Barrels VI: Proceedings of a satellite symposium of the 1994 Society for Neuroscience Meeting

Recent neurophysiological studies have revealed the patterns of neuronal activity during the acquisition of goal-directed behaviors, both in single cells, and in large populations of neurons. We propose a model which helps three sets of experimental results in the monkey to be understood: (1) activity of single cells vary greatly and only population activities are causally related to behavior. The model shows how a population of stochastic neurons, whose behaviors vary widely, can learn a skilled conditioned movement with only local activity-dependent synaptic changes. (2) typical changes in neuronal activity occur when the rules governing the behavior are changed, i.e. when the relationship between cues and actions to reach a goal changes over time. There are two types of neuronal patterns during changes in reward contingency: a monotonic increasing pattern and a non-monotonic pattern which follows the change in the way the reward is obtained. Units in the model display these two types of change, which correspond to synaptic modifications related to the encoding of the behavioral significance of sensory and motor events. (3) These two patterns of neuronal activity define two populations whose anatomical distributions in the frontal lobe overlap with a gradient organized in the rostro-caudal direction. The model consists of two artificial neural networks, defined by the same set of equations, but which differ in the values of two parameters (P and Q). P defines the adaptive properties of processing units and Q describes the coding of information. The model suggests that a balance in the relative strengths of these parameters distributed along a rostro-caudal gradient can explain the distribution of neuronal types in the frontal lobe of the monkey.     

Pathology of the eye in sarcoidosis

Comprehensive neurologic and ophthalmologic examinations of 100 patients with morphologically verified sarcoidosis showed the most frequent involvement of optic nerves and less incident lesions of the eye proper and its appendages. Vision disorders were detected in 39.0 patients, chiasmal disorders in 12.0%. Fundus oculi abnormalities were found in 27.0% of patients. A specific feature of vision disorders in sarcoidosis was that almost half of the patients did not feel them, which may be explained by a predominantly chronic latent pattern of these disorders and by the fact that, despite manifest disorders of peripheral vision, central vision with correction remained normal for a longer time.     

Evidence for an age-related dysfunction in the antiproliferative response to transforming growth factor-beta in vascular smooth muscle cells

The p34cdc2 protein kinase plays a key role in the control of the mitotic cell cycle of fission yeast, being required for both entry into S-phase and for entry into mitosis in the mitotic cell cycle, as well as for the initiation of the second meiotic nuclear division. In recent years, structural and functional homologues of p34cdc2, as well as several of the proteins that interact with and regulate p34cdc2 function in fission yeast, have been identified in a wide range of higher eukaryotic cell types, suggesting that the control mechanisms uncovered in this simple eukaryote are likely to be well conserved across evolution. Here we describe the construction and characterisation of a fission yeast strain in which the endogenous p34cdc2 protein is entirely absent and is replaced by its human functional homologue p34CDC2. We have used this strain to analyse aspects of the function of the human p34CDC2 protein genetically. We show that the function of the human p34CDC2 protein in fission yeast cells is dependent upon the action of the protein tyrosine phosphatase p80cdc25, that it responds to altered levels of both the mitotic inhibitor p107wee1 and the p34cdc2-binding protein p13suc1, and is lethal in combination with the mutant B-type cyclin p56cdc13-117. In addition, we demonstrate that the human p34CDC2 protein is proficient for fission yeast meiosis, and examine the behaviour of two mutant p34CDC2 proteins in fission yeast.     

Effects of calcium channel entry blockers on cocaine and amphetamine-induced motor activities and toxicities

The effects of calcium channel entry blockers on cocaine and amphetamine-induced behavioral responses were investigated. Cocaine and amphetamine produced dose-dependent increases in locomotor activity and stereotyped behavior with a maximum response at 40 and 1.2 mg/kg, respectively. The 1,4-dihydropyridine nimodipine and the benzothiazepine diltiazem were more effective in inhibiting cocaine (20 mg/kg)-induced responses than amphetamine (0.6 mg/kg)-induced responses. At doses of cocaine and amphetamine that caused seizures and death, nimodipine, nitrendipine and diltiazem did not offer any protection; rather, they potentiated the toxicities produced by these psychomotor stimulants.     

Fasting does not impair insulin-stimulated glucose uptake but alters intracellular glucose metabolism in conscious rats

Effects of 24-h and 48-h fasting on maximal insulin-stimulated whole-body and muscle glucose uptake, glycogen synthesis, and glycolysis were studied in conscious rats by combining the glucose clamp technique with tracer methods. Fasting decreased body weight and basal plasma glucose, plasma insulin, hepatic glucose output, and glucose clearance (P < 0.05 for all). However, maximal insulin-stimulated whole-body glucose uptake, normalized to body weight, was almost identical in fed, 24-h fasted, and 48-h fasted rats (191 +/- 8, 185 +/- 14, and 182 +/- 5 mumol.kg-1.min-1, respectively; P > 0.7). Similarly, rates of insulin-stimulated glucose uptake by four different skeletal muscles, estimated by the 2-deoxyglucose injection technique, were not different among the three groups. In contrast to glucose uptake, insulin-stimulated whole-body glycolysis was decreased significantly after fasting (36% after 48 h fasting; P < 0.05), whereas insulin-stimulated whole-body glycogen synthesis was increased (44% after 48 h fasting; P < 0.05). In fed rats, glycolysis was the major pathway for glucose metabolism during hyperinsulinemia, accounting for 60 +/- 5% of glucose uptake. This fraction was decreased significantly by fasting (P < 0.01), so that after a 48-h fast, glycolysis accounted for only 40 +/- 3% of insulin-stimulated glucose uptake and glycogen synthesis became predominant pathway, accounting for 60 +/- 3% of whole-body glucose utilization. Whole-body patterns of glucose metabolism during hyperinsulinemia were paralleled by glucose metabolism in individual muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effects of cocaine on ornithine decarboxylase activity in fetal and neonatal rat heart: evidence for cardiotoxicity

