug. CRDS was well tolerated and its lack of toxicity makes it an attractive candidate for CMV-infected HIV patients. Multiple daily dosing, or the continuous infusion of CRDS, could lead to increased effectiveness against both HIV and CMV, especially in combination with other agents. Given the toxicity of existing anti-CMV agents, and considering the emerging importance of CMV in atherosclerotic disease, further studies on CRDS are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1996

High-performance liquid chromatographic determination of anandamide amidase activity in rat brain microsomes.

A rapid, sensitive, and reliable method for measuring anandamide amidase activity in rat brain microsomes by reversed-phase high-performance liquid chromatography (RP-HPLC) and its applications are described. Enzymatic activity was assayed by the determination of the rates of hydrolysis of anandamide or its analogs at 37 degrees C. The reaction products were separated using an ODS guard column eluted with aqueous phosphoric acid-acetonitrile and quantitated with uv detection at 204 nm and an external standard method. Baseline separation of the acid products from their substrates was completed in less than 2 min. The detection limits were 1.4 pmol for arachidonic acid and 0.22 pmol for anandamide at a signal to noise ratio of 4:1. The stability of anandamide in the acidic mobile phase was tested, and no significant decomposition was observed up to 1 h. The method was successfully applied to the examination of substrate specificity as well as for testing the ability of amidase inhibitors to block its hydrolysis. Kinetic constants obtained for (S)-methanandamide were an apparent Km of 8.6 +/- 1.3 microM and a Vmax of 362 +/- 16 pmol/min/mg of protein. A highly potent inhibitor, palmitylsulfonyl fluoride (PSF), was found to have an IC50 of 50 nM. PSF is 210 times as potent as phenylmethylsulfonyl fluoride. The method offers several advantages over existing methodology using radioisotopes or a solvent extraction procedure.

Amidohydrolases↗
PubMed1996

Electric and magnetic fields of the brain accompanying internal simulation of movement.

Methods of functional brain imaging have been used to identify brain structures which are active during internal simulation of movements (ISM). Between 1977 and 1993 it was consistently reported that the primary motor cortex (MI) is not active during ISM whereas other cortical areas, in particular the supplementary motor area (SMA) are active. ISM was assumed to be a situation of "internal programming'. Brain systems involved in ISM or 'programming' were hypothesized to be superior to and separable from 'executive system' including MI. We have studied electric and magnetic fields of the brain when subjects internally simulated either a single movement or a sequence of movements. Results of the studies are consistent with the assumption that MI is active with ISM. Internally subjects experienced effort which was required to inhibit overt movements during ISM. A recent EEG study showed different patterns of cortical activity with ISM and with movement inhibition suggesting that different brain structures may be active during ISM and movement inhibition [23].

Brain↗
PubMed1996

Supplementary motor area in spatial coordination of bilateral movements: a new aspect to 'the SMA debate'?

To test whether the supplementary motor area's (SMA) role is confined to determining the 'temporal' but not the 'spatial' properties of a movement (H.H. Kornhuber et al., in: W.A. Hershberger (Ed.), Volitional Action, Elsevier, Amsterdam, 1989, pp. 107-168), movement-related scalp-recorded negative DC potential shifts were recorded in bilateral movements requiring complex spatial coordination. In such bilateral continuous rotation movements, the effect of the rotation sense (symmetrical vs. antisymmetrical), i.e. the direction in which an arm or a finger rotated in relation to the other, heavily affected DC shifts over the frontocentral midline. Antisymmetrical rotation of upper limb segments was associated with higher negative DC shifts than symmetrical rotation was. This was true for rotations in the sagittal plane, irrespective of whether the rotation involved predominantly proximal muscles (by a rotation predominantly in the shoulder) or only distal muscles (by a rotation in the metacarpo-phalangeal joint of the index finger). If these negative cortical DC-shifts over the frontocentral midline relate to activity of mesial frontocentral structures including the SMA, then the present results suggest that there is a role for these cerebral areas in spatial coordination of bilateral movements. Surprisingly, this was not the case for similar finger movements performed in the frontal plane. The results of the present study and particularly the considering of some fundamentals of theoretical physics and of Popper's philosophy of science, made us revise our assumption motivating the present study, that time and space would represent two orthogonal factors of a movement and that the contributions of a particular cerebral motor area (such as the SMA) to 'spatial parameters' versus 'temporal parameters' of a movement can thus be teased apart.

