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Biomedical subjects

S E Smith

Publications and source records attributed to S E Smith.

At least 91 records · Page 5Linked to original sources
PubMed1994

Clonidine is not a useful adjunct to methadone gradual detoxification in opioid addiction.

BACKGROUND: The role of clonidine in the management of opioid-dependent individuals undergoing gradual detoxification. METHOD: A double-blind placebo-controlled trial was conducted on 86 voluntary in-patients (59 male, 27 female) aged 18-47 years, at a specialist drug-dependence treatment unit. Patients entered the trial when on 40 mg of methadone daily or less, and were randomised to receive incremental doses of clonidine (increasing from 0.2 mg daily to 1.2 mg daily) during a 14-day period of gradual methadone detoxification and for four weeks thereafter. Blood pressure was monitored and severity of opioid abstinence was assessed by questionnaire and by clinical examination. RESULT: Half the subjects were withdrawn or defaulted from the trial by the end of two weeks, those receiving clonidine earlier than those receiving dummy medication (9 of the former and only one of the latter because of systemic hypotension). Similar proportions of subjects completed detoxification in the two groups. In those who completed detoxification, clonidine did not significantly reduce either the symptoms or objective signs of opioid withdrawal. CONCLUSIONS: These findings suggest that clonidine has no place as an adjunct to a programme of gradual opioid detoxification.

Adolescent↗
PubMed1994

WISC-R subtest reliability over time: implications for practice and research.

This study investigated the test-retest reliabilities of the WISC-R IQs and scaled scores on subtests over 3- and 6-yr. intervals for a learning disabled sample. Statistical procedures and individual analyses were conducted on a sample of 107 students who had at least two evaluations. For the total sample, 3-yr. test-retest reliabilities of the Verbal IQ, Performance IQ, and Full Scale IQ were .69, .72, and .77, respectively. Subtest reliabilities ranged from .33 to .71, with a median of .49, but nine subtests had reliabilities of .62 or lower. Individual analyses indicated considerable variability, with some students decreasing as much as 33 IQ points on retest. Similar results were noted for a subsample of 41 students who had three evaluations over a 6-yr. period. Problems with subtest interpretation due to the inconsistency of the WISC-R scores and extensions of this research to the WISC-III are discussed.

Adolescent↗
PubMed1993

Nucleus of the solitary tract and dorsal motor nucleus of the vagus nerve of the pigeon: localization of peptide and 5-hydroxytryptamine immunoreactive fibers.

The distribution of peptide and serotonin fibers in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMNX) in the pigeon (Columba livia) was investigated immunocytochemically. This information was correlated with the viscerotopic organization of the nuclei and with central NTS circuitry to suggest the role of the neurochemical containing fibers in the regulation of organ function. The distribution of fibers containing cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), enkephalin (ENK), neuropeptide Y (NPY), neurotensin (NT), substance P (SP), somatostatin (SS), vasoactive intestinal peptide (VIP), and 5-hydroxytryptamine (5-HT) was determined. Each substance had a distinct distribution within the subnuclei of NTS-DMNX, but certain generalities can be deduced. In the DMNX, fibers immunoreactive for ENK, NT, and SP were found in greatest concentration, while CGRP and 5-HT immunoreactive fibers were the least dense. This suggests that ENK, NT, and SP may have a significant modulatory effect on gastrointestinal functions. In the NTS overall, ENK, NT, SP, and VIP fibers were found in high density, CCK, NPY, SS, and 5-HT fibers were found in moderate density, and CGRP fibers were found in low density. However, some individual NTS subnuclei were found to contain moderate to high concentrations of each of the substances, including CGRP. Fibers containing CCK, ENK, NT, SP, SS, and VIP in the medial dorsal NTS subnuclei may regulate gastroesophageal functions. The caudal part of subnucleus lateralis parasolitarius did not contain most of the substances, which suggests that pulmonary function is not modulated by these neurochemicals. The boundaries of a subnucleus could sometimes be demarcated by a change in density of immunoreactive fibers between adjacent subnuclei. This was particularly evident in NTS subnuclei medialis dorsalis anterior centralis and lateralis parasolitarius, and in DMNX subnucleus posterior dorsalis magnocellularis. The selective distribution of peptide and serotonin immunoreactive fibers in various subnuclei of NTS-DMNX suggests that these substances may be differentially involved in neural circuits that mediate cardiovascular and gastrointestinal functions.

