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Biomedical subjects

C A Scott

Publications and source records attributed to C A Scott.

At least 19 recordsLinked to original sources

Is nocturnal paroxysmal dystonia a form of frontal lobe epilepsy?

The sex ratio, age at onset, and ictal features of nine patients with nocturnal paroxysmal dystonia were compared with those of eight patients with daytime frontal lobe seizures and eight patients with nocturnal motor attacks of known epileptic origin. All patients underwent video electroencephalography telemetry. There were no clinical features that would allow distinction between the groups and no single phenomenon was uniquely seen in nocturnal paroxysmal dystonia. This study provides no evidence that nocturnal paroxysmal dystonia is a separate diagnostic entity.

Adolescent

Measurement of interhemispheric time differences in generalised spike-and-wave.

We have compared interhemispheric time differences (ITD) calculated by coherence/phase and linear and non-linear correlation analyses of generalised spike-wave episodes in 30 patients (15 with primary generalised epilepsy (PGE), 5 with secondary generalised epilepsy (SGE) and 10 with a lateralised epileptogenic area). Most cases were recorded during routine departmental EEGs. No significant difference was found between measures of interhemispheric synchrony (IS) (proportion of ITDs that are synchronous) calculated using the linear and the non-linear correlation techniques, although the latter gave slightly more (average 7%) valid ITD estimates. This suggests that the non-linear correlation technique does not provide significantly more time difference information than its linear counterpart. Similarly, no significant differences in IS values were identified between the coherence/phase and the correlation techniques. For all 3 techniques, IS values greater than 50% were derived for most patients with PGE and SGE; the proportion of patients with a lateralised epileptogenic area showing this was smaller. However, broad overlap in the distribution of IS values between the 3 groups suggests that individual patients cannot reliably be distinguished using these methods.

Action Potentials

Beta-tubulin epitope expression in normal and malignant epithelial cells.

The expression of a unique beta-tubulin isoform (class III) was monitored in squamous cell carcinoma (SCC) and normal epithelial cells using a monoclonal tubulin antibody called TuJ1. Whole tissue homogenates of SCC, normal tissue, SCC grown in nude mice, and SCC cultured cells were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot. TuJ1 antibody localization was performed using peroxidase immunostaining on paraffin sections of SCC, normal tissue, nude mouse SCC, and immunofluorescent microscopy of SCC cultured cells. The malignant tissues examined stained positive with TuJ1 and a general beta-tubulin antibody, whereas the normal tissues stained positively only for the general beta-tubulin antibody. TuJ1 epitope expression may be a useful marker for SCCs and may assist in understanding differences between normal and malignant squamous cells.

Animals

Characterization of Leishmania major antigen-liposomes that protect BALB/c mice against cutaneous leishmaniasis.

Leishmania major antigen-liposomes prepared as dehydration-rehydration vesicles (DRV) and composed of equimolar amounts of L-alpha-distearoyl phosphatidylcholine and cholesterol confer high-level host-protective immunity against virulent homologous challenge to susceptible BALB/c mice. Physical and antigenic characterization of these protective liposomes is described. Both empty and L. major antigen-DRV were multilamellate and heterogeneous in size, ranging from 0.10 to 2.00 microns. Although the liposomes were made by using a crude mixture of promastigote antigens, lipophosphoglycan covered the liposome surface; this was demonstrated by immunogold electron microscopy. Application of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis revealed preferential entrapment of the 63-kilodalton promastigote protease (gp63) into the DRV. We suggest that our L. major antigen-DRV merit further study because of their preferential entrapment of these two host protective antigens together with their long in vivo half-life. In addition, this report illustrates that intravenous or subcutaneous immunization of BALB/c mice with the same limited subset of protective antigens, predominantly lipophosphoglycan and gp63, within DRV liposomes leads to either protection and low splenic interleukin-3 production or to nonprotection and high splenic interleukin-3 production, respectively. This was consistent with our hypothesis that differential antigen presentation after administration of the same immunogen by the intravenous or the subcutaneous route results in differential T-cell activation.

Animals

Vaccination against murine cutaneous leishmaniasis by using Leishmania major antigen/liposomes. Optimization and assessment of the requirement for intravenous immunization.

