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Biomedical subjects

B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Staurosporine impairs both short-term and long-term potentiation in the dentate gyrus in vitro.

The present study shows that the protein kinase inhibitor staurosporine impairs the transient (< 60 min) potentiation (short-term potentiation) evoked by a weak tetanus to about the same extent as the more stable potentiation (long-term potentiation) evoked by a strong tetanus. This effect on short-term and long-term potentiation was seen both as a reduced magnitude and an increased decay rate, the latter being increased by about 50% compared to that seen under normal conditions. Comparison with potentiations evoked at different strengths in control solution suggested that much, but not all, of the increased decay rate observed in the presence of staurosporine could be explained by an impared induction. Staurosporine did not affect the N-methyl-D-aspartate-mediated field excitatory postsynaptic potential evoked by low-frequency stimulation or the magnitude of N-methyl-D-aspartate-mediated currents during high-frequency tetanization. This result suggests that the induction is impaired at a stage not related to the N-methyl-D-aspartate-mediated calcium influx. The present results suggest that short-term and long-term potentiation cannot be separated on the basis of protein kinase dependence. They do not support the common notion that short-term and long-term potentiation are mechanistically separate entities. Instead, the results support the view that long-term potentiation has a variable duration/stability dependent on the induction conditions and that protein kinase activation, via an action on induction mechanisms, contributes to its stabilization.

Alkaloids↗
PubMed1994

Antibody production of a human EBV-transformed B cell line and its heterohybridoma and trioma cell line descendants in different culture systems.

Cells of an EBV-transformed human lymphoblastoid B cell line, producing antibodies directed against tetanus toxin, were fused with mouse myeloma cells (SP2/0) and with mouse-human heteromyeloma cells (SPAM-8) resulting in the formation of heterohybridoma and trioma cells, respectively. Antibody production of the three cell lines were studied under different culture conditions. All three cell lines produced antibodies in concentrations ranging from 2.6 to 6.4 micrograms ml-1 in spent medium from stationary flask cultures. Dialysis cultures of trioma and heterohybridoma cells resulted in concentrations of 36 and 20 micrograms ml-1, respectively, whereas no significant increase was obtained with the EBV-transformed cells. Trioma cells, cultured in a hollow fiber cartridge bioreactor produced antibodies in concentrations of average of 303 micrograms ml-1, whereas the EBV-transformed cells did not adapt to this system. Furthermore, trioma and heterohybridoma cells injected into the intraperitoneal cavity of SCID-mice, produced antibodies in ascites fluid in concentrations of 500 and 640 micrograms ml-1 respectively.

Animals↗
PubMed1994

TEA elicits two distinct potentiations of synaptic transmission in the CA1 region of the hippocampal slice.

Extracellular application of tetraethylammonium (TEA) has been shown to elicit a prolonged synaptic potentiation in the CA1 region of the hippocampus that is unaffected by NMDA receptor antagonists, but is blocked by antagonists to voltage-dependent calcium channels (Aniksztejn and Ben-Ari, 1991; Huang and Malenka, 1993). In the present study the relation between TEA-induced potentiation and NMDA receptor-dependent long-term potentiation (LTP) was investigated in the CA1 region of the hippocampal slice using extracellular recordings and picrotoxin to block GABAA-mediated inhibition. Consistent with the finding of Huang and Malenka (1993), NMDA receptor-dependent LTP partially occluded the TEA-induced potentiation. However, this occlusion was abolished when the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was present during the application of TEA, indicating one component of TEA-induced potentiation that is induced via NMDA receptor channels and another component that is distinct from NMDA receptor-dependent LTP. In the presence of antagonists to voltage-dependent calcium channels (nifedipine or nifedipine/flunarazine) application of TEA induced a potentiation that was largely occluded by NMDA receptor-dependent LTP. In common with NMDA receptor-dependent LTP, the TEA-induced potentiation, elicited in the presence of antagonists to voltage-dependent calcium channels, was associated with a symmetrical increase of the field EPSP. On the other hand, the TEA-induced potentiation elicited in the presence of D-AP5 produced an increase of the field EPSP that did not include the early part of the initial slope.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1994

Effect of adenosine-induced changes in presynaptic release probability on long-term potentiation in the hippocampal CA1 region.