Animals↗
PubMed1993

Structure and regulation of the growth arrest-specific (gas-1) promoter.

We have isolated recombinant genomic clones encompassing several kilobase pairs of the 5'-flanking regions of both the human and murine gas-1 gene (growth arrest-specific gene 1). Both species share a highly conserved region of approximately 550 base pairs upstream of the gas-1 transcription start site. Deletion analysis of the murine gas-1 promoter demonstrated that a fragment containing the first 665 base pairs is sufficient to drive the serum-regulated expression of a luciferase reporter gene in NIH3T3 cells, in a manner qualitatively reflecting the activity of the endogenous gene. Gel retardation assays indicated the presence of a number of DNA-binding proteins specific for sequences contained within the gas-1 transcription regulatory region. Comparative studies with extracts prepared from growing and resting cells revealed several growth state-specific binding activities. One promoter fragment that bound prominent growth- and arrest-specific complexes was further analyzed by copper-phenanthroline footprinting. It was found that the same DNA element is a target both for growth- and for arrest-specific activities. The factors characterized in this study are the first candidates for transcriptional regulators mediating cell growth-specific repression and/or growth arrest-specific activation of gene expression.

3T3 Cells↗
PubMed1993

Cerebroprotective effect of BW619C89 after focal or global cerebral ischaemia in the rat.

BW619C89 (4-amino-2-(4-methylpiperazin-l-yl)-5-(2,3,5-trichlorophenyl) pyrimidine) was evaluated for cerebroprotection after focal or global ischaemia. BW619C89, as the mesylate dihydrate salt, 20 mg kg-1, i.v. for 10 min immediately, or with a 1 h delay after permanent middle cerebral artery occlusion in Fischer rats reduces cortical infarct volume (visualized with (2,3,5-triphenyltetrazolium) by 49% (p < 0.05) or by 61% (p < 0.001) and improves neurological deficit. Administration of BW619C89 with a 2 h delay is ineffective. BW619C89, given i.p. 0 and 4 h after 20 min of transient bilateral common carotid artery occlusion in vertebral artery-occluded Wistar rats reduces glutamate release and neuronal cell loss in the hippocampal CA1 sector (p < 0.01) and striatum (p < 0.05). BW619C89 resembles BW1003C87 (5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine) in inhibiting veratrine-induced glutamate release and protecting against ischaemic brain damage.

Animals↗
PubMed1993

Different TRE-related elements are distinguished by sets of DNA-binding proteins with overlapping sequence specificity.

Several promoter elements with sequence similarity to the prototype TPA-responsive element (TRE) were compared by mobility-shift analyses. Activities within whole cell extracts were identified that bind to the TRE-like elements in the collagenase, the somatostatin, and the c-jun promoters. The corresponding factors appeared to differ in their degree of selectivity for these TRE-like sequences. One protein species bound equally well to all TREs. In addition, a subset of specific activities recognised only the somatostatin and the c-jun-derived element and one DNA-protein complex had exclusive specificity for the TRE present in the c-jun promoter. By antibody 'supershift' assays some of the protein components of the specific complexes were identified as CREB- and ATF-related products. Based on these data we postulate that bZip protein dimers differ in their ability to tolerate variations from the canonical TRE sequence. We propose that TRE-like promoter elements are distinguished by this ability to bind to different subsets of a family of related transcription factors.

Animals↗
PubMed1993

Distribution, parabrachial region projection, and coexistence of neuropeptide and catecholamine cells of the nucleus of the solitary tract in the pigeon.

The chemical nature of the cells of the nucleus of the solitary tract (NTS) that project to the parabrachial nucleus (PB) was investigated in the pigeon by the use of fluorescent bead retrograde tracer and immunofluorescence for the detection of substance P (SP), leucine-enkephalin (LENK), cholecystokinin (CCK), neurotensin (NT), somatostatin (SS), and tyrosine hydroxylase (TH). Cells immunoreactive for CCK were located in subnuclei lateralis dorsalis pars anterior (LDa) and medialis superficialis pars posterior, and caudal NTS (cNTS); 22-26.5% of these cells were double-labeled bilaterally. Immunoreactive SP cells were found in ventral NTS subnuclei; 24-25% of these cells were double-labeled bilaterally. Cells immunoreactive for LENK and NT were concentrated in the anterior NTS; 5.5-7.5% of the LENK cells were double-labeled bilaterally, while 11% (ipsilateral) and 21% (contralateral) of the NT immunoreactive cells were double-labeled. Many SS immunoreactive cells were found in peripherally located subnuclei; 5.5-6.5% of these cells were double-labeled bilaterally. Catecholamine cells were distributed in LDa, peripheral subnuclei, and cNTS; 23% of these cells were double-labeled ipsilaterally and 8.5% contralaterally. A two-color double-labeling immunofluorescence technique revealed many cells immunoreactive for both NT and LENK, only a rare cell immunoreactive for both SS and SP, and no cells immunoreactive for both TH and SP. Cells immunoreactive for SP, CCK, NT, and TH are major contributors to NTS projections to PB. The confinement of these substances to specific NTS subnuclei, which receive visceral sensory information from specific organs, may contribute to the chemical encoding of ascending visceral information.

