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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 811 records · Page 45Linked to original sources

A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells.

Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion.

Cyclosporins↗

Meakin adjuvant regimen in premenopausal patients with breast cancer.

A 10-year experience using ovarian ablation and prednisolone as adjuvant therapy for premenopausal patients with breast carcinoma, emphasizing tolerability and morbidity is reported. Thirty patients (15 aged less than 45 years, 15 aged greater than or equal to 45 years; range 28-54 years) underwent mastectomy/lumpectomy with axillary clearance (with or without local irradiation) followed by ovarian irradiation and prednisolone therapy (2.5 mg three times daily for 5 years). Patients were reviewed every 3 months for the first 3 years and every 6 months thereafter. Follow-up was between 1.5 and 10 years (median 5 years). Twenty-four patients are still alive. Three patients stopped therapy because of side-effects. There was a mean(s.e.m.) weight gain of 8.46(1.69) per cent on therapy. Nineteen patients have been weaned off prednisolone over a period of 0.5-7.5 months (median 2 months) and the median length of time off steroids is now 3 years (range 0.5-5 years). This regimen appears to be associated with an acceptable level of patient tolerability and a low chronic morbidity rate and should be considered as an alternative to adjuvant systemic cytotoxic therapy.

Adult↗

An enzyme-linked immunosorbent assay for the detection of antitetanus toxoid antibody using aluminum-absorbed coating antigen.

An enzyme-linked immunosorbent assay (ELISA) for the detection of antitetanus antibodies was developed using aluminum-absorbed tetanus toxoid as the coating antigen. The assay was tested by measuring antitetanus antibody levels in serum obtained from subjects before and after immunization with the aluminum-absorbed tetanus suspension. The specificity of the antibodies for tetanus antigen was tested both before and after antitetanus activity was removed with tetanus antigen-coated beads. Also, the activities of the sera were compared with those of a commercially available test. Our results indicated that the aluminum-absorbed tetanus suspension can be coated onto standard polystyrene ELISA plates and used to measure antibody titers to tetanus toxoid.

Absorption↗

Time-lapse analysis and normal stages of development of cleavage and blastocyst formation in the marsupials the brown antechinus and the stripe-faced dunnart.

The first six normal stages of cleavage and blastocyst formation in vitro of the brown antechinus and the stripe-faced dunnart are described based on 429 embryos from 37 dunnarts and 143 embryos from 32 antechinus and an information from previous studies. Embryos were cultured in Dulbecco's modified Eagle's medium with high glucose and 10% foetal calf serum at 35 degrees C and 5% CO2 in air. Seven antechinus and 18 dunnart embryos were cultured in Rose chambers and filmed by time-lapse cinematography, with an exposure of 0.2 sec and at a rate of 1 frame/30 sec. A rim of zona was formed around the yolk mass during early cleavage. Blastomeres attached to this rim, ensuring that the zona in the hemisphere containing the yolk mass was the first to be lined by blastomeres during blastocyst formation, which is completed at about the 32-cell stage. Two foci were established during cleavage. The descendants of the first cell to divide at the four-cell stage included, at both the fourth and fifth division, the first cell to divide and the cell with the shortest cell cycle time and had the shortest average cell cycle time at each division. The descendants of the cell opposite the first cell to divide at the four-cell stage included, at both the fourth and fifth divisions, the last cell to divide and the cell with the longest cell cycle time and had the longest average cell cycle time at each division.

Animals↗

Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion.

Two metabolically distinct cell populations were detected when two peaks of inorganic phosphate (Pi), corresponding to two pHi values, were recorded by Phosphorus Magnetic Resonance Spectroscopy (31P MRS). One cell population, having intracellular pH (pHi) values less than 6.3, was thought to contain neither PCr (phosphocreatine) nor ATP and was thus considered metabolically unstable or inactive. The second cell population, having normal or near normal pHi, was considered metabolically active with adequate values of ATP and PCr. We can therefore further analyze the bioenergetics in this cell population. The results were based upon studies of 14 ischemic dogs that were anesthetized with 2% isoflurane and ventilated. The amount of Pi associated with the acidic cell population (low pHi) was used to calculate the fraction of metabolically inactive brain tissues. This value correlated well with the ATP depletion of the total cell population. This suggests that in the acidic cell population, PCr and ATP supplies were depleted by dephosphorylation during ischemia, leading to an accumulation of acidic Pi. In addition, ATP synthesis in this population may be inhibited by the low intracellular pH. On the other hand, the bioenergetic state of the metabolically stable cell population having a nearly neutral pHi changed markedly during ischemia. The PCr/Pi dropped to 0.8 and the phosphorylation potential (PP) dropped to 10 mM-1 from 40 mM-1. With reperfusion, two distinct patterns of responses were observed. One group showed the restoration of ATP (recovery group) whereas the second group did not (non-recovery group). After 3 h of reperfusion, the ATP restored group showed complete recovery of PCr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The novel 21-aminosteroid U-74006F attenuates cerebral oedema and improves survival after brain injury in the rat.

The present study evaluated the effect of the non-glucocorticoid 21-aminosteroid U74006F on the development of regional cerebral oedema after lateral fluid-percussion (FP) brain injury in the rat. Male Sprague-Dawley rats (n = 20) were anaesthetized and subjected to lateral FP brain injury of moderate severity (2.5-2.6 atmospheres). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 11) followed by a second bolus (3 mg/kg) at 3 hours vs buffered saline vehicle (equal volume, n = 9). At 48 hours postinjury, animals were sacrificed and brains tissue assayed for water content using wet weight/dry weight methodology. Administration of U74006F significantly attenuated the increase in water content observed in control animals in the ipsilateral hippocampus (adjacent to the site of maximal injury, p less than 0.05). Administration of U74006F also significantly reduced post-injury mortality from 28% in control animals to zero in treated animals (p less than 0.001). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.