Adult↗
PubMed1996

Brain potentials with old/new distinction of non-words and geometric figures.

Event-related potentials (ERPs) were recorded in a continuous memory recognition task. Readable non-words and abstract geometric figures were presented in an alternating manner with an inter-stimulus interval of 2.1 s. Probability of item repetition was 0.25, a lag of one item lay between initial presentation and repetition. OLD/NEW distinction was indicated by the subject's motor response. Using linked-mastoid electrodes for reference, material-specific hemispheric asymmetries of ERPs started 150 ms after stimulus onset in temporo-lateral and parietal recordings with ERPs elicited by non-words being lateralized to the left and those by figures to the right. Clear OLD/NEW ERP effects were found with non-words: Starting about 200-250 ms after stimulus presentation, ERPs of formerly presented (OLD) items were more positive-going in recordings over the midline than ERPs of items that were new and to be repeated (NEW). In contrast, no local OLD/NEW ERP-difference was found with figures. In some brain regions, OLD/NEW ERP-differences were larger over the left hemisphere compared to the right. This finding, however, did not differ between non-words and figures.

Adult↗
PubMed1996

Relationship between weight loss maintenance and changes in serum leptin levels.

Serum leptin concentrations are higher in obese humans than in lean and are decreased by initial weight loss. This study examined the effects of maintenance of weight loss on leptin concentrations and tested whether leptin concentrations at baseline or after initial weight loss are related to the ability to maintain a reduced body weight. Fifty-two overweight women [body mass index (kg/m2) averaging 31.3] were studied before and after a 4 month weight loss program and at 6 month follow-up. Subjects lost 8.1 kg over the 4 month program, and leptin concentrations decreased from 30.1 to 20.4 ng/ml. Initial leptin level per unit body mass index (r = -0.61, p < 0.0001) and weight loss during months 0 to 4 (r = 0.39, p = 0.004) were both significantly associated with initial changes in leptin, and together explained 60% of the variance in change in leptin. Subjects who maintained their weight losses over the 6-month follow-up maintained their reductions in leptin levels; again, weight changes during follow-up were correlated with changes in serum leptin levels (r = 0.41, p = 0.003). There was no evidence that baseline leptin concentration (or leptin/body mass index) or the changes in leptin which accompanied initial weight loss were predictive of subsequent weight regain. Thus, changes in leptin concentration during weight loss track with changes in weight. However, neither baseline concentrations nor initial changes in leptin predict success at weight loss or maintenance.

Adult↗
PubMed1996

Thrombosis of the terminal aorta, deep vein thrombosis, recurrent fetal loss, and antiphospholipid antibodies. Case report.

The antiphospholipid syndrome (APS) consists clinically of both arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia associated with antiphospholipid antibodies (aPL). Most of these patients were initially found to suffer from systemic lupus erythematosus (SLE). There is an increasing group of patients who exhibit antiphospholipid antibodies and thrombotic complications without clinical features of SLE or related autoimmune disease termed primary antiphospholipid syndrome (PAPS). The case of a 29-year-old woman with thrombosis of the terminal aorta and deep vein thrombosis, recurrent fetal loss, antiphospholipid antibodies and serological support for an underlying connective tissue disease, probably preclinical SLE is reported.

Abortion, Habitual↗
PubMed1996

Increase in Ca2+ channel expression by deletions at the amino terminus of the cardiac alpha 1C subunit.

