Showing papers by "Drexel University published in 1995"

Sensorimotor encoding by synchronous neural ensemble activity at multiple levels of the somatosensory system

Abstract: Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

DSM-IV field trial: Obsessive-compulsive disorder.

Abstract: Objective Three issues relevant to revising the DSM-III-R criteria for obsessive-compulsive disorder were examined in a field trial: 1) the requirement that symptoms of obsessive-compulsive disorder be viewed by the patient as excessive or unreasonable, 2) the presence of mental compulsions in addition to behavioral compulsions, and 3) ICD-10 subcategories. Method The authors studied symptom patterns of obsessive-compulsive disorder as well as strength of obsessive belief among 431 patients with obsessive-compulsive disorder at seven hospital outpatient clinics. Two methods of subject selection were used: consecutive entry of everyone who contacted the clinics for evaluation of obsessive-compulsive disorder and entry of patients with obsessive-compulsive disorder who had continuing contact with the clinics since before the field trial and who were still symptomatic. Primary measures were the Yale-Brown Obsessive Compulsive Scale and face-valid questions about fixity of obsessive-compulsive beliefs. Results The large majority of patients were uncertain about whether their obsessive-compulsive symptoms were unreasonable or excessive, and most had both mental and behavioral compulsions. Results on the ICD-10 subcategories were equivocal. Conclusions The present results converge with previous findings to indicate a broad range of insight among patients with obsessive-compulsive disorder. The DSM-III-R requirement for insight should be de-emphasized in DSM-IV, and mental rituals should be included in the definition of compulsions.

Change in rape narratives during exposure therapy for posttraumatic stress disorder

Abstract: This paper presents a coding system developed to explore changes in narratives of rape during therapy for posttraumatic stress disorder (PTSD) involving repeated reliving and recounting of the trauma. Relationships between narrative categories hypothesized to be affected by the treatment and treatment outcome were also examined. As hypothesized, narrative length increased from pre- to post-treatment, percentage of actions and dialogue decreased and percentage of thoughts and feelings increased, particularly thoughts reflecting attempts to organize the trauma memory. Also as expected, increase in organized thoughts was correlated negatively with depression. While indices of fragmentation did not significantly decrease during therapy, the hypothesized correlation between decrease in fragmentation and reduction in trauma-related symptoms was detected.

Arousal, numbing, and intrusion: symptom structure of PTSD following assault.

Abstract: OBJECTIVE: This study investigated hypotheses concerning the importance of symptoms of numbing in posttraumatic stress disorder (PTSD). METHODS: Symptoms of PTSD were assessed in 72 female rape victims and 86 female victims of nonsexual assault approximately 3 months after the crimes occurred. A principal-components factor analysis of subjects' symptoms was then undertaken. RESULTS: The analysis yielded three factors: arousal/avoidance, numbing, and intrusion. These were somewhat different from the symptom clusters in DSM-III-R, since effortful avoidance and numbing symptoms did not load on the same factor. Numbing symptoms appeared to be particularly important in identifying individuals with PTSD. CONCLUSIONS: The results imply that there are two patterns of posttrauma symptoms, one characterizing PTSD and the second characterizing a phobic reaction. Language: en

Schizophrenia and smoking: an epidemiological survey in a state hospital.

Abstract: OBJECTIVE The authors sought to determine whether smoking is related to schizophrenia or neuroleptic treatment. METHOD Cigarette smoking was measured in all patients hospitalized at a state hospital (N = 360) and compared in relation to gender and diagnosis (schizophrenic versus nonschizophrenic). RESULTS The overall frequency of smoking was 79% (N = 284). Male schizophrenic patients had the highest frequency of smoking, followed by male nonschizophrenic patients, female schizophrenic patients, and female nonschizophrenic patients, respectively. Schizophrenia and polydipsia were associated with both smoking and heavy smoking. CONCLUSIONS After correction for other variables, schizophrenia appears to increase the risk of being both a smoker and a heavy smoker. There was a possible association between high doses of neuroleptics and smoking but only for nonschizophrenic patients.