In the present study some characteristics of long-term potentiation (LTP) in the hippocampal CA1 region were examined under different conditions of transmitter release. Adenosine A1 agonist/antagonists, or in some instances changes in the extracellular calcium/magnesium ratio, were used to alter release probability. The overall LTP time course (onset latency, growth phase, and subsequent decay for both the non-NMDA and NMDA receptor-mediated EPSPs) following a brief tetanus was essentially the same over an almost 10-fold variation in release probability (measured as change in field EPSP magnitude). The major difference observed was a faster initial decay of LTP evoked at low levels of release probability, possibly related to impaired induction conditions. It was also observed that LTP induced at one level of release probability occluded that induced at a lower (or higher) level, and that changes in release probability induced by adenosine agonist/antagonists affected potentiated and "naive" EPSPs to an equal extent. Taken together, these data do not provide support for the notion of different locations for LTP expression at different conditions of release probability. The results are also more compatible with the notion of a single, rather than several, expression mechanism(s) within the first hour of LTP in the hippocampal CA1 region.

Adenosine↗
PubMed1994

In the search for a novel class of antipsychotic drugs: preclinical pharmacology of FG5803, a 1-piperazinecarboxamide derivative.

Comparative studies of the 1-piperazinecarboxamide derivative 4-[3-(4-fluorobenzoyl)propyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (FG5803) were made with clozapine and haloperidol. Receptor studies revealed that FG5803 potently and selectively bound to the serotonin type 2A receptors (Ki = 13 nM). FG5803 inhibited 5-hydroxytrophan- and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitches, which indicated potent in vivo serotonin type 2A receptor antagonism. FG5803 caused an acute activation of the tuberoinfundibular dopamine neurons and produced only a transient rise in plasma prolactin. In behavioral studies in rats, FG5803 showed strong antagonistic action on presynaptic dopaminergic autoreceptors but only weak postsynaptic dopamine D2 blockade. FG5803 was not cataleptogenic and did not antagonize amphetamine-induced stereotypies. FG5803 was active in the reduction of aggressive behavior and spontaneous exploratory behavior in mice and rats. Therefore, FG5803 is expected to constitute a promising approach in the search for a novel class of antipsychotic drugs that have a broader spectrum of activity and fewer adverse effects than the conventional, antidopaminergic antipsychotics.

Animals↗
PubMed1993

Neutralization of tetanus toxin by human monoclonal antibodies directed against tetanus toxin fragment C.

Two hybridomas (designated 143 and 147) producing human monoclonal antibodies (IgG1) directed against tetanus toxin were established by fusion of Epstein-Barr virus transformed human peripheral B lymphocytes with the heteromyeloma SPAM-8. The hybridomas produced antibodies in concentrations of approx. 3.5 micrograms/ml (hybridoma 143) and 6.4 micrograms/ml (hybridoma 147) using conventional flask cultures and 33.9 micrograms/ml and 36.2 micrograms/ml, respectively, in dialysis cultures. The antibodies were shown to react with tetanus toxin, toxoid and fragment C in ELISA, and reactivity with tetanus toxin and fragment C was confirmed in SDS-polyacrylamide gel electrophoresis followed by Western blots. The antibody binding sites were located to two different epitopes of fragment C as shown in a competition assay using biotinylated antibodies. Furthermore, binding of both antibodies to fragment C was inhibited by the addition of the receptor-associated ganglioside GT1b. Neutralization of tetanus toxin in concentrations equivalent to 100-120 IU per mg of antibody was observed for both antibodies in a mouse protection assay.

Antibodies, Monoclonal↗
PubMed1993

Mucosal exudation of plasma is a noninjurious intestinal defense mechanism.

