Modulation of septal influences on hippocampal neurons by cholinergic substances

The effects of electrical stimulation of the medial septal area (MS-DB) for the purpose of distinguishing and assessing the cholinergic component of the septohippocampal input were investigated in awake rabbits in chronic experiments. Initial inhibitory effects of a standard duration of 40-140 msec (54%) predominated in the intact rabbits. In animals with chronic basal undercutting of the MS-DB, initial inhibitory reactions predominated absolutely (90%). An increase in the level of endogenous acetylcholine by administration of eserine led to a partial or complete suppression of all effects of stimulation in 78% of the hippocampal neurons of the intact rabbits against the background of intensification of the theta modulation of the activity of hippocampal neurons. Scopolamine removed theta modulation and restored the reactivity of neurons to stimulation of the MS-DB. These influences of cholinergic substances were maintained in the animals with basal undercutting of the MS-DB. It is inferred that the general initial influence of septal input on neurons of the hippocampus is expressed in the suppression of their activity ("reset"), which depends on the noncholinergic (GABAergic) component of the septohippocampal connections. The cholinergic component limits the effectiveness of both extraseptal (brainstem) and primary inhibitory septal influences on hippocampal neurons.     

Influence of diets with qualitatively different carbohydrates on lipid metabolism

Tissue cultures of HeLa cells in Hank's medium suspension, previously mixed with a solution containing reticulocyte polysomes and/or free globin, hemoglobin and blood plasma from bled rabbits, were homogenized, and an electrophoretic pattern of hemoglobin band was obtained from the supernatant; hemoglobin denatures under the tissue culture conditions. HeLa cells show typical hemosomes, identidical to those found in immature erythrocytes of embryos, and adult mammals with hemolytic anemias. When HeLa cell suspensions are mixed with solutions void of anemic blood plasma, or containing normal rabbit blood plasma, anomalous organelles are formed in the cells, and no hemoglobin biosynthesis occurs.     

Uncut Collis-Nissen fundoplication: learning curve and long-term results

BACKGROUND: Between September 1985 and July 1990, the first 100 consecutive patients (50 female and 50 male) undergoing primary uncut Collis-Nissen fundoplication performed by one surgeon were reviewed. METHODS: Median age was 62 years and ranged from 19 to 89 years. Indications for repair included gastroesophageal reflux in 56 patients, obstructive symptoms in 34, and a combination of both in 10. An upper gastrointestinal endoscopy was performed in 99 patients; all were abnormal. Esophagitis was documented in 53 patients, large diaphragmatic hernia in 36, stenosis in 18, "Cameron's erosions" in 17, Barrett's disease in 13, and other findings in 9 patients. An abnormal upper gastrointestinal series was demonstrated in 96 of 97 patients evaluated. Motility studies were performed in 95 patients, and 11 had abnormal peristalsis. All procedures were performed through a left thoracotomy. RESULTS: Complications occurred in 23 patients and included respiratory failure in 6, atrial fibrillation in 3, atelectasis in 3, pneumonia in 2, myocardial infarction in 2, and chylothorax, severe dysphagia, early breakdown of repair, cardiac tamponade, hematuria, spinal headache, and intraoperative perforation by dilator in 1 each. There were 2 postoperative deaths, both cardiac in origin. Median hospitalization was 8 days (range, 6 to 76 days). The first 25 patients had 10 complications (40%) and 2 deaths (8%). The remaining 75 patients had 13 complications (17%) and no deaths (mortality, p = 0.06; morbidity, p = 0.03). Follow-up was complete in all patients for a median of 100 months (range, 3 to 138 months). Eighty-six of the 98 operative survivors are currently alive. At last follow-up, excellent functional results were observed in 58 patients (59%), good in 24 (25%), fair in 8 (8%), poor in 7 (7%), and unknown in 1 (1%). CONCLUSION: We conclude that the uncut Collis-Nissen fundoplication provides good to excellent long-term results in 84% of patients. Operative mortality and morbidity is acceptable but is associated with a learning curve.     