The alpha 1 subunit of the cardiac L-type Ca2+ channel (alpha 1C) is one of the many alternatively spliced products of a single gene that is expressed in a number of excitable tissues. Sequence comparison indicates that the amino terminus is a site of significant structural diversity. To explore the role of the amino terminus of alpha 1C in expression and function of Ca2+ channels, we constructed a series of deletion mutants of the rabbit cardiac alpha 1C subunit and expressed them in Xenopus oocytes. Deletions of up to 120 amino acids from the amino terminus increased both ionic and gating currents by 5- to 8-fold. Ca2+ currents induced by these mutants had voltage-dependent activation, inactivation, modulation by beta subunits, and single channel conductance similar to the wild type cardiac alpha 1C (wt alpha 1C). Thus, deletion of a major portion of the amino terminus of alpha 1C did not alter the three dimensional conformation essential for channel function, but enhanced the expression of Ca2+ channels in Xenopus oocytes. A deletion mutant lacking the first 171 amino acids did not yield any measurable current.

Amino Acid Sequence↗
PubMed1995

Molecular determinants of cardiac Ca2+ channel pharmacology. Subunit requirement for the high affinity and allosteric regulation of dihydropyridine binding.

Cardiac L-type Ca2+ channels are multisubunit complexes composed of alpha 1C, alpha 2 delta, and beta 2 subunits. We tested the roles of these subunits in forming a functional complex by characterizing the effects of subunit composition on dihydropyridine binding, its allosteric regulation, and the ability of dihydropyridines to inhibit channel activity. Transfection of COS.M6 cells with cardiac alpha 1C-a (alpha 1) led to the appearance of dihydropyridine ([3H]PN200-110) binding which was increased by coexpression of cardiac beta 2a (beta), alpha 2 delta a (alpha 2), and the skeletal muscle gamma. Maximum binding was achieved when cells expressed alpha 1, beta, and alpha 2. Cells transfected with alpha 1 and beta had a binding affinity that was 5-10-fold lower than that observed in cardiac membranes. Coexpression of alpha 2 normalized this affinity. (-)-D600 and diltiazem both partially inhibited PN200-100 binding to cardiac microsomes, but stimulated binding in cells transfected with alpha 1 and beta. Again, coexpression of alpha 2 normalized this allosteric regulation. Therefore coexpression of alpha 1 beta and alpha 2 completely reconstituted high affinity dihydropyridine binding and its allosteric regulation as observed in cardiac membranes. Skeletal muscle gamma was not required for this reconstitution. Expression in Xenopus oocytes demonstrated that coexpression of alpha 2 with alpha 1 beta increased the potency and maximum extent of block of Ca2+ channel currents by nisoldipine, a dihydropyridine Ca2+ channel antagonist. Our results demonstrate that alpha 2 subunits are essential components of the cardiac L-type Ca2+ channel and predict a minimum subunit composition of alpha 1C beta 2 alpha 2 delta for this channel.

Allosteric Regulation↗
PubMed1995

Failure of high-dose oral acyclovir to suppress CMV viruria or induce ganciclovir-resistant CMV in HIV antibody positive patients.

Ninety-three symptomatic HIV antibody positive patients were randomized to receive zidovudine (ZDV) 600 mg/day and acyclovir (ACV) 4,800 mg orally per day versus ZDV 600 mg/day plus placebo. Urine was obtained at 3-month intervals and cultured for cytomegalovirus (CMV) in diploid fibroblast cells. The percent of urine specimens positive for CMV was 7.1% in the ZDV group and 5.8% in the ZDV plus ACV group (p = 0.55); 27% of patients had at least one urine culture positive for CMV while taking ZDV, versus 20% of patients taking the combination of ZDV plus ACV (p = 0.52). We conclude that ACV at a dosage of 4,800 mg/day does not suppress CMV excretion in urine of symptomatic HIV antibody positive patients taking concurrent ZDV. Use of ACV did not appear to induce resistance of CMV to ganciclovir since the ID50 of isolates from the two treatment groups did not differ.

Acyclovir↗
PubMed1995

Unimanual motor learning impaired by frontomedial and insular lesions in man.