We have demonstrated in sensitized rats that the immediate response to endointestinal challenge with allergen (10(-6) M ovalbumin) is characterized by mucosal exudation of plasma with little or no concomitant change in the mucosal absorption capacity. The luminal entry of plasma macromolecules also leaves the light microscopic structure and the ultrastructure of the mucosa unaffected. It is possible that the plasticity of epithelial zonulae occludens allows a noninjurious and unidirectional paracellular flux of extravasated plasma into the gut lumen. We propose that inflammatory-stimulus-induced mucosal exudation of plasma belongs to the first-line defense mechanisms of the intact lining of the intestine.

Allergens↗
PubMed1992

[Memory at the synaptic level].

Ever since the discovery of the synapse at the end of the last century it has been surmised that elementary neural changes underlying learning and memory are located at the junctions between nerve cells. Experimental studies during the past 20 years have demonstrated the existence of several synaptic modification processes, the most prominent being long-term potentiation (LTP) in the hippocampus. Several links between LTP and learning/memory have been established. For example, memory impairment in older rats is well correlated, with increasing decline of LTP, and N-methyl-D-aspartate (NMDA) receptor antagonists give rise to a parallel blockade of LTP and of spatial task learning. Studies on rats in a natural learning situation have also demonstrated 'spontaneous' occurrence of LTP. LTP is induced as a consequence of coincident pre- and post-synaptic activity, and thus in conformity with a basic principle of learning theory known as Hebb's rule. Responsible for this associative induction is the NMDA-subtype of glutamate receptor channel with its unique property of being both transmitter and voltage controlled. Its opening allows calcium ions to enter the postsynaptic cell and to initiate biochemical processes leading to a lasting synaptic modification. The nature of the critical processes involved in establishing the modification(s) is uncertain, although the participation of calcium-activated protein kinases seems likely. There is still considerable controversy whether the actual change occurs postsynaptically, or presynaptically, triggered via a retrograde signal from the postsynaptic cell. LTP similar to that in the hippocampus has recently been described for various neocortical regions.

Animals↗
PubMed1992

Do physicians care about patients with dysphagia? A study on confirming communication.

Thirty-nine patients with longstanding oesophageal dysphagia took part in an interview and a questionnaire study to investigate whether they considered themselves met with interest, respect, understanding and knowledge (felt confirmed) when consulting their physician for the first time (mostly general practitioner), whether non-confirmed patients have any distinguishing attributes, and whether confirmation affects the patient's impression of being helped. Twenty-five of these considered themselves as non-confirmed. There was no difference between the groups as regards sex, age, education, degree of swallowing difficulties and incidence of chest symptoms other than dysphagia. There was a greater fear of cancer (P less than 0.05) and a stronger indirect aggression (P less than 0.05) among the non-confirmed patients. Patients who felt confirmed reported more often that a correct oesophageal diagnosis had been given (P less than 0.05), felt they had received adequate help (P less than 0.001) and experienced improvement in swallowing difficulties (P less than 0.05). It is concluded that patient attributes seem to slightly influence the patients' possibilities of being confirmed, and that confirmation is of great importance for the patient's feeling of being helped and improved.

Adolescent↗
PubMed1992

Allergen-induced mucosal exudation of plasma into rat ileum and its inhibition by budesonide.

Exudation of plasma across the airway mucosa is a specific defence/inflammatory response finely regulated by mediators and (in rodents) a capsaicin-sensitive innervation. This study examines plasma exudation responses to endointestinal challenges and effects of a glucocorticoid. The ileum of anesthetized rats was catheterized and ligated at two points 10 cm apart for mucosal challenge (0.5 ml) and repeated lavages (5 ml). Lavage fluid levels of the plasma tracer 125I-albumin, previously injected intravenously, showed a stable, low base line greater than 2 h. Challenge with mediators (10(-5) M bradykinin, 10(-5)-10(-3) M serotonin, 10(-6)-10(-4) M histamine, 2.10(-9)-2.10(-7) M leukotriene D4 (LTD4), or 10(-5)-10(-3) M capsaicin did not increase luminal radioactivity. However, allergen (10(-6) M ovalbumin, in previously sensitized animals) produced prompt mucosal exudation of 125I-albumin, peaking within 30 min (p less than 0.001) and returning to base line within 90 min. Separate experiments suggested that absorption was not increased during the mucosal exudation. The glucocorticoid budesonide (10-1000 micrograms/kg given by gavage 24 h before challenge) dose-dependently inhibited the allergen-induced exudation (p less than 0.01). The route of administration and the antiexudative versus the systemic potency (reduced thymus weight) suggest the possibility of a topical action of budesonide. We conclude that endointestinal allergen challenge produces reversible and glucocorticoid-inhibitable exudation of plasma across the mucosa. It appears less likely that bradykinin, serotonin, histamine, LTD4, or a capsaicin-sensitive innervation is involved in producing this exudative effect.