Association of Flavin Adenine Dinucleotide with the Arabidopsis Blue Light Receptor CRY1

Abstract: The arabidopsis thaliana HY4 gene encodes CRY1, a 75-kilodalton flavoprotein mediating blue light-dependent regulation of seedling development. CRY1 is demonstrated here to noncovalently bind stoichiometric amounts of flavin adenine dinucleotide (FAD). The redox properties of FAD bound by CRY1 include an unexpected stability of the neutral radical flavosemiquinone (FADH.). The absorption properties of this flavosemiquinone provide a likely explanation for the additional sensitivity exhibited by CRY1-mediated responses in the green region of the visible spectrum. Despite the sequence homology to microbial DNA photolyases, CRY1 was found to have no detectable photolyase activity.

Evaluation of a brief cognitive-behavioral program for the prevention of chronic PTSD in recent assault victims.

Abstract: The efficacy of a brief prevention program (BP) aimed at arresting the development of chronic PTSD was examined with 10 recent female victims of sexual and nonsexual assault who received 4 sessions of a cognitive-behavioral program shortly after the assault. Their PTSD and depression severity was compared with that of 10 matched recent female assault victims who received repeated assessments of their trauma-related psychopathology (assessment control; AC). The BP program consisted of education about common reactions to assault and cognitive-behavioral procedures. Two months postassault, victims who received the BP program had significantly less severe PTSD symptoms than victims in the control condition; 10% of the former group met criteria for PTSD versus 70% of the latter group. Five and a half months postassault, victims in the BP group were significantly less depressed than victims in the AC group and had significantly less severe reexperiencing symptoms.

Compliance in patients prescribed eyedrops for glaucoma

Abstract: We studied the rate of failure to use eyedrops as prescribed for glaucoma and some of the factors possibly associated with that noncompliance by interviewing 100 patients being followed in a setting emphasizing correct usage. Fifty-nine reported they had not used their eyedrops precisely as prescribed. Factors significantly influencing compliance included daily dose frequency, forgetfulness, inconvenience, and unaffordability. Gender and race were marginally significant factors, with men and blacks reporting somewhat higher rates of missed doses than women and whites. Side effects and age were not significant causes of noncompliance.

Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer.

Abstract: A significant portion of cell scientific literature published is dedicated to describing the cloning, the link to cancer, or the characterization of proteins involved in the progression of the cell cycle. With this abundance of information, the cascading pathways of molecular events that occur in the cell cycle are proving to be exceedingly complicated. Originally, the sole regulator of the fission yeast cells division cycle, cdc2, was thought to also regulate mammalian cell cycles in the same manner. However, mammalian cdc2 has now been joined by seven well-characterized relatives acting at distinct points in the cell cycle. These kinases are activated by larger proteins called cyclins, named with respect to their cyclical expression and degradation. Therefore, the catalytic subunits of these complexes are named cyclin-dependent kinases (cdks). In the event that the cell must stop normal cycling behavior, a number of cdk inhibitors, which have only begun to be characterized, function in inhibiting the kinase ability of cdks, among other nonproliferative acts. The external environment manipulates cellular proliferation and differentiation by stimulating or inhibiting certain signal transduction pathways. However, each component of the cell cycle machinery, as they are the final executors in cell division, has the potential to elicit or to contribute to a neoplastic phenotype. This review focuses on the characterization of each member of the cell cycle protein family and also addresses the potential role each plays in cancer.

A Multicenter, Double-Blind, Placebo-Controlled Trial of Aprotinin for Reducing Blood Loss and the Requirement for Donor-Blood Transfusion in Patients Undergoing Repeat Coronary Artery Bypass Grafting

Abstract: Background Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. Methods and Results Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor–red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P=.001). The number of units of donor R...

The site and stage of anti-DNA B-cell deletion

Abstract: ANTIBODIES to DNA and nucleoproteins are found in sera of individuals with systemic autoimmune disease. In the population (and in the autoimmune mouse strain MRL/lpr) there is a great variety of such antinuclear antibodies, but individuals with systemic lupus erythematosus or single MRL mice express a subset only of the antinuclear specificities found in the population. These observations have been interpreted to mean that these antibodies arise by immunization1. The oligoclonal nature of the autoantibody response and the evidence of selection acting on somatically mutated autoantibodies favour this interpretation2,3. Specific activation of autoantibodies in disease implies either that autoantibodies are regulated in non-diseased individuals or that autoantigen availability is variable. The former has been demonstrated in anti-DNA transgenic mice. In normal mice, transgene-encoded antibodies against double-stranded (ds) DNA are not expressed in serum or on B cells4–6. Here we describe modified anti-dsDNA transgenic mice which allow us to study the site and developmental stage at which such B-cell regulation occurs. This model shows that in normal mice B cells expressing anti-DNA specificity are deleted in the bone marrow at a pre-B to immature B transitional stage.