Animals↗

Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis.

This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. delta 9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by delta 9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca(++)-dependence of delta 9-THC's action. Augmentation of DA efflux by delta 9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana's rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.

Animals↗

Acoustic technique for determining timing of velopharyngeal closure in swallowing.

A pure tone sound source was introduced at a nostril and monitored by a miniature accelerometer on the throat. During velopharyngeal closure in a swallow, the pure tone component in the accelerometer signal was attenuated. Throat accelerometer recordings were made simultaneously with videofluoroscopy of a modified barium swallow in adults with normal velopharyngeal mechanisms. It was verified that the period of sound attenuation corresponded to the period of velar closure. This noninvasive method of monitoring otherwise silent velopharyngeal closure holds promise for normative studies on swallowing function, as an adjunct method in longitudinal assessment, and as a training aid.

Adult↗

Enhancement of fantasy-induced sexual arousal in men through training in sexual imagery.

Men who in earlier experiments in the same laboratory had been unable to enhance penile tumescence to any substantial degree by engaging in erotic fantasy were given two sessions of either sexual imagery training or general imagery training. Participants in the sexual imagery training program subsequently demonstrated increased physiological and subjective sexual arousal during unstructured as well as structured sexual fantasy. The gains were undiminished at follow-up, 1 month after the end of training. In contrast, general imagery training did not enhance fantasy-induced sexual arousal. Both training programs improved vividness of imagery, as assessed by the Betts QMI Scale, but only sexual imagery training led subjects to report that they were able to form sexual images with higher clarity when engaging in fantasy. Sexual arousal was thus enhanced through context-specific imagery training, a strategy commonly used in the clinical practice of sex therapy.

Adult↗

The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus.

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Amphotericin B↗

Epinephrine-induced vasospasm reversed by phentolamine digital block.

A case of profound digital vasoconstriction caused by the accidental injection of epinephrine from a commercial bee sting kit is reported. One hour later the patient had a cold, painful, blanched finger. A digital block using a 2-mg dose of phentolamine mixed with 2% lidocaine was performed. Thirty minutes after treatment, the finger was pink and warm. The patient reported a marked decrease in pain. Reexamination 12 hours later showed only mild tenderness at the fingertip. No tissue necrosis occurred. One month after injection, there were no apparent sequelae. Although the use of alpha-adrenergic blocking agents by regional infiltration to treat accidental infusion or extravasation of epinephrine has been suggested, no reports of this technique are found in the emergency medicine literature. The mechanism of digital vasoconstriction and the action of phentolamine are discussed.

Accidents↗

Clinical spectrum of leber's congenital amaurosis in the second to fourth decades of life.

Leber's congenital amaurosis is a type of congenital retinitis pigmentosa in which the fundus abnormalities are extremely variable and to some extent age dependent. Most cases are seen in infancy. The retinal, electroretinogram, and fluorescein angiographic findings are described in ten patients with Leber's congenital amaurosis who ranged in age from 13 to 36 years when first seen. All of the patients were from Honduras and were unrelated except for one pair (a brother and sister). The polymorphic appearance of the fundus is emphasized and is particularly striking in the siblings. A macular lesion (a bull's-eye maculopathy) not previously associated with Leber's congenital amaurosis is reported as a variant fundus appearance in this entity.

Adolescent↗

Benign mesenchymoma of the round ligament. A report of two cases with immunohistochemistry.

Benign mesenchymomas are tumors composed of an admixture of two or more mature mesenchymal tissue types. Clinically and histologically they are benign lesions. However, they are seldom encapsulated and therefore may recur locally if incompletely excised. The authors report on two benign mesenchymomas composed of mature fat, thin-walled small and medium size vessels, and spindle cells demonstrated to be smooth muscle by immunohistochemical studies. They were diagnosed in women in their 50s. Both were located in the round ligament of the uterus. One was discovered incidentally during hysterectomy, and the other was unusually large, being diagnosed preoperatively as a retroperitoneal liposarcoma. Most round ligament tumors are leiomyomas or fibromas. To the authors' knowledge, this is the first report of benign mesenchymomas occurring in this location.

Adnexa Uteri↗

Effects of enflurane and isoflurane in air-oxygen on changes in thermal balance during and after surgery.

The temperatures in the aural canal (core), skeletal muscle and skin surface were measured during anaesthesia and surgery in 32 healthy females undergoing total abdominal hysterectomy and for 4 h after operation. The patients were allocated randomly to one of four groups according to the end-tidal concentration of volatile anaesthetic: 1 MAC isoflurane, 1 MAC enflurane, 1.8 MAC isoflurane and 1.8 MAC enflurane. The lungs were ventilated with an air-oxygen mixture. Neuromuscular block was produced with pancuronium. Room temperature and i.v. fluid administration were standardized. Aural canal, muscle and mean skin temperatures decreased significantly in all groups during surgery (P less than 0.001). The decrease in core and muscle temperatures, and mean body heat was significantly greater in the 1.8 MAC groups than in the 1 MAC groups for both volatile agents (P less than 0.001). However, there was a significantly greater decrease in core temperature and mean body heat in the isoflurane compared with the enflurane group (P less than 0.026). Body temperature returned to preoperative values during the recovery period. There was a significantly greater rate of rewarming during the first 1 h of recovery in the 1.8 MAC groups compared with the 1 MAC equivalent (P less than 0.001), and this was independent of the volatile agent used. The present results are compared with those reported previously in which nitrous oxide was added to the volatile agents. The decrease in body temperature depends upon the concentration of vapour used. However, it appears that isoflurane, without nitrous oxide, caused greater loss of body heat than enflurane.

Adult↗