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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 109 records · Page 6Linked to original sources
PubMed1999

Physiology of perception: cortical stimulation and recording in humans.

OBJECTIVES: 1) To determine the effect of stimulus train duration (TD) on sensory perception using direct stimulation of somatosensory and visual cortices. 2) To investigate the occurrence of evoked potentials in response to stimulation that is subthreshold for perception. BACKGROUND: Studies of the mechanisms of conscious perception using direct cortical stimulation and recording techniques are rare. The clinical necessity to implant subdural electrode grids in epilepsy patients undergoing evaluation for surgery offers an opportunity to examine the role of stimulus parameters and evoked potentials in conscious perception. METHODS: Subjects included epilepsy patients with grids over somatosensory or occipital cortex. Single pulses (100 microseconds) and stimulus trains were applied to electrodes, and thresholds for perception were found. Evoked potentials were recorded in response to peripheral stimulation at intensities at, above, and below sensory threshold. RESULTS: During cortical stimulation, sensory threshold changed little for stimulus trains of 250 milliseconds and longer, but increased sharply as TD decreased below this level. Primary evoked activity was recorded in response to peripheral stimulations that were subthreshold for conscious perception. CONCLUSIONS: The results confirm a previous report of the effects of stimulus TD on sensory threshold. However, no motor responses occurred following somatosensory stimulation with short trains, as previously reported. The TD threshold pattern was similar in visual cortex. In agreement with the previous report, early components of the primary evoked response were not correlated with conscious sensory awareness.

Adolescent↗
PubMed1999

Cloning and characterization of CRF, a novel C1q-related factor, expressed in areas of the brain involved in motor function.

We have isolated and characterized a novel cDNA, C1q-Related Factor (CRF), that is predicted to encode a 258 amino acid polypeptide with a hydrophobic signal sequence, a collagenous region, and a globular domain at the carboxy terminus that shares homology to the C1q signature domain. Human CRF transcript is expressed at highest levels in the brain, particularly in the brainstem. In situ hybridization to mouse brain sections demonstrated that CRF transcripts are most abundant in areas of the nervous system involved in motor function, such as the Purkinje cells of the cerebellum, the accessory olivary nucleus, the pons and the red nucleus. The mouse CRF homolog is highly similar to the human gene at both the nucleotide and protein level, suggesting an important conserved role for this protein.

Amino Acid Sequence↗
PubMed1999

Development of an in vitro screening method for evaluating decontamination of sulfur mustard by reactive dermal formulations.

New barrier creams known as topical skin protectants (TSPs) recently have been formulated and demonstrated to be effective in delaying skin penetration of the blistering warfare agent sulfur mustard (HD). To further inactivate or neutralize HD, compounds that react with the toxic agent must be incorporated in the formulations, which then become reactive topical skin protectants (rTSPs). Specific and fast screening methods are necessary to assess the decontaminating activity of rTSPs. A headspace sampling technique in conjunction with thermal desorption and gas chromatography-mass spectrometry was evaluated as a potential screening method. A lower detection limit of 1 ng and a coefficient of variation of <20% were observed for the repetitive measurements of residual HD. Using this method, we evaluated a candidate rTSP. The percentage recovery of HD applied to the rTSP decreased by 35% over a 20-min time period compared with a non-rTSP. The candidate formulation showed an instant decontamination of the HD simulant dibutyl sulfide (decontamination was achieved in 2 s). The instrument set-up has the potential to accommodate multiple samples and can be automated. The method can be extended also to test reactive dermal formulations with toxic organophosphorus compounds.

Administration, Topical↗
PubMed1999

Experimental melanin-induced uveitis in the Fischer 344 rat is inhibited by anti-CD4 monoclonal antibody, but not by mannose-6-phosphate.