Muscarinic acetylcholine receptor subtypes mediating urinary bladder contractility and coupling to GTP binding proteins.

Abstract: Activation of muscarinic acetylcholine receptors is primarily responsible for urinary bladder emptying. Because multiple subtypes of muscarinic receptors exist, we wished to characterize those present in bladder and ultimately to attribute function to those that regulate bladder contractility, neurotransmitter release and perhaps other cholinergic functions in this tissue. Although the m2 and m3 subtypes could be immunoprecipitated after solubilization from human, rat, rabbit and guinea pig bladder membranes, the m1, m4 and m5 subtypes could not. The m2:m3 ratio was 9:1 in rat bladder but was only 3:1 in the other species examined. Immunoprecipitation of the m2 subtype correlated with the relative levels of high-affinity agonist binding sites measured by competition of carbachol for [3H]N-methylscopolamine binding or measured directly using [3H]oxotremorine-M. In the presence of agonist, but not antagonist, GTP binding proteins could be immunoprecipitated in concert with the m2 or m3 receptors using anti-receptor antibodies. These proteins were members of the Gi and Gq/11 subfamilies for both the m2 and the m3 receptor subtypes. In spite of the preponderance of the m2 receptor in all species studied, Schild analysis using somewhat selective antagonists showed that the pharmacologically defined m3 receptor mediated contractility in strips of rat and rabbit bladder. Thus acetylcholine activates bladder smooth muscle via the m3 receptor subtype, and subsequent contractility may be transduced by guanine nucleotide binding proteins such as the Gi and Gq/11 subfamilies.

Vocational rehabilitation of drug abusers.

Abstract: Employment has been identified as an important element in the rehabilitation of drug abusers and, together with abstinence from illicit drugs and criminal involvement, is frequently used as a criterion of treatment outcome. The research literature for the last 20 years on variables affecting employment and the vocational rehabilitation of drug abusers is reviewed with an emphasis on (a) the identification of variables influencing the employment of drug abusers and (b) the evaluation results of interventions that have been developed for this purpose. It is concluded that a number of programs have been demonstrated to have had some success in the vocational rehabilitation of drug abusers. Specific recommendations are made concerning both the direction of further research in this area and the application of existing knowledge in current practice.

The Dose-Response Relationship of Tranexamic Acid

Abstract: Background: Prophylactic administration of the autifibrinolytic drug tranexamic acid decreases bleeding and transfusions after cardiac operations. However, the best dose of tranexamic acid for this purpose remains unknown. This study explored the dose-response relationship of tranexamic acid for hemostatic efficacy after cardiac operation. Methods: In prospective, randomized, double-blinded fashion, 148 patients undergoing cardiac operation with extracorporeal circulation were divided into six groups: a placebo group and five groups receiving tranexamic -acid in loading doses before incision (range 2.5 to 40 mg-kg -1 ) and one-tenth the loading dose hourly for 12 h. The mass of blood collected by chest tubes over 12 h represented blood loss. Allogeneic transfusions within 12 h and within 5 d of surgery were tallied. Results: The six groups presented similar demographics. Patients receiving placebo had increased postoperative D-dimer concentration compared to groups receiving tranexamic acid. Patients receiving at least 10 mg-kg -1 tranexamic acid followed by 1 mg-kg -1 -h -1 bled significantly less (365, 344, and 369 g-12 h -1 , respectively, for those three groups) compared with patients who received placebo (552 g, P<0.05). Tranexamic dose did not affect transfusions. Only initial hematocrit affected whether a patient received an allogeneic transfusion within 5 days of operation (odds ratio 2.08 for each 3% absolute decrease in hematocrit). Conclusions: Prophylactic tranexamic acid, 10 mg-kg -1 followed by 1 mg-kg -1 -h -1 , decreases bleeding after extracorporeal circulation. Larger doses do not provide additional hemostatic benefit