Animals↗
PubMed1993

Cloning and characterization of the human t(3;6)(p14;p11) translocation breakpoint associated with hematologic malignancies.

The t(3;6)(p14;p11) chromosome translocation was identified in a family in which three members developed hematologic malignancies. To help characterize the region on chromosome 3 surrounding this translocation breakpoint, two flanking lambda clones, MS156 and MJ1525, were linked by pulsed-field gel electrophoresis to the same 510-kb NotI fragment on chromosome 3. MS156 was localized to a region proximal to the breakpoint of a der(3) chromosome somatic cell hybrid (derived from the t(3;6) cell line), and MJ1525 localized distal to the breakpoint. MJ1525 was used to screen the CEPH yeast artificial chromosome (YAC) library, which revealed a YAC, 195F3, that spanned the breakpoint. Subcloning into Lambda DASH II and production of a contiguous array of overlapping lambda clones revealed a clone, L17, that spanned the breakpoint. A rare restriction endonuclease map for the YAC 195F3 was constructed, and multiple clusters of rare restriction sites within the YAC were identified, possibly indicating the disruption of a gene by the t(3;6) translocation breakpoint.

Animals↗
PubMed1993

Acute and chronic anticonvulsant effects of D(-)CPPene in genetically epilepsy-prone rats.

Acute administration (0.4-12 mumol/kg, i.p.) of the NMDA antagonist D(-)CPPene (3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid; molecular weight = 250.2) dose-dependently reduced the incidence of sound-induced clonic seizures in genetically epilepsy-prone (GEP) rats. The ED50 value against clonic seizure at +1 h was 2.6 (2.2-3.2) and at +4 h was 1.7 (1.3-2.3) mumol/kg (i.p.). Twelve hours after chronic administration of an anticonvulsant dose of D(-)CPPene (4 mumol/kg, i.p., twice daily at 09.00 and 21.00 h, for 14 days), repeat administration of D(-)CPPene (1.2-12 mumol/kg, i.p.) gave ED50 values against clonic seizure at +1 h of 3.4 (2.5-4.8) mumol/kg and at +4 h of 2.8 (2.0-3.9) mumol/kg (i.p.). There was no significant difference observed between ED50 values for these acute and chronic groups. The duration of the anticonvulsant effect observed between +1 h and +8 h after D(-)CPPene (0.4-12 mumol/kg, i.p.) was similar in the acute and chronic groups. The ED50 values for D(-)CPPene-induced impairment of locomotor performance (using a rotarod) at +3 h were 6.8 (4.4-10.4) and 6.4 (4.1-10.1) mumol/kg (i.p.) for the acute and chronic groups respectively. At +7 h after D(-)CPPene administration the ED50 value for locomotor impairment was 19.5 (10.6-36.0) mumol/kg (i.p.) in the acute group. In this study there is no evidence of tolerance to the anticonvulsant effects and little evidence of tolerance to the adverse effects (ataxia) of D(-)CPPene in GEPRs.

Animals↗
PubMed1993

Excitatory amino acid antagonists, lamotrigine and BW 1003C87 as anticonvulsants in the genetically epilepsy-prone rat.

