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Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 163 records · Page 9Linked to original sources

Separation of parasite antigens by molecular exclusion, anion exchange, and chromatofocusing utilizing FPLC protein fractionation systems.

Excretory-secretory products (ESP) were harvested from balanced salt solutions in which adult Fasciola hepatica had been incubated for 4-6 h at 37 degrees C. The ESP was fractionated by standard low pressure molecular exclusion chromatography and FPLC (fast protein liquid chromatography) using the principles of molecular exclusion, anion exchange, and chromatofocusing. The dot-enzyme-linked immunosorbent assay (Dot-ELISA) was used to demonstrate the immunoreactivity of eluted fractions. Compared to Sephacryl S-200, separation by Superose-6 (FPLC) was faster and resolved more peaks (four with Sephacryl S-200 and nine with Superose-6). Peaks from Sephacryl S-200 were resolved by the first anion exchange (Mono Q) separation into seven peaks; when these peaks were subjected to a second anion exchange, 15 peaks were resolved. Thirty-eight peaks were resolved by chromatofocusing (Mono P) in the pH range 7-4. Immunoreactive fractions from narrow-range (single pH unit) chromatofocusing were identified by the Dot-ELISA. The FPLC system proved to be a means of rapid and high resolution separation of F. hepatica antigens.

Animals↗

Anticonvulsant activity of 2- and 3-aminobenzanilides.

A series of 2- and 3-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazole and in the rotorod assay for neurologic deficit. The 3-aminobenzanilide derived from 2,6-dimethylaniline, 21, was the most potent anti-MES compound, with an ED50 of 13.48 mg/kg and a protective index of 21.11 (PI = TD50/ED50). The activity profile for 21 compares favorably with that for phenobarbital and phenytoin.

Anilides↗

A study of the cerebral cortex cholecystokinin receptor using two radiolabelled probes: evidence for a common CCK 8 and CCK 4 cholecystokinin receptor binding site.

This study was directed at the issue of whether or not subpopulations of cholecystokinin (CCK) receptors exist within the CNS. This was achieved through the use of two radiolabelled probes, namely [125I] Bolton-Hunter (BH) CCK 8 and [3H]pentagastrin (Boc-beta-Ala CCK 4), in comparative studies under identical conditions. Both probes bound with high affinity to the mouse cerebral cortical CCK receptor binding site with apparent equilibrium dissociation constants (KD) of 1.9 nM and 1.4 nM for [3H]pentagastrin and [125I]BH CCK 8, respectively. The maximal binding capacity was 1.05 and 1.15 pmol/g weight for the tritium and iodinated probes, respectively. Hill analysis yielded Hill numbers close to unity, suggesting the absence of more than one binding site and the lack of cooperativity of CCK receptor binding. Kinetic studies revealed binding site homogeneity in that no evidence of multiphasic dissociation curves was seen. Computerised analysis of displacement binding data using LIGAND established that both radiolabelled probes bound to a single site, with the one-site model providing the best fit of the data. Similar rank orders of potency were obtained for various fragments of CCK 8 in competing for the CCK receptor, labelled with either probe. Both CCK 8 and CCK 4 bound with roughly equinanomolar affinity. These studies demonstrate that both CCK 8 and its shorter C-terminal fragment CCK 4 bind to a single class of high-affinity binding site, with as yet no evidence of CNS CCK receptor multiplicity.

Animals↗

Posterior atlantooccipital subluxation in Down syndrome.

Three Down syndrome patients with posterior atlantooccipital (AO) subluxation are described. All are asymptomatic. The subluxation becomes manifest during active extension of the neck and reduces in flexion. Methods of assessing posterior AO subluxation are discussed. The abnormality is attributed to ligamentous laxity in patients with Down syndrome.

Adolescent↗

Resolution of some enantiomeric amines of forensic interest by high-performance liquid chromatography.

The high-performance liquid chromatographic resolution of the enantiomers of amphetamine, methamphetamine, ephedrine, and pseudoephedrine is described. The sugar isothiocyanate, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC), is used as a chiral derivatizing agent, with chromatographic separations of the diastereomers formed with each amine made using a standard achiral C18 stationary phase.

Amines↗

Unusual responses of cultured Fundulus heteroclitus melanophores to epinephrine and ions, paradox of K+ versus Na+.