Changes in retinal cell fate induced by overexpression of EGF receptor

Abstract: The differentiation of multipotential progenitor cells in the vertebrate retina into photoreceptors, neurons and glial cells is regulated in part by cell-cell signalling. Transforming growth factor (TGF)-alpha is one of the extracellular signals implicated in the control of several aspects of retinal development, including proliferation and cell fate. The way cells interpret pleiotropic signals such as TGF-alpha is influenced by the level of expression of epidermal growth factor receptor (EGF-R) in some cell lines. To address the influence of receptor level on responses of retinal progenitor cells to TGF-alpha, additional copies of EGF-Rs were introduced in vitro and in vivo with a retrovirus. Normally in vitro, low concentrations of TGF-alpha stimulated proliferation whereas high concentrations biased choice of cell fate, inhibiting differentiation into rod photoreceptors while promoting differentiation into Muller glial cells. We report here that introduction of extra EGF-Rs into progenitor cells in vitro reduced the concentration of TGF-alpha required for changes in rod and Muller cell differentiation but did not enhance proliferation. Introduction of extra EGF-Rs in vivo increased the proportion of clones that contained Muller glial cells, suggesting that receptor level is normally limiting. These findings demonstrate that responsiveness to extracellular signals during development can be modulated by the introduction of additional receptors, and suggest that the level of expression of receptors for these signals contributes to the regulation of cell fate.

Melatonin protects neurons from singlet oxygen‐induced apoptosis

Abstract: Singlet oxygen (O2[1Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O2(1Δg). We investigated whether melatonin might reduce the neurotoxic action of O2(lΔg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O2(1Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3-[4,5-di-methylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal-induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in neurodegenerative diseases.

The nature, distribution and causes of traumatic brain injury.

Abstract: The identification and interpretation of brain damage resulting from a non-missile head injury is often not easy with the result that the most obvious structural damage identified postmortem may not be the most important in trying to establish clinicopathological correlations. For example patients with a fracture of the skull, quite severe cerebral contusions or a large intracranial haematoma that is successfully treated can make an uneventful and complete recovery if no other types of brain damage are present. However, not infrequently more subtle forms of pathology are present and ones that can only be identified microscopically. A systematic and pragmatic approach through the autopsy is therefore required and one that recognises the need for tissue to be retained in ways that are appropriate for cellular and molecular studies.

Risk factors for gallbladder cancer. An international collaborative case–control study

Abstract: Background. Gallbladder cancer has an unusual geographic and demographic distribution, suggesting many possible etiologies. Methods. A case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four patients with newly diagnosed, histologically confirmed gallbladder cancer were compared with 126 control subjects without stones and with 264 control subjects with cholelithiasis or choledocholithiasis without cancer. All study subjects underwent abdominal surgery. Study subjects were interviewed regarding demographic characteristics, medical history, family history, diet, and exposure to agents presumed to be risk factors for biliary cancer. Results. Virtually all subjects in Mexico were judged to be mestizos (i.e., persons of mixed ancestry). In contrast, race was a very strong risk factor for gallbladder cancer in Bolivia. Relative to mestizos who spoke neither language, the odds ratio (95% confidence interval [CI]) for cases versus control subjects without stones for those who spoke Aymara well was 15.9 (CI, 1.9–179), whereas it was 1.4 (CI, 0.2–8.2) for those who spoke Quechua well. An increased risk was also noted for elevated maximum body mass index (P = 0.03), family history of gallstones (odds ratio [OR] = 3.6 [CI, 1.3–11.4]), and physician-diagnosed typhoid (OR = 12.7 [CI, 1.5-598]). An increased risk was also seen with elevated maximum body mass index; compared with those with a body mass index less than 24 kg/m2, those with an index of 24–25 kg/m2, 26–28 kg/m2, and greater than 28 kg/m2 had odds ratios of 1.6 (CI, 0.4–7.6), 1.3 (CI, 0.3–5.6), and 2.6 (CI, 0.5–18.6), respectively (asymptotic test for trend, P = 0.03). Finally, a number of associations were noted with certain dietary and cooking habits. Conclusions. Patients with gallbladder cancer differed from control subjects in race, body mass, physician-diagnosed typhoid, and certain dietary patterns. These findings may provide useful clues to the pathogenesis of gallbladder cancer, but given the number of analyses performed, additional cases need to be studied. Cancer 1995:76:1747–56.