Sound-induced seizures in genetically epilepsy-prone rats were used to compare the anticonvulsant effect of phenytoin and diazepam with compounds which decrease glutamatergic neurotransmission including excitatory amino acid antagonists acting at N-methyl-D-aspartate (NMDA) receptors: D(-)CPPene, CGP 37849 and MK 801 or at the glycine/NMDA site: ACPC (1-aminocyclopropane-dicarboxylic acid) (partial agonist) or non-NMDA receptors: NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]-quinoxaline.Li) and GYKI 52466 (1-(aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazepin e.HCl) or acting at sodium channels to decrease glutamate release: lamotrigine and BW 1003C87 (5(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine ethane sulphonate). ED50 values against clonic seizures (in mumol/kg at the time of peak anticonvulsant effect) were: phenytoin 30.5 (2 h), diazepam 0.5 (0.5 h), MK 801 0.01 (4 h), D(-)CPPene 1.9 (4 h), CGP 37849 2 (1 h), GYKI 52466 24 (0.25 h), NBQX 40 (0.5 h), ACPC 1053 (0.5 h), BW 1003C87 2.2 (1 h), lamotrigine 4.8 (4 h). BW 1003C87, lamotrigine, MK 801, phenytoin, diazepam and CGP 37849 had the most favourable therapeutic indices (rotarod locomotor deficit ED50/anticonvulsant ED50).

2-Amino-5-phosphonovalerate↗
PubMed1993

Proconvulsant and anticonvulsant effects of Evans blue dye in rodents.

The effect of i.c.v. administration of Evans blue to sound sensitive DBA/2 mice and to genetically epilepsy-prone rats was studied. In mice, Evans blue (3.3-52 nmol) induced: hyperlocomotion, wild running, scratching, clonic muscle spasms, tonic seizure (latency 10-45 min), followed by death or recovery. The CD50 value for clonic seizures for Evans blue was 35(23-53) nmol. Pretreatment (45 min) with Evans blue (13-52 nmol, i.c.v.) dose-dependently reduced the incidence of sound-induced seizures in DBA/2 mice (ED50 value against clonic seizures = 30 [15-58] nmol, i.c.v). In rats, Evans blue (104 nmol, i.c.v.) induced electroencephalographic seizures in the hippocampus and cortex and behavioural limbic seizures with a latency of 15-20 min. A reduction in the mean score (from 5 to 2-3) for behavioural seizures was observed which lasted for 4-5 days in rats electrically-kindled daily in the hippocampal CA3 subsector. Sound-induced clonic seizures in kindled and non-kindled rats were reduced for 3-4 days after administration of Evans blue (104 nmol, i.c.v.).

Acoustic Stimulation↗
PubMed1993

Cardiovascular and sweating dysfunction in patients with Holmes-Adie syndrome.

A cross-sectional study is reported in which 53 patients with Holmes-Adie syndrome have been subjected to a battery of tests of autonomic nervous function referable to the cardiovascular system, to two objective tests of sweating function, and to subjective assessment of sweating by application of quinizarin powder followed by body heating. The majority of patients were consecutive referrals; none was selected because of clinical indications of autonomic dysfunction. Eighty three per cent of these patients had at least one, 57% at least two, and 40% at least three objective test abnormalities, as defined by values lying outside 95 percentiles of healthy subjects who were matched for age and subjected to the same tests. In the context of multiple testing, the probability of finding outside values was such that a minimum of 3 was required to define abnormality. On this basis 40% of patients were found to have significant evidence of autonomic dysfunction. The most frequent abnormalities were impaired digital vasoconstriction to cold (23%), a reduced heart rate response to the Valsalva manoeuvre (17%), and excessive variability in sweating between test sites (in one of the tests, 43%) which is consistent with patchy loss. Abnormal quinizarin test appearances were seen in 10 patients and in a further five patients the appearances were thought to be suggestive of abnormality. Though assessment of the results of this test are subjective, the observations are consistent with the findings obtained from the objective tests which were applied. Cardiovascular and sweating abnormality did not concur significantly and only the former was found to increase progressively with known duration of the pupillotonia. It is concluded that Holmes-Adie syndrome is commonly accompanied by progressive mild but widespread autonomic involvement but rarely is this symptomatic. If symptoms suggestive of autonomic neuropathy are found in a patient with tonic pupils, a careful search for some other generalised disorder is recommended.

Adie Syndrome↗
PubMed1993

Alginate may accumulate in cystic fibrosis lung because the enzymatic and free radical capacities of phagocytic cells are inadequate for its degradation.