Medicine at the primary care level (optional undergraduate subject at the University of Alicante): 2 years of experience

OBJECTIVE: We want to put on record two years' experience of undergraduate teaching of an optional subject, "Medicine at the Primary Care level". This was given to sixth-year students by Family and Community Medicine specialist doctors within the Department of Medicine. DESIGN AND SETTING: A crossover study carried out at the University of Alicante. PARTICIPANTS: In the first year, 73 out of the 102 students making up the complete course took part (71.6%); and in the second year, 33 out of 93 (35.5%). MEASUREMENTS AND MAIN RESULTS: The methodology employed, the teaching staff and the documents handed out were given high marks by the students in both cases; as were the course contents in the second year. Deficiencies were noted in the presentation of practical hypotheses. In the first course the students criticised the lack of certain points, basically the tackling of the more common chronic pathologies, something which was corrected in the second year. The survey identified students' wishes to spend longer on the subject. CONCLUSIONS: The students valued positively the existence of a theoretical content specific to Primary Care Medicine. In particular, they requested to be taught performance patterns for prevalent pathologies and for seminars to be organised around practical hypotheses.     

Functional interaction of mammalian valyl-tRNA synthetase with elongation factor EF-1alpha in the complex with EF-1H

In mammalian cells valyl-tRNA synthetase (ValRS) forms a high Mr complex with the four subunits of elongation factor EF-1H. The beta, gamma, and delta subunits, that contribute the guanine nucleotide exchange activity of EF-1H, are tightly associated with the NH2-terminal polypeptide extension of valyl-tRNA synthetase. In this study, we have examined the possibility that the functioning of the companion enzyme EF-1alpha could regulate valyl-tRNA synthetase activity. We show here that the addition of EF-1alpha and GTP in excess in the aminoacylation mixture is accompanied by a 2-fold stimulation of valyl-tRNAVal synthesis catalyzed by the valyl-tRNA synthetase component of the ValRS.EF-1H complex. This effect is not observed in the presence of EF-1alpha and GDP or EF-Tu.GTP and requires association of valyl-tRNA synthetase within the ValRS.EF-1H complex. Since valyl-tRNA synthetase and elongation factor EF-1alpha catalyze two consecutive steps of the in vivo tRNA cycle, aminoacylation and formation of the ternary complex EF-1alpha.GTP. Val-tRNAVal that serves as a vector of tRNA from the synthetase to the ribosome, the data suggest a coordinate regulation of these two successive reactions. The EF-1alpha.GTP-dependent stimulation of valyl-tRNA synthetase activity provides further evidence for tRNA channeling during protein synthesis in mammalian cells.     

The nature of the changes in the immunity of the women who worked in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station and were evacuated from the radioactively contaminated area

During examination of 37 women taking part in elimination of consequences of Chernobyl's disaster was revealed, that complex of disaster factors action resulted the formation of disbalance in the system of immunocompetence cells and caused the oppression of functional activity of neutrophils. In 110 women living on the radioactive contaminated zone (5-40 Ci/km) the phenomena of the secondary immunodeficiency in the form of defeat as cellular as humoral factors of immunity and nonspecific resistance system was diagnosed.     

The observation of chaperone-ligand noncovalent complexes with electrospray ionization mass spectrometry

Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) was applied for the study of noncovalent chaperone SecB-ligand complexes produced in solution and examined in the gas phase with the aid of electrospray ionization (ESI). Since chaperone proteins are believed to recognize and bind only with ligands with nonnative tertiary structure, this work required careful unfolding of the ligand and subsequent reaction with the intact chaperone (the noncovalent tetrameric protein, SecB). A high denaturant concentration was employed to produce nonnative structures of the OppA, and microdialysis of the resulting solutions containing the chaperone-ligand complexes was carried out to rapidly remove the denaturant prior to analysis. Multistage mass spectrometry was essential to the successful study of these complexes since the initial mass spectra indicated extensive adduction that precluded mass measurements, even after microdialysis. However, low energy collisional activation of the ions in the FTICR trap proved useful for adduct removal, and careful control of excitation level preserved the intact complexes of interest, revealing a 1:1 SecB:OppA stoichiometry. To our knowledge, these results present the first direct observation of chaperone-ligand noncovalent complexes and the highest molecular weight heterogeneous noncovalent complex observed to date by mass spectrometry. Furthermore, these results highlight the capabilities of FTICR for the study of such complex systems, and the development of a greater understanding of chaperone interactions in protein export.     

Determination of the binding frame of the chaperone SecB within the physiological ligand oligopeptide-binding protein

Chaperone proteins demonstrate the paradoxical ability to bind ligands rapidly and with high affinity but with no apparent sequence specificity. To learn more about this singular property, we have mapped the binding frame of the chaperone SecB from E. coli on the oligopeptide-binding protein. Similar studies performed on the maltose-binding and galactose-binding proteins revealed centrally positioned binding frames of approximately 160 aminoacyl residues. The work described here shows that OppA, which is significantly longer than the previously studied ligands, has a binding frame that covers 460 amino acids, nearly the entire length of the protein. We propose modes of binding to account for the data.