Experimental melanin-induced uveitis (EMIU) is a rodent model of acute anterior uveitis which was described in 1993. We investigated strain susceptibility, and age and gender characteristics of the model, undertook histological and immunohistochemical studies to investigate underlying cellular mechanisms, and examined several treatment options. Rats were immunized with bovine ocular melanin (250 microg), and disease was followed by slit lamp examination. Lewis, Fischer 344 and Porton rats were found to be susceptible to EMIU, whereas Wistar-Furth, DA, and Hooded Wistar strains were resistant. EMIU was neither age- nor gender-dependent. In Fischer 344 rats, EMIU was characterized clinically by florid anterior segment inflammation. Histopathological findings included infiltration of ciliary body and iris with mononuclear cells and neutrophils. Both CD4+ and CD8+ T lymphocytes were prominent. Rats were then treated with intraperitoneal injections of anti-CD4, anti-CD8 or irrelevant isotype-matched MoAb on days -3, 0, 3, 6 and 9 with respect to melanin immunization. Incidence of uveitis was significantly reduced in rats treated with a non-depleting cocktail of anti-CD4 MoAbs (P = 0.007), whereas a depleting anti-CD8 antibody had no effect on the disease. Mannose-6-phosphate inhibits lymphocyte migration in some models of T cell-mediated inflammation. This simple sugar was administered to additional rats via intraperitoneal osmotic pumps for 14 days following disease induction, but did not influence the uveitis. We conclude that EMIU is controlled by CD4+ T cells, and disease may be abrogated by treatment with anti-CD4 MoAbs.

Animals↗
PubMed1999

Blood perfusion hyperaemia in response to graded loading of human heels assessed by laser-Doppler imaging.

Heel pressure ulcers are important clinical, humanitarian and economic problems arising in part from localized blood flow deficits during loading and inadequate flow recovery. Because there are few data available with regard to the intrinsic physiological responses of heel skin to pressure-induced ischaemia, the present study was undertaken to characterize the main features of the post-loading hyperaemic response. Laser-Doppler perfusion imaging was used to measure hyperaemia in 14 vascularly normal women who were subjected to sequential local heel loading with graded magnitudes (30-140 mmHg) and durations (2.5-20 min). Peak heel perfusion produced by local heating to 44 degrees C for 5 min was used as a comparison standard. All heel loads and durations resulted in hyperaemic responses, with the largest increase in peak response occurring between heel loads of 60 and 120 mmHg. During this transition, peak hyperaemia increased from about 32% to 79% of the local maximal microvascular vasodilatory capacity. Recovery times also increased with both load duration and magnitude, with the longest recovery time being about 7.5 min. Hyperaemic responses and recovery times were analytically dependent on the heel load pressure duration product, with evidence of suppression of the peak response at 1500 mmHg min and a levelling off of recovery time at higher pressure durations. These findings serve to characterize normal physiological perfusion responses to pressure-induced ischaemia at an anatomical site prone to pressure ulceration. The results suggest the possibility of a 'critical' heel loading, above which a near-maximum response is elicited and beyond which vasodilatory recovery potential is blunted.

Adult↗
PubMed1999

Stereoscopic display of atomic force microscope images using anaglyph techniques.

This paper describes the use of a standard stereo-pair image display method for presenting the three-dimensional relief information found in atomic force microscope (AFM) images. The method makes use of commercially available image processing software packages. The techniques are illustrated on AFM images of the cuticle structure of a human hair fibre.

Hair↗
PubMed1999

Linear IgA disease.

PURPOSE: A case of linear IgA disease is reported to alert ophthalmologists and physicians to this unusual cause of chronic cicatrizing conjunctivitis. METHODS: Clinical records of a patient suffering from linear IgA disease were reviewed. RESULTS: A 65-year-old woman with a complicated medical history experienced rapidly progressive chronic cicatrizing conjunctivitis leading to corneal perforation. Undiagnosed gingivitis and palatal ulceration had been present for 5 years prior to the onset of ocular symptoms and vitamin C deficiency had followed the consequent dietary restrictions. A diagnosis of linear IgA disease was made on conjunctival biopsy, which demonstrated linear deposits of IgA along the epithelial basement membrane. The perforation was managed successfully with a conjunctival pediculate flap. Control of the inflammation was achieved with systemic prednisolone and cyclophosphamide but at the expense of serious systemic side-effects. CONCLUSIONS: Linear IgA disease causes progressive conjunctival cicatrization in many affected individuals. Although dapsone generally controls the inflammation, heavier systemic immunosuppression was required in this case. Involvement of skin or other mucosal surfaces may become symptomatic before the conjunctivitis, and physicians must be educated to refer patients for ophthalmological review on diagnosis. Conversely, ophthalmologists encountering ocular linear IgA disease should be aware of the possibility of other mucosal involvement requiring physician intervention.

Aged↗
PubMed1999

A comparison of magnetoencephalography, MRI, and V-EEG in patients evaluated for epilepsy surgery.