Efficacy of vaccination against cutaneous leishmaniasis in highly susceptible BALB/c mice was assessed comparatively by using radiation-attenuated promastigotes and colloidal Ag mixtures generated from a mixed Leishmania major (LV39) isolate (SLV39) and from a virulent cloned line (SVJ2) derived from the Jericho 2 L. major isolate. Dehydration-rehydration vesicle (DRV) liposomes were used as adjuvants. In optimization experiments phospholipid composition of DRV was varied, and the distearoyl derivative (DSPC) (liquid-crystalline phase transition temperature (Tc) 54 degrees C) of egg lecithin L-alpha-phosphatidylcholine was found to be superior to the dipalmitoyl derivative (DPPC, Tc 41.5 degrees C) and underivatized L-alpha-phosphatidylcholine (Tc -10 degrees C). The criteria studied were in vivo priming for a secondary in vitro proliferative response and the prepatency of lesion onset after L. major challenge of mice immunized once i.v. A single s.c. immunization with SLV39 either free or entrapped within DSPC liposomes primed spleen cells to produce significant levels of IL-3 when stimulated with SLV39 in vitro. In contrast, the i.v. route of immunization with the same Ag preparations led to little or no IL-3 production by the spleen cells. Despite development of significant T cell activation, both SLV39 and SVJ2 administered s.c., either free or entrapped within liposomes, were not protective. However, i.v. immunization four times with SVJ2 entrapped within DSPC liposomes induced a level of resistance comparable with that of 2 x 10(7) gamma-irradiated promastigotes in the stringent BALB/c L. major model. Although significant, protection conferred after i.v. immunization with SLV39/DSPC liposomes was less effective. These data therefore show that DSPC/DRV liposomes, although a good adjuvant for inducing protective immunity to cutaneous leishmaniasis, are not able to overcome the requirement for an i.v. route of immunization with the leishmanial Ag preparation. Additionally, they demonstrate a correlation between IL-3 secretion and non-protection. They also suggest that SVJ2 represents a better source of protective Ag than SLV39.

Adjuvants, Immunologic

The effects of theophylline on the physical performance and work capacity of well-trained athletes.

Theophylline, a pharmacologic agent presently permitted during international sporting competition, has come under scrutiny because of the suggestion that it may be ergogenic. This study examined the effects of serum theophylline levels of 10 to 20 mg/L and the administration of a placebo on selected measures of physical performance and work capacity to determine any ergogenic outcomes. Seven male and three female elite athletes from a variety of team sports and aged 18 to 30 years participated in the study. The variables measured were height, mass, maximal oxygen consumption, muscular endurance, muscular power, muscular strength, FVC, FEV1, and reaction time. When the scores obtained after ingestion of theophylline and a placebo with a double-blind, crossover technique were compared, no significant difference was found for any of these variables. A two-way analysis of variance of FEV1 scores obtained before and after maximal exercise revealed no significant "F" ratios. This indicated that none of these trained athletes demonstrated exercise-induced asthma and that there was no difference in airway resistance after maximal exercise while they were under the influence of theophylline or placebo. We conclude that no ergogenic effects were attributable to theophylline therapy which should therefore remain an acceptable means of management of athletes with asthma participating in international sporting events.

Adolescent

Rimiterol and the prevention of exercise-induced asthma.

The potential for rimiterol to protect athletes from exercise-induced asthma (EIA) has not been fully established. Ten athletes with asthma (15 to 30 years of age) undertook 8 minutes of submaximal exercise (80% of anaerobic threshold) on the treadmill ergometer, once after inhaling rimiterol and once after inhaling a placebo. Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test. Two puffs (400 micrograms) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test. Lung function measurements were made before exercise and immediately, 5, 10, 15, 20, 25, and 30 minutes after completion of exercise. The results of a two-way analysis of variance revealed significant (p less than 0.01) difference in the FEV1 scores obtained after rimiterol inhalation and placebo inhalation, 5, 10, 15, 20, 25, and 30 minutes after cessation of exercise. After inhalation of rimiterol, there were no significant changes in FEV1. After inhaling the placebo, significant reductions (p less than 0.01) in FEV1 occurred after cessation of exercise (5, 10, 15, and 20 minutes). All subjects exhibited EIA after placebo, and none after rimiterol. The mean maximum drop after exercise in FEV1 after inhalation of rimiterol (2.807 +/- 5.55) and placebo (24.54 +/- 8.4) was significantly different (t = 6.849). It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested.

Administration, Inhalation

Immunocytochemical profile of Kaposi's sarcoma cells: their reactivity to a panel of antibodies directed against different tissue cell markers.

Thirty-three cases of European Kaposi's sarcoma (KS) were investigated by immunohistochemical methods using a panel of antibodies specific for the markers of the cell types proposed for its histogenesis in the literature: S-100 protein for Schwann cells; lysozyme for histiocytes; alpha-actin, desmin and vimentin for pericytes and other mesenchyme-derived cells; factor VIIIR:Ag and Ulex europaeus agglutinin-I for endothelial cells. Antifibronectin antibodies were also used in order to investigate some functional activities of the proliferating cells. Immunohistochemical results showed that KS cells were diffusely positive for vimentin and alpha-actin and negative for all other cell markers. Furthermore, KS cells were constantly surrounded by fibronectin-positive material. Since the KS cells are diffusely positive for vimentin, they may be considered a monotypic proliferation of mesenchyme-derived cells which lack the markers of full endothelial cell differentiation; however, the occurrence of fibronectin-positive material around them suggests that these cells are actively proliferating endothelial cells and their diffuse positivity for alpha-actin suggests a possible differentiation to pericytic cells. In conclusion KS cells may be considered as mesenchymal cells which are at an intermediate stage of maturity or immaturity in vascular differentiation.