We correlated impaired unimanual motor learning with the lesion site in 53 patients with chronic lesions predominantly of the frontal lobe. The lesions were assessed using computed tomography (CT), then transferred to standard templates of nine slices parallel to the canthomeatal plane and digitized with a raster matrix of 3 mm by 3 mm width. The learning task was to track a moving target on a computer screen with a dot guided by the preferred hand, while the horizontal coupling between hand movement and screen was inverted. The mean tracking error was recorded over eight successive trials of 80s duration. If the mean error of the last three trials was not lower than that of the first three trials, impaired motor learning was assumed. We correlated performance and lesion with a contingency table analysis for each raster element. Impaired motor learning was associated with a lesion within the supplementary motor area and adjacent anterior cingulate, and within the anterior insular region. Our results indicate that these regions are critical for motor learning and functional plasticity in man. Our data support activation patterns obtained with positron emission tomography.

Adolescent↗
PubMed1995

Mental representations of movements. Brain potentials associated with imagination of hand movements.

The present study was designed in order to contribute towards the understanding of the physiology of motor imagery. DC potentials were recorded when subjects either imagined or executed a sequence of unilateral or bilateral hand movements. The sequence consisted of hand movements in 4 directions, forwards, backwards, to the right and to the left, and varied from trial to trial. The sequence had been cued by visual targets on a computer screen and had to be memorized before the trial was initiated. Changes of DC potentials between task execution and imagination were localized in central recordings (C3, Cz, C4) with larger amplitudes when executing the task than when imagining to do so. Stimulation of peripheral receptors associated with task execution or a different level of activation of the cortico-motoneural system could account for this finding. The main result of the present study was that with unilateral performance, the side of the performing hand (right, left) had localized effects in recordings over the sensorimotor hand area (C3, C4) which were qualitatively the same with imagination and execution and quantitatively similar (i.e., without significant difference). Performance of the right hand augmented negative DC potentials in C3, performance of the left hand augmented amplitudes in C4. This result is consistent with the assumption that the primary motor cortex is active with motor imagery. Finally, the question has been addressed whether motor imagery may involve the left hemisphere to a larger extent than the execution of the movement. It is shown that a particular contribution of the left hemisphere associated with motor imagery may only show up under strictly controlled conditions.

Adult↗
PubMed1995

[Endoscopic dissection of perforating veins].

Endoscopic subfascial sectioning (ESDP) is an effective method for the interruption of incompetent perforating veins. From March 1993 to April 1994 27 patients underwent ESDP in 35 legs. ESDP was performed in combination with Babcock's operation in 31 cases. Most patients demonstrated chronic venous insufficiency stage II or III (n = 25). A venous ulcer was found in 9 patients. Intraoperative complications were not seen. Postoperative complications were delayed wound healing (n = 1) and subfascial hematoma (n = 1). At follow-up examination after a mean interval of 8 months persistent insufficient perforating veins were seen in 3 of 88 Cockett veins (4%). A local dysesthesia of the saphenous nerve was found in 6 legs. Prior active venous ulcers had healed in 8 of 9 cases.

Adult↗
PubMed1995

Further clinical studies of curdlan sulfate (CRDS)--an anti-HIV agent.

Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which inhibits the attachment of HIV to T-cells, and also has intracellular anti-HIV activity. In Phase I clinical trials, CRDS was found in 4 hr i.v. infusions, to be well tolerated up to 200 mg/70 kg and unexpectedly to produce marked, dose-related increases in CD4 lymphocytes in HIV-infected patients. Prolongation of bleeding time is expected to be the dose limiting toxicity, but no episodes of bleeding were seen. In one of the studies in this report, CRDS was administered i.v. daily for 7 days to HIV patients at doses of 40, 100, 140 and 180 mg/70 kg/day. At the higher doses, marked increases in CD4 and CD8 lymphocytes were observed. These increases mainly returned to baseline after 24 hr. To further delineate the pharmacokinetics of these changes in CD4 and CD8 lymphocytes, another Phase I study was done in which CRDS was infused i.v. over a 30 min period in HIV patients at single doses of 25, 50, 75, 100, 125, 150, 175 and 200 mg/70 kg/day. The drug was well tolerated in all cases and marked increases in CD4 lymphocytes were again seen at the higher doses, in some cases amounting to increases of 500 cells/mm3 after a single dose. The half-life of CRDS in man was found to be about two hours, as measured by activated partial thromboplastin time (APTT) and by plasma assays.

Antiviral Agents↗