PURPOSE: To determine the efficacy and relative contribution of several diagnostic methods [ictal and interictal scalp and intracranial EEG, magnetic resonance imaging (MRI), and magnetoencephalography (MEG)] in identifying the epileptogenic zone for resection. METHODS: This was a prospective study using a masked comparison-to-criterion standard. Fifty-eight consecutive patients with refractory partial epilepsy from two university comprehensive epilepsy programs were studied. Patients who were evaluated for and underwent epilepsy surgery were recruited. The main outcome measure was the efficacy of each diagnostic method to identify the resected epileptogenic zone, when referenced to surgical outcome. RESULTS: MEG (52%) was second only to ictal intracranial V-EEG in predicting the epileptogenic zone for the entire group of patients who had an excellent surgical outcome (seizure free or rare seizure). In a subanalysis, for patients who had temporal lobe surgery, this same relation was seen (MEG, 57%, ictal intracranial V-EEG, 62%). With extratemporal resection, ictal (81%) and interictal (75%) intracranial EEG were superior to MEG (44%) in predicting the surgery site in those patients with an excellent outcome. Finally, for all patients who had a good surgical outcome, MEG (52%) was better than ictal (33%) or interictal (45%) scalp VEEG in predicting the site of surgery. CONCLUSIONS: These results indicate that MEG is a very promising diagnostic method and raise the possibility that it may obviate the need for invasive EEG in some cases or reduce the length of scalp EEG evaluation in others.

Adolescent↗
PubMed1999

Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes.

Based on the dominance of cellular senescence over immortality, immortal human cell lines have been assigned to four complementation groups for indefinite division. Human chromosomes carrying senescence genes have been identified, including chromosome 4. We report the cloning and identification of a gene, mortality factor 4 (MORF 4), which induces a senescent-like phenotype in immortal cell lines assigned to complementation group B with concomitant changes in two markers for senescence. MORF 4 is a member of a novel family of genes with transcription factor-like motifs. We present here the sequences of the seven family members, their chromosomal locations, and a partial characterization of the three members that are expressed. Elucidation of the mechanism of action of these genes should enhance our understanding of growth regulation and cellular aging.

Amino Acid Sequence↗
PubMed1999

Surgical management of intractable epilepsy in children with hemophilia.

Intracranial hemorrhage occurs in 2-8% of patients with hemophilia and can result in neurologic sequelae including seizure disorders. There is a paucity of data concerning the surgical treatment of epilepsy in children with hemophilia. We review our experience with 2 children who developed medically refractory seizure disorders. Both children underwent hemispherotomy, at 18 months (case 1) and 13 years of age (case 2), respectively. Perioperative management included continuous factor replacement. Both children tolerated surgical intervention without complications or increased neurologic deficit. Case 2 showed a 90% reduction in seizure frequency, and case 1 is seizure free. Surgical management of intractable epilepsy in children with hemophilia is safe and effective.

Brain↗
PubMed1999

A 13-year experience with epilepsy surgery.

Between 1985 and 1997, 563 therapeutic craniotomies were performed: 311 anterior temporal (ATL) and 158 extramesial temporal (XMT) resections, 67 callosotomies, 20 hemispherectomies and 7 multiple subpial transections. Sixty-seven percent of nonlesional ATL cases were seizure free (SF), and 76% of nonlesional ATL cases < or =18 years old were SF. Seventy-eight percent of lesional ATL cases with complete resection were SF. Seventy-three percent of lesional cases < or =18 were SF. Thirty-seven percent of nonlesional XMT cases were SF. Seventy percent of XMT lesional cases with complete resection were SF, and 82% of lesional XMT cases < or =18 were SF. Of the anterior callosotomy cases, there was a > or =90% decrease in generalized tonic-clonic seizures in 50% of patients, and in tonic seizures, drop attacks, absence and myoclonic seizures in approximately 60-70% of patients. Of 20 hemispherectomies, 65% were SF. Of 7 multiple subpial transections, 29% were SF.

Adult↗
PubMed1999

Precontraction with elevated concentrations of extracellular potassium enables both 5-HT1B and 5-HT2A "silent" receptors in rabbit ear artery.