Efflux of cellular cholesterol and phospholipid to lipid-free apolipoproteins and class A amphipathic peptides

Abstract: The mechanism(s) by which lipid-free apolipoprotein (apo) AI is able to stimulate efflux of cholesterol and phospholipid from cells in cultures has (have) been examined. This process was found to be enhanced when macrophages were enriched with cholesterol. There were 12- and 4-fold increases in cholesterol and phospholipid efflux, respectively, from cholesterol-enriched mouse macrophages when compared to cells not loaded with cholesterol. This enhancement in cholesterol efflux to lipid-free apo AI from macrophages enriched with cholesterol was found to be controlled by the level of free cholesterol in the cells. When cholesterol-enriched mouse macrophages were exposed to lipid-free apo AI at 20 micrograms/mL (706 nM), there was significant efflux of [14C]cholesterol and [3H]phospholipid (20% +/- 0.5%/24 h and 6% +/- 0.3%/24 h, respectively). In comparison, HDL at equivalent protein concentrations only stimulated 11% and 4% efflux of cholesterol and phospholipid, respectively. Synthetic peptides containing amphipathic helical segments that mimic those present in apo AI were used to examine the structural features of the apoprotein which stimulate lipid efflux. Peptides containing only one (18A) or two (37pA) amphipathic helical segments stimulated as much cholesterol efflux from both mouse macrophages and L-cells as apo AI. The order of efficiency, as assessed by the mass concentration at which half-maximal efflux was reached (EC50), was apo AI > 37pA > 18A, indicating that acceptor efficiency was dependent on the number of amphipathic helical segments per molecule. When the helical content of 18A was increased by neutralizing the charges at the ends of the peptide (Ac-18A-NH2), there was a substantial increase in the efficiency for cholesterol efflux (EC50 18A = 17 micrograms/mL vs Ac-18A-NH2 = 6 micrograms/mL). In contrast, when the amphipathicity of the helix in 18A was decreased by scrambling the amino acid sequence, thereby reducing its lipid affinity, cholesterol and phospholipid efflux were not stimulated. The efficiency with which the peptides stimulated cholesterol efflux was in order of their lipid affinity (37pA > Ac-18A-NH2 > 18A), and this order was similar for phospholipid efflux. The time course of lipid release from mouse macrophages and L-cells indicated that phospholipid appeared in the extracellular medium before cholesterol. These results suggest that the apo AI or peptides first interacted with the cell to form protein/phospholipid complexes, that could then accept cholesterol.

Adrenal Gland Volume in Major Depression Increase During the Depressive Episode and Decrease With Successful Treatment

Abstract: Background: Hyperactivity of the pituitary-adrenocortical axis is the most prominent neuroendocrine abnormality in major depression. It is state-related, returning to normal with resolution of the depressive episode. Adrenal gland enlargement also has been reported in patients with major depression and has been hypothesized as an index of cumulative lifetime depression. However, whether or not adrenal enlargement decreases with successful treatment of depression has not yet been studied, to our knowledge. We, therefore, determined adrenal gland volume in patients with major depression before and after treatment and in matched normal controls, and compared adrenal size with functional indexes of pituitary-adrenocortical activity. Methods: Adrenal volumes were measured by magnetic resonance imaging in nine adult and two-adolescent patients with major depression during their illness and during full remission when medication had been stopped for at least 1 month, and in nine adult and two adolescent normal control subjects individually matched to the patients. Basal, 4 to 7PMplasma corticotropin 1-39 and cortisol levels, and corticotropin 1-39 and cortisol responses to administration of ovine corticorelin and low-dose cosyntropin also were measured. Results: Mean adrenal gland volume was significantly larger, by about 70%, in the patients while depressed than after successful treatment, and it also was significantly larger, again by about 70%, than the mean adrenal gland volume of their matched controls. After treatment, the mean adrenal volume of the patients decreased and was no longer significantly different from that of their controls at baseline. The magnitude of the decrease was significantly positively correlated with the duration of the depressive episode. Basal, late-afternoon plasma corticotropin 1-39 levels were significantly lower in the patients while depressed than in their matched controls, but basal plasma cortisol levels did not differ significantly among the three groups, nor did the corticotropin 1-39 and cortisol responses to corticorelin or the cortisol response to cosyntropin. Correlations between adrenal gland volume and basal corticotropin and cortisol levels, and the corticotropin and cortisol responses to hormone challenge, were not consistently in the expected direction in any of the three groups of subjects. Conclusions: Adrenal gland enlargement occurring during an episode of major depression appears to be state-dependent, in that it reverts to the normal size range during remission after treatment. It thus does not appear to be an index of cumulative lifetime depression. The lack of a discernible relationship between adrenal volume and pituitary-adrenocortical activity remains to be explained and might be related to noncorticotropin influences on the adrenal gland, including other trophic hormones and/or neural mechanisms.