Actins

Hyaline bodies in Kaposi's sarcoma: an immunocytochemical and ultrastructural study.

The nature of hyaline bodies (HB) in Kaposi's sarcoma (KS) has been investigated by electron microscopy (EM) and immunohistochemical methods. Paraffin sections from 45 cases of KS selected on the basis of their high content of HB were challenged with antisera against factor VIIIR:Ag, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), alpha 1-antitrypsin (A1AT), fibrinogen, hemoglobin, alpha-actin and lysozyme. HB showed positivity for all the antibodies except for the last two. By EM, HB showed features consistent with red blood cell, fibrin and platelet phagocytosis. Therefore, HB in KS are considered to be the expression of an indiscriminate process of phagocytosis which involves not only erythrocytes and platelets, but also other substances such as fibrinogen, factor VIIIR:Ag, A1AT, CEA and AFP.

Antibody Specificity

Vimentin-typing in diagnostic surgical pathology: a comparative study using four antibodies after different fixations.

Vimentin-typing was carried out on various normal and neoplastic tissues using four anti-vimentin antibodies in order to evaluate the effect of different fixation treatments on tissue reactivity in comparison to the results obtained on frozen sections. All antisera were reactive on frozen material; on paraffin embedded material staining of tissues depended on the type of fixation method applied (formalin, methacarn or absolute alcohol) and each antibody behaved differently in relation to the fixative used. Only mesenchymal normal structures were revealed on frozen material whilst on paraffin embedded material three of the four antibodies reacted also with non-mesenchymal normal structures (epithelia, central and peripheral nervous system cells). All four antibodies decorated, regardless of treatment, neoplastic cells of mesenchymal and non-mesenchymal derivation, but not germ cells or germ cell tumors. The reactivity of vimentin to its specific antibodies depends on the fixative used: therefore, in routine pathology more than one antiserum should be available for testing. Furthermore, given the variety of non-mesenchymal structures stained by the anti-vimentin antibodies, the differential diagnosis of undifferentiated tumors must not be based on vimentin positivity alone. The expression of vimentin by non-mesenchymal neoplastic cells seems to parallel that of normal tissues during embryogenesis; therefore, this intermediate filament appears to be not only a marker of mesenchymal cells but also of many immature elements.

Antibodies, Monoclonal

9-alkyl anthracyclines. Absence of cross-resistance to adriamycin in human and murine cell cultures.

Four cell lines of human (CCRF CEM and U266BL) or murine (L1210 and P388D1) origin, resistant to the anthracycline antibiotic Adriamycin (doxorubicin) were selected in vitro from cultured cells by serial passage in the presence of Adriamycin. The resistant sublines were also cross-resistant to Mitoxantrone, 4'-epi Adriamycin and a number of novel anthracyclines including 4'-deoxy and 4'-methoxy analogues. However, a series of 9-alkyl substituted 4-demethoxyanthracyclines retained full activity against all the resistant sublines as did Aclacinomycin A. These results suggest that 9-alkyl substitution of 4-demethoxy-anthracyclines is an important determinant of activity against Adriamycin-resistant cell lines in vitro.

Animals

A method for localizing high-resolution NMR spectra from human subjects.

Several methods are available for the localization of high-resolution spectra. When the sample is a human subject, it may be difficult to realize a viable experimental protocol because the size and geometry of the subject often conflict with efficient probe design. In this paper a spectroscopic localization method is described which is based on the method of rotating frame imaging. A novel surface-coil probe has been developed so that this experiment can be performed on a large sample. 31P spectra from the thorax of a human subject are presented in which signals from liver and intercostal muscle are resolved. These data demonstrate that spatially resolved spectra of metabolites in vivo may be obtained in a time that is acceptable for patient examination.

Humans

A pseudolymphomatous reaction in soft tissue associated with phenytoin sodium.

A pseudolymphomatous reaction involving subcutaneous tissue and underlying skeletal muscle is described in a woman who was receiving phenytoin sodium and phenobarbitone. The histological appearance was of nodular, densely cellular tissue composed of histiocytes, plasma cells, lymphocytes, fibroblasts, and occasional polymorphonuclear cells. The significance of this finding is briefly considered in relation to the existing literature.

Adult