Theory of semiballistic wave propagation.
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Biomedical subjects
Publications and source records attributed to C Barnes.
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Stimulus-linked RNA and protein synthesis is required for establishment of long-term neuroplasticity. To identify molecular mechanisms underlying long-term neuroplasticity, we have used differential cDNA techniques to clone a novel immediate-early gene (IEG) that is rapidly induced in neurons of the hippocampus and cortex by physiological synaptic activity. Analysis of the deduced amino acid sequence indicates homology to members of the pentraxin family of secreted lectins that include C-reactive protein and serum amyloid P component. Regions of homology include an 8 amino acid "pentraxin signature" sequence and a characteristic pentraxin calcium-binding domain. We have termed this gene and the encoded protein Narp (from neuronal activity-regulated pentraxin). Biochemical analyses confirm the presence of a functional signal sequence, and Narp is secreted by transfected COS-1 cells in culture. Additionally, Narp binds to agar matrix in a calcium-dependent manner consistent with the lectin properties of the pentraxin family. When cocultured with Narp-secreting COS-1 cells, neurons of cortical explants exhibit enhanced growth of neuronal dendritic processes. Neurite outgrowth-promoting activity is also observed using partially purified Narp and can be specifically immunodepleted, demonstrating that Narp is the active principle. Narp is fully active at a concentration of approximately 40 ng/ml, indicating a potency similar to known peptide growth factors. Because Narp is rapidly regulated by neuronal activity, its lectin and growth-promoting activities are likely to play role in the modification of cellular properties that underlie long-term plasticity.
The Multi-Link coronary stent (Advanced Cardiovascular Systems, Santa Clara, CA) is a balloon expandable stent carved from a stainless steel cylinder and is composed of 12 corrugated rings connected by multiple links. This design gives the stent great flexibility and conformity as well as radial strength. For the 3 month period from November 1995 to January 1996, all patients undergoing stent implantation in our institution were treated with this device, except for vessels smaller than 2.7 mm or larger than 3.7 mm in diameter, left main disease, or those who could not tolerate anticoagulation therapy. Forty patients, with a total of 42 arteries or 44 lesions, were treated with 56 stents, or 1.33 stents per artery. Clinical presentation included stable angina in 13 (32.5%), unstable angina in 24 (60%), acute myocardial infarction in 2 (5%), of whom 1 was in cardiogenic shock, and atypical symptoms with an abnormal thallium stress test in 1 (2.5%). According to the American College of Cardiology/ American Heart Association (ACC/AHA) classification, 8 lesions (18%) were type A, 14 (32%) type B1, 11 (25%) type B2, and 11 (25%) type C. Forty-three lesions (97.7%) were de novo and 1 (2.3%) restenotic. Stent delivery was successful in all patients. Complications included 1 balloon rupture at 7 atm but without sequelae, and 2 patients in whom the coronary guide wire became kinked and locked inside the catheter shaft of the stent delivery system but stent delivery was eventually successful. Mean diameter stenosis was reduced from 76 +/- 13% presenting to 2 +/- 9% poststenting and minimal lumen diameter increased from 0.87 +/- 0.38 to 2.82 +/- 0.34 mm. There were no acute-subacute stent thromboses, bleeding/vascular complications, or major cardiac events such as myocardial infarction, coronary artery bypass surgery, or death during a follow-up period of 2-5 months (mean 3.6 months). In conclusion, our early clinical experience with the Multi-Link stent is very encouraging, with a very high rate of successful delivery and minimal complications.
We have proposed that endogenous opioids play a critical role in the etiology of anorexia nervosa by mediating an auto-addiction. A biological predisposition may result from an atypical endogenous opioid system. Morphine activation of the system increases food intake in most species, including normal humans and rats, but decreases food intake in mice. The atypical opioid system in mice may be representative of that in anorexia nervosa patients, causing the biological predisposition. Anorexia nervosa is 10 times more prevalent in females than males. In the context of this auto-addiction opioid model, it was interesting to determine if the effects of morphine on food intake were markedly different between the two sexes. Full dose-response curves were done of the effects of morphine on food intake in males and females in both rats and mice, representing the typical and atypical responses, respectively. Differences between the sexes were not found to explain the marked prevalence of anorexia nervosa for females. The marked preference is probably at some other step.
INTRODUCTION: A comparative evaluation of four air samplers was performed using bioaerosol collection in the outdoor environment. METHODS: Test samplers used included a Rotorod, a Kramer-Collins suction trap, an all-glass impinger (AGI-30), and a high-volume cyclonic liquid impinger (SpinCon). All samples were analyzed microscopically for spores and pollen. The two collectors providing a liquid sample (AGI-30 and SpinCon) also were analyzed for specific allergen content by enzyme-linked immunoassay. RESULTS: The SpinCon collected a larger number of spores than the other devices. The number of spores collected by this unit per volume of air sampled was comparable to the AGI-30. The Rotorod and Kramer-Collins collected a lower number of spores per unit of air but collected a larger number of pollen grains per volume sampled. Alternaria allergens Alt a I and GP70 were collected by both liquid impingers; however, the SpinCon collected more Alt a I and the AGI-30 collected more GP70. CONCLUSIONS: The SpinCon is a device that is capable of efficiently sampling a high volume of air and concentrating it in a form that can be analyzed for the presence of spores and fungal allergens. It is less useful for collecting intact pollen grains. Pollen allergen quantitation has not yet been performed on the SpinCon effluent.
AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.
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The International Study Group (ISG) for Behçet's disease proposed new international criteria for Behçet's disease in 1990. The aim of this study was to assess the performance of these criteria in new patient groups. Sensitivity was determined in 300 patients with Behçet's disease from seven countries, and specificity in a group of 62 control patients from China. The ISG criteria performed well compared to the other criteria sets in current use.
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In order to study the pattern of male fertility in Noonan syndrome, and its potential implications for genetic counselling, the genital tract function was studied in 11 adult males with Noonan syndrome. Bilateral testicular maldescent occurred in six. The mean testicular volume was 21 (SD 4) ml. The stretched flaccid penile length was 11.4 (SD 1.2) cm. Puberty was delayed in three. Four of the men had fathered children. The LH and testosterone levels were essentially normal in all men, while the FSH levels were grossly raised in the group with testicular maldescent, with the exception of one man. Semen samples were obtained from five men, and azoospermia or oligozoospermia was present in four of them. Sexual function is not affected in men with Noonan syndrome, but the onset of sexual activity was delayed in men with late onset of puberty. Bilateral testicular maldescent appears to be the main factor contributing to impairment of fertility in men with Noonan syndrome.
Using high-performance thin-layer chromatography, we identified GM1, GM3, GD3, GD1a, GT1b, GQ1b, and other gangliosides in chinchilla cochlea and cerebellum. GM1 was also identified on chromatograms with the B-subunit of cholera toxin (BCT). BCT was also used to determine the distribution of GM1 in fixed and unfixed tissues from cochlea, cerebellum, and sciatic nerve. Positive control tissues showed expected labeling of GM1 by BCT. Negative controls showed expected suppression of BCT binding to GM1 after GM1 extraction and GM1 absorption. In the cochlea, GM1 appeared abundant in plasma membranes of most epithelial cells lining the endolymphatic surface of the scala media, including the interdental, inner supporting, pillar, Deiters, Hensen, Claudius, Boettcher, spiral prominence, and external sulcus. GM1 appeared less abundant in cells of the stria vascularis, Reissner's membrane, and in nerve fibers. In hair cells, the stereocilia appeared to contain GM1; however, the endolymphatic surface of the cuticular plate and the body of the outer hair cells appeared to contain little GM1. In addition, the tectorial membrane, connective tissue of the spiral limbus, and amorphous layer of the basilar membrane also appeared to contain little GM1. Enzymatic degradation of glycoproteins and transformation of polysialogangliosides to GM1 increased the reactivity of BCT to cochlear GM1. This further supported the presence of GM1 and other gangliosides in the cochlea. Although the functional significance of GM1 and other gangliosides in the cochlea is not yet known, they are likely to play important roles in membrane function.
BACKGROUND: Rush immunotherapy, while having many potential benefits, is associated with an increased incidence of systemic reactions. OBJECTIVE: To determine whether pretreatment with medications reduces the rate of systemic reactions during rush immunotherapy and to identify predictors of such reactions if possible. METHODS: We conducted a double-blind, placebo-controlled study of 22 allergic children ages 6 to 18 years who received rush immunotherapy. Active treatment consisted of a combination of H1 and H2 histamine antagonists and a corticosteroid in gelatin capsules given prior to administration of rush immunotherapy whereas placebo patients received lactose. Rush immunotherapy consisted of eight injections of increasing doses of a mixture of allergens to which each patient was skin-reactive over 1 1/2 days. Serial skin tests and peak expiratory flow rate measurements were performed during the procedure. Following the initial series of injections, patients were followed for 8 weeks and had blood drawn at 2-week intervals for measurements of specific IgG and IgE. RESULTS: Systemic reactions were observed in 3 (27%) active and 8 (73%) placebo patients (Fisher's exact test: P = .047). The mean time for systemic reactions was 63 minutes after a previous injection. The most common dose causing a systemic reaction was 0.3 mL of 1:1000 (wt/vol). The best predictors of development of a systemic reaction were degrees of skin sensitivity to the extract before and after premedication. Local reactions were not associated with subsequent systemic reactions. Specific IgG rose by 2 weeks while specific IgE did not change significantly during the 8-week follow-up period. Pretreatment did not change the number of systemic reactions seen with subsequent injections. CONCLUSIONS: Premedication significantly reduces the incidence of systemic reactions during rush immunotherapy and is therefore recommended. Degree of skin sensitivity to the injected extract may eventually prove to be a clinically useful predictor for the development of systemic reactions.
Apolipoprotein B mRNA editing involves the conversion of a cytidine at nucleotide 6666 to a uridine, thereby creating a translational stop codon from a glutamine codon. Recent evidence suggest that a cytidine deaminase is responsible for catalyzing the C to U conversion. All known nucleotide deaminases require zinc as part of their catalytic domain. Utilizing the selective chelator for zinc, 1,10-penanthroline, we demonstrate that in vitro editing activity in rat liver extracts is zinc dependent. These data, taken together with recent reports, strongly support a role for a cytidine deaminase and nucleotide conversion as the catalytic mechanism for apoB mRNA editing.
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Fetal loss through miscarriage or termination of pregnancy for genetic reasons often provokes the grief of bereavement. This is not fully understood, and the extent of the distress is often underestimated by professionals and family alike. We have examined elements of the normal bereavement process and have found that they may occur in specific and accentuated forms in mid-trimester fetal loss. We discuss our findings in the light of the attachment theory--a psychodynamic model for understanding grief reactions.