We sought an explanation for the accumulation, and apparent poor degradation by alveolar phagocytes, of alginate in cystic fibrosis lung. A crude intracellular lyase preparation extracted from Klebsiella pneumoniae was able to degrade seaweed alginic acid as well as forms purified from Pseudomonas aeruginosa bacteria from Cystic Fibrosis (CF) patient lungs. This was by a beta-eliminative mechanism, as detected by an increase in the 232nm absorbance and activity was enhanced by deacetylation of the Pseudomonas aeruginosa alginates. Conditioned media or cell lysates from unstimulated or triggered phagocytic cells (including resident mouse peritoneal macrophages and the human macrophage cell line U937) had no effect in the same system. Free radicals generated by chemical systems or by gamma irradiation of water degraded alginate. Depolymerisation by free radicals, as detected by viscosity determinations and polyacrylamide gel electrophoresis, generated a wide range of fragment sizes. In contrast, mouse peritoneal macrophages or human polymorphonuclear neutrophils stimulated to generate free radicals had no significant effect on alginate. Under the conditions of our experiments, phagocytic cells representative of the CF lung are not able to degrade Pseudomonas aeruginosa alginate. This may explain the gross accumulation of alginate in CF lung.

Alginates↗
PubMed1993

Absence of human papillomavirus in squamous cell carcinomas of nongenital skin from immunocompromised renal transplant patients.

BACKGROUND AND DESIGN: Human papillomavirus (HPV) is accepted as a factor in the pathogenesis of genital squamous cell carcinomas. The incidences of both HPV infection and squamous cell carcinoma are increased in immunocompromised renal transplantation patients. The purpose of this study was to determine if HPV DNA is present in squamous cell carcinomas of nongenital skin in immunosuppressed patients. Amplification of HPV DNA was performed using the polymerase chain reaction. The sensitivity and specificity of the polymerase chain reaction was assessed on 19 positive and six negative control specimens. Twenty genital squamous cell carcinomas from nonimmunocompromised patients and 28 nongenital squamous cell carcinomas from renal transplantation patients were then analyzed. RESULTS: Human papillomavirus DNA was identified in 18 of 19 positive control specimens and zero of six negative control specimens. Human papillomavirus DNA was identified in four of 20 genital squamous cell carcinoma specimens. In comparison, no HPV DNA was identified in 28 nongenital squamous cell carcinomas from immunosuppressed hosts (Fisher's Exact Test, P < .025). CONCLUSIONS: These findings support a role for HPV in genital skin cancers and suggest that HPV does not play a role in the increased incidence of squamous cell carcinoma in renal transplantation patients.

Carcinoma, Squamous Cell↗
PubMed1993

Cognitive deficits associated with fragile X syndrome.

Recent research has identified fragile X syndrome as the second leading cause of mental retardation. A unique profile of behavioral patterns and cognitive deficits associated with this disorder has gradually emerged. Current published literature has become repetitive with physical and clinical characteristics of this syndrome. Educators, however, have failed to adequately address or clarify learning approaches and remediation strategies that are necessary to develop appropriate training and educational programs. Current research on cognition among individuals with fragile X syndrome was reviewed and intervention strategies discussed that should be considered in the development of programs for these individuals.

Cognition Disorders↗
PubMed1993

Participatory action-research for health.

Participatory action-research, developed primarily by peoples of the Third World, combines adult education with investigation and sociopolitical action. With the goal of personal and social transformation it builds on the capacity of people to think and work together for a better life and the equitable sharing of knowledge, skills and resources so as to support fair social structures, which, ultimately, are health determinants.

Community Participation↗
PubMed1993

A comparison of the laser flare cell meter and fluorophotometry in assessment of the blood-aqueous barrier.

PURPOSE: To evaluate and compare the use of the Kowa laser flare cell meter and intravenous anterior chamber fluorophotometry in assessment of the blood-aqueous barrier after cataract surgery. METHOD: Laser flare and cell measurements and fluorophotometry were performed at 1 and 3 months after surgery in 48 eyes of 44 patients admitted for routine cataract surgery. The fellow pseudophakic eyes of these patients were used as controls. RESULTS: The two techniques measure different parameters, but both methods are able to document the integrity or breakdown of the blood-aqueous barrier. However, the laser flare cell meter is more sensitive in quantifying subtle changes in barrier function to large molecules (proteins). Various methods of assessing anterior chamber fluorophotometry data were also compared. Measurement of a diffusion coefficient (requiring the measurement of plasma fluorescence) was not found to be more sensitive than other methods and did not alter the clinical significance of data obtained from the measurement of anterior chamber fluorescence alone. CONCLUSIONS: Both the laser flare cell meter and fluorophotometry provide a method for the assessment of the postoperative blood-aqueous barrier. However, the laser flare cell meter is rapid, noninvasive, and relatively easier to use. Therefore, for clinical use, it has great practical advantages over fluorophotometry.

Adult↗