The present study was conducted to determine the effect of a small (<10%) K+-induced precontraction on the response to vasoconstrictors in the rabbit aorta and ear artery rings. In both tissues, 15 mM K+ shifted the methoxamine concentration response curve (CRC) approximately 2.4-fold to the left. There was no change in the sensitivity of the control and amplified CRCs to the alpha1 adrenoceptor antagonist prazosin (100 nM). In the aorta, the CRC for serotonin was shifted 4.5-fold to the left in the presence of 15 mM K+, and both the control and amplified CRCs were antagonized equally by the 5-HT2A antagonist ketanserin (10 nM). In contrast, 16 and 20 mM K+ caused up to an approximately 60-fold leftward shift of the serotonin CRC in the rabbit ear artery. This effect of 16 mM K+ was not altered by mechanical removal of the endothelium or by in vitro denervation using 6-hydroxydopamine. The K+-amplified CRC was insensitive to 100 nM prazosin at serotonin concentrations below 3 microM, but was significantly antagonized by 10 nM ketanserin, suggesting that 5-HT2A receptors are involved in the K+-amplified response. The 5-HT1B-selective antagonist, GR 127935, did not affect control responses to serotonin, but significantly blocked the K+-amplified response. Furthermore, the combination of ketanserin and GR 127935 produced a significantly greater blockade of the amplified response than either antagonist alone, supporting the conclusion that both 5-HT2A and 5-HT1B receptors mediate the K+-amplified response to serotonin in the rabbit ear artery.

Animals↗
PubMed1999

Young male violent death trends in the general population during the Vietnam era.

Suicide and homicide rates significantly increased throughout the Vietnam War among young American civilian males who constituted the principal manpower pool for the war. Ironically, men who reached military age after the war were at greatest risk. Years of high combat intensity were not associated with higher suicide or homicide rates than years of low combat intensity. Suicide and homicide rates were correlated at .95, suggesting a common source of pathogenesis. No similar trend was found for motor vehicle death. Broad social forces, not the Vietnam War itself, were responsible for the changes in violent mortality trends that we observed among the birth cohorts of men in our study.

Accidents, Traffic↗
PubMed1999

Young female violent death trends in the general population during the Vietnam era.

Five birth cohorts of young women who became age 20 before, during, and after the Vietnam War were selected for this study of motor vehicle accident, suicide, and homicide between ages 13 and 30. Suicide and homicide increased strongly in succeeding years (1953-1986). Motor vehicle accident rates were affected primarily by age. But age, birth cohort membership, and age x cohort interaction significantly affected suicide and homicide rates, with the 19-24-year-old age range most greatly affected. The correlation between suicide and homicide risk (r = .92) was similar to that for young males (r = .95) and suggested a common source of pathogenesis for both genders.

Accidents, Traffic↗
PubMed1998

Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects.

Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the activity of N-9 is nonspecific, suggesting that virucidal levels may produce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both. A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic and histologic changes in the genital tract, and impact on vaginal flora. Genital irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the placebo group. Inflammatory changes were characterized by patchy infiltration of the lamina propria predominantly with CD8+ lymphocytes and macrophages, in the absence of epithelial disruption. A transient reduction in numbers of lactobacilli was observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a standard spermicidal dose was associated with increased irritation, colposcopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to HIV infection to the genital mucosa is unknown but raises concerns about the suitability of N-9 as a microbicide when given in this dose.

Administration, Intravaginal↗
PubMed1998

Isolation and characterisation of a novel sulphate-reducing bacterium of the Desulfovibrio genus.

A novel sulphate-reducing bacterium (Ind 1) was isolated from a biofilm removed from a severely corroded carbon steel structure in a marine environment. Light microscopy observations revealed that cells were Gram-negative, rod shaped and very motile. Partial 16S rRNA gene sequencing and analysis of the fatty acid profile demonstrated a strong similarity between the new species and members from the Desulfovibrio genus. This was confirmed by the results obtained following purification and characterisation of the key proteins involved in the sulphate-reduction pathway. Several metal-containing proteins, such as two periplasmic proteins: hydrogenase and cytochrome c3, and two cytoplasmic proteins: ferredoxin and sulphite reductase, were isolated and purified. The latter proved to be of the desulfoviridin type which is typical of the Desulfovibrio genus. The study of the remaining proteins revealed a high degree of similarity with the homologous proteins isolated from Desulfovibrio gigas. However, the position of the strain within the phylogenetic tree clearly indicates that the bacterium is closely related to Desulfovibrio gabonensis, and these three strains form a separate cluster in the delta subdivision of the Proteobacteria. On the basis of the results obtained, it is suggested that Ind 1 belongs to a new species of the genus Desulfovibrio, and the name Desulfovibrio indonensis is proposed.

Journal Article↗