Fetal exposure to cocaine is associated with increased perinatal cardiac risk. In the current study, we examined the effects of acute cocaine administration on ornithine decarboxylase (ODC) activity in fetal and neonatal rat heart. ODC is a key regulatory enzyme in the control of cell differentiation and growth, and rapid changes in ODC are associated with the response to cell injury. Administration of 30 mg/kg s.c. of cocaine to pregnant rats on the 20th day of gestation caused acute elevation of fetal cardiac ODC that persisted throughout the ensuing 24 h. In contrast, the same dose given directly to neonatal rats the day after birth evoked only a short-term (1-h) stimulation of ODC that was reversed by 4 h after treatment. By 4 days of age and subsequently, cocaine was unable to elicit acute stimulation of heart ODC and only evoked inhibition of enzyme activity. Elevated progesterone levels during pregnancy have been shown to sensitize the maternal myocardium to cocaine-induced catecholaminergic effects; the greater sensitivity of fetal heart ODC to cocaine, as compared to neonatal heart, supports the hypothesis that similar enhancement of fetal cardiac irritability can contribute to cocaine-induced cell damage.     

Incidence of nasal carriers of Staphylococcus aureus in and outside hospital environment and antibiotic sensitivity of isolated staphylococcus strains

This study was carried out on 100 nasal swabs collected from medical personnel (nurses and doctors) and patients inside hospital environment and also from 50 individuals outside hospital. The swabs were inoculated on different culture media for isolation of /staphylococci which were further identified as S. aureus either by classic bacteriologic methods or by one of rapid screening test of S. aureus. The isolated strains were tested for antibiotic sensitivity to some of B-Lactam antibiotics and to other antibiotics. The results showed that significantly higher percentage of coagulase + ve Staph. were isolated from newborn nursery (90%), operating theatre (71.4%) and hemodialysis unit (60%) than those isolated from intensive care unit, cancer chemotherapy, surgery, chest, internal medicine departments (25%, 26.6%, 31.2%, 33.3%, 50%) respectively. It also showed significant difference in isolation rate between persons at the hospital (patients, doctors and nurses) 44% and controls (normal population) 26%. Most isolates of coagulase + ve Staph. were resistant to penicillin G (93.2%), Streptomycin (77.3%), tetracycline (61.4%) and sensitive to cefamandole (95.4%). All coagulase+ve Staph. isolates were resistant to sulphonamide and methicillin and all sensitive to vancomycin.     

Quality of life and pain in patients with recurrent breast and gynecologic cancer

The kinetic mechanisms of the binding to tubulin of colchicine and eight different analogues have been studied to elucidate details of the recognition mechanism. All of the analogues follow a two step binding mechanism i.e. binding occurs via an initial step with low affinity, followed by an isomerisation of the initial complex leading to the final high affinity state. For several analogues the kinetic and thermodynamic data of both processes are compared here. For all the analogues the delta G1 degree of initial binding at 25 degrees C varies between -13.3 and -28.8 kJ. mol-1. For the second step delta G2 degrees varies between -2.4 and -27 kJ. mol-1. These limited ranges of free energy change are, however, obtained by a great variety of enthalpy changes and compensatory entropy changes. Comparison of the data for the first and second steps indicates that structural alterations of the drugs always change the thermodynamic parameters of the two steps, and the changes in the first and the second steps are in opposite directions. The fact that this range of experimental behaviour can be incorporated into a general mechanism encourages the extension of these investigations to other colchicine analogues and related compounds with potential pharmaceutical applications.     

Biochemistry of coenzyme B12-dependent glycerol and diol dehydratases and organization of the encoding genes

Glycerol and diol dehydratases exhibit a subunit composition of alpha 2 beta 2 gamma 2 and contain coenzyme B12 in the base-on form. The dehydratase reaction proceeds via a radical mechanism. The dehydratases are subject to reaction inactivation by the substrate glycerol which is caused by a cessation of the catalytic cycle because coenzyme B12 is not regenerated, instead 5'-deoxyadenosine and a catalytically inactive cobalamin are formed. The genetic organization of the dehydratase genes is quite similar in all organisms. Downstream of the dehydratase genes an open reading frame encoding a polypeptide of approximately 600 amino acids was identified which is apparently involved in the reactivation of suicide-inactivated enzyme.     

Feasibility study of repeated fluorescent in-situ hybridization in the same human blastomeres for preimplantation genetic diagnosis

In order to increase the number of chromosomes examined in each blastomere, we have developed a repeated fluorescent in-situ hybridization (FISH) procedure by which six or more chromosomes can be analysed per blastomere of a human embryo. Three consecutive FISH procedures with directly-labelled fluorescent Vysis DNA probes were carried out for examination of chromosomes X, Y, 11, 13, 18 and 21 in the same blastomeres (n = 126) and lymphocytes (n = 164). Based on the initial number of nuclei, the percentages of nuclear loss and presence of signals were 3 and 92% respectively in blastomeres; 6 and 91% respectively in lymphocytes after the first FISH; 7 and 87% respectively in blastomeres and 10 and 86% respectively in lymphocytes, after the second FISH. These percentages were 13 and 78% respectively in blastomeres and 14 and 81% respectively in lymphocytes after the third FISH. The FISH procedure was repeated successfully in a couple for preimplantation genetic diagnosis of chromosomal aneuploidies in biopsied blastomeres of their embryos in our clinic. In conclusion, it is feasible to carry out repeated FISH procedures in the same blastomeres. Six or more chromosomes of a single blastomere may be examined using this procedure.