Fundulus heteroclitus melanophores were successfully cultured and maintained in culture for up to 2 months. Compared to other teleost melanophores in the fin, scale, or split fin preparation, the cultured melanophores show unusual responses to both epinephrine and ion solutions. First, they aggregated their melanosomes in response to concentrations of epinephrine as low as 10(-12) M. Second, the melanophores in a 6-day, or older, culture aggregated their melanosomes in response to both sodium and potassium ion solutions. This is in contrast to 4-day-old cultures (and reports of noncultured melanophores) where melanosomes are aggregated in response to potassium but dispersed in sodium ion solutions.

Adrenocorticotropic Hormone↗

Fixed atlantoaxial rotary deformity with bilateral facet dislocation.

A 21-year-old patient with Down syndrome who developed rotary atlantoaxial dislocation of C1 and C2 following an upper respiratory infection is presented. Techniques for detection and quantification of this potentially serious dislocation using multidirectional tomography and computerized tomography are described.

Adult↗

Sensitivity to noise in a community sample: I. Measurement of psychiatric disorder and personality.

A sample of 77 women of high and low noise sensitivity, living in areas of high and low exposure to aircraft noise drawn from the 1977 West London Survey, were interviewed in the community in 1980. Women of high, intermediate and low noise sensitivity in 1980 were compared for measures of psychiatric disorder, personality and reactivity to the other sensory stimuli. In addition, the noise sensitivity measures defining the three groups in 1980 were compared with further measures of noise sensitivity. High noise sensitive women exhibited significantly more psychiatric symptoms, higher neuroticism scores, and greater reactivity to other sensory stimuli than intermediate and low noise sensitive women.

Adolescent↗

Sensitivity to noise in a community sample: II. Measurement of psychophysiological indices.

A sample of 77 women of high and low noise sensitivity in 1977, living in areas of high and low exposure to aircraft noise, were interviewed in the community in 1980. High, intermediate and low noise sensitive women were compared, using measures of blood pressure, heart rate, skin conductance, hearing threshold, uncomfortable loudness level and magnitude estimation of six tones. These physiological measures did not clearly distinguish different noise sensitivity groups, except that highly noise sensitive women had a consistently slower heart rate. Noise sensitivity was not related to auditory threshold. In the high aircraft noise area there were significantly more skin conductance responses than in the low aircraft noise area irrespective of noise sensitivity. This may be the result of chronic exposure to high aircraft noise.

Adolescent↗

Anticonvulsant activity of some 4-aminobenzanilides.

A series of 4-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and metrazole (pentylenetetrazole) and in the rotorod assay for neurologic deficit. All of the 4-aminobenzanilides showed activity at doses of 300 mg/kg against maximal electroshock seizures (MES). The 4-aminobenzanilide derived from 2,6-dimethylaniline (8) was the most potent anti-MES compound with an ED50 of 2.60 mg/kg and a protective index of 5.77 (PI = TD50/ED50). The activity profile for 8 compares quite favorably with that for phenobarbital and phenytoin in the same assays.

Anilides↗

Liquid chromatographic determination of the enantiomeric composition of amphetamine and related drugs by diastereomeric derivatization.

A procedure is described for the derivatization of amphetamine and methamphetamine enantiomers with 4-nitrophenylsulfonyl-(S)-prolyl chloride. The resulting diastereomeric amphetamine derivatives were resolved by a reversed-phase procedure. The derivatization yield was maximized in the 95% range using a five-fold molar excess of the chiral derivatizing agent and an approximate 18 to 1 ratio of base (NaHCO3) to total acid generated in the reaction.

Amphetamine↗

Biomechanical study of cervical spine stabilization with methylmethacrylate.

Polymethylmethacrylate (PMMA) has been used to provide immediate fixation in the spine, especially in the cervical region. With its use spreading to nontumor cases and a younger patient population, its biomechanical contribution to the stability and strength of the injured spine becomes increasingly important. The present study is unique, as it provides, for the first time, results of a three-dimensional stability and flexion strength testing of a surgical specimen removed at autopsy after 7 years. Also tested, in the identical manner, is a normal specimen to provide control data. The PMMA specimen, as compared with the control, was generally found to have less motion. Its flexion strength was at par with that of the control, although it did not exhibit the initial low-stiffness region of the normal spine specimen.

Biomechanical Phenomena↗

Odontoid upward migration in rheumatoid arthritis. An analysis of 45 patients with "cranial settling".

Lack of correlation between the severity of rheumatoid subluxation of the upper cervical vertebrae and supposed absence of neurological damage has led to the erroneous supposition that this finding is innocuous. Incomplete autopsy studies in rheumatoid arthritis have failed to recognize the cause of death, despite previously proven dramatic occipito-atlanto-axial dislocations. The most feared entity of rheumatoid basilar invagination, namely "cranial settling," is poorly understood. Between 1978 and 1984, the authors treated 45 rheumatoid arthritis patients who were symptomatic with "cranial settling." This consisted of vertical odontoid penetration through the foramen magnum (9 to 33 mm), occipito-atlanto-axial dislocation, lateral atlantal mass erosion, downward telescoping of the anterior arch of C-1 on the axis, and rostral rotation of the posterior arch of C-1 producing ventral and dorsal cervicomedullary junction compromise. Cervicomedullary junction dysfunction has mistakenly been called "entrapment neuropathy," "progression of disease," or "vasculitis." Occipital pain occurred in all 45 patients, myelopathy in 36, blackout spells in 24, brain-stem signs in 17, and lower cranial nerve palsies in 10. Four patients had prior tracheostomies. Four previously asymptomatic patients with "cranial settling" presented acutely quadriplegic. The factors governing treatment were reducibility and direction of encroachment determined by skeletal traction and myelotomography. Transoral odontoidectomy was performed in seven patients with irreducible pathology. All patients underwent occipitocervical bone fusion (with C-1 decompression if needed) and acrylic fixation. Improvement occurred during traction, implying that compression might be the etiology for the neurological signs. There were no complications. Thus, "cranial settling" is a frequent complication of rheumatoid arthritis; although it is poorly recognized, it has serious implications and is treatable.

Aged↗

The induction of tolerance to thyroglobulin significantly reduces the severity of thyroiditis in obese strain chickens.

Obese strain chickens develop severe spontaneous autoimmune thyroiditis several weeks after hatching, characterized by mononuclear cell infiltration and antibodies to thyroglobulin (Tg). The presence of antibodies to Tg suggests that Tg is an important antigen in this disease, but it does not provide definitive evidence. To clarify this point, Obese strain chicks were tolerized at hatching with Tg and then examined up to 6 wk later for antibodies to Tg, thyroid pathology, and function. Various tolerance regimens were tested. The optimal conditions were i.v. injection of Tg within 24 hr of hatching, and injection of at least 1 mg. Tg isolated from normal thyroid glands was satisfactory, and it did not have to be deaggregated. Tolerance induced by the above procedure significantly retarded all parameters of autoimmunity, although by 6 wk of age some of the tolerized chicks had severe thyroiditis. Multiple weekly injections of Tg were no more effective than a single injection at hatching. Interestingly, a single injection at hatching was very effective, yet it was cleared from the circulation within 24 hr. In summary, tolerance induced with Tg had a profound effect on the disease and thus provides good evidence for the role of Tg in this disease.

Animals↗

Diagnosis of ovine fascioliasis by a dot enzyme-linked immunosorbent assay: a rapid microdiagnostic technique.

A microenzyme-linked immunosorbent assay (dot-ELISA) was modified for making an immunodiagnosis of Fasciola hepatica infections in sheep. Sheep were alloted as follows: group I-3 controls and 4 principals, each inoculated with 500 metacercariae; group II-3 controls and 7 principals, each inoculated with 250 metacercariae; and group III-3 controls and 7 principals, each inoculated with 500 metacercariae. Blood and fecal samples were collected from each animal every 2 weeks for 16 weeks. Presence (or absence) of flukes was confirmed by fecal examinations and examination of dissected livers at necropsy of the sheep. The dot-ELISA incubations were done at ambient room temperature. Nitrocellulose disks dotted with 1 microliter (50 ng of protein) of F hepatica excretory/secretory products were placed in 96-well tissue culture plates. After nonspecific binding sites on the disks were bound with bovine serum albumin-triethanolamine-buffered saline solution, dilutions (1:2) of positive- and negative-control serum samples or experimental serum samples were placed in appropriate wells for a 30-minute incubation. Wells were washed (3 times), and 50 microliters of horseradish peroxidase conjugated rabbit anti-sheep immunoglobulin G was added to each well for a 30-minute incubation and then aspirated. Substrate solution (4-chloro-1-naphthol, methanol, triethanolamine-buffered saline solution, and H2O2; 50 microliters) was added for a 30-minute incubation and then aspirated. Disks were air dried for visualization: solid purple dot = positive sample, or no dot = negative sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