Administration, Topical↗
PubMed1992

Postsynaptic, but not presynaptic, activity controls the early time course of long-term potentiation in the dentate gyrus.

The early time course (less than 1 hr) of long-term potentiation (LTP) in the dentate gyrus of the guinea pig hippocampal slice was examined using extracellular recordings from the outer two-thirds of the dendritic layer. LTP was induced by a single brief (2-40 impulses) high-frequency (20-400 Hz) train, or by pairing a single test stimulus with a brief heterosynaptic high-frequency train. The induction of LTP was facilitated by blockade of fast GABAergic postsynaptic inhibition. It was found that, irrespective of induction conditions and the amount of LTP induced, the onset of LTP was characterized by a latency of a few seconds following the induction event, and a rapid 30 sec growth phase. After a 1-2 min period of little or no further growth, LTP decayed but in a highly variable manner, from cases in which more than 60% of the peak value remained 1 hr after the induction to cases in which LTP decayed completely within 10 min. Factors increasing presynaptic activity (frequency or number of afferent stimulations) during the induction event did not affect the relative amount of LTP decay. Repetitive presynaptic activity was found not to be a necessary condition for eliciting long-lasting LTP (greater than 1 hr), as shown by experiments in which a single presynaptic impulse was paired with a brief heterosynaptic train. Factors increasing postsynaptic activity during the induction event, such as increased stimulus intensity, temporal pairing of two weak trains, or reduced postsynaptic inhibition, all reduced the relative amount of LTP decay. Moreover, partial pharmacological blockade of NMDA receptor channels increased the relative amount of decay. In conclusion, the amount of postsynaptic activity and associated NMDA receptor activation during the induction event appeared to be the main factor governing the early stability of LTP in the dentate gyrus.

Animals↗
PubMed1991

Synaptic potentiation in the hippocampal CA1 region induced by application of N-methyl-D-aspartate.

The effect of local pressure application of N-methyl-D-aspartate (NMDA) in the synaptic layer of CA1 pyramidal cells was investigated in the guinea pig hippocampal slice preparation using extracellular recording technique. Application of NMDA produced a transient depression and a subsequent 30-60 min potentiation of the field excitatory postsynaptic potential (EPSP) seen as an increase of the initial slope and amplitude of the EPSP. The increase in amplitude was consistently greater than that of the initial slope. Prior tetanization that caused saturation of long-term potentiation prevented the generation of an NMDA-induced potentiation of the initial slope for more than 1-2 h, but not the generation of an increase of the amplitude.

Animals↗
PubMed1991

Structural studies of the Vibrio cholerae O:3 O-antigen polysaccharide.

The structure of the Vibrio cholerae O:3 O-antigen polysaccharide has been investigated, mainly by n.m.r. spectroscopy, mass spectrometry, sugar and methylation analysis, and specific degradations, and is proposed to involve the following tetrasaccharide repeating-unit. [formula: see text]. In this structure, D-D-Hep is D-glycero-D-manno-heptose, Asc is 3,6-dideoxy-L-arabino-hexose (ascarylose), and Sug is 2,4-diamino-2,4,6-trideoxy-D-glucose (bacillosamine) in which N-2 is acetylated and N-4 is acylated with a 3,5-dihydroxyhexanoic acid. That the 2,4-diamino-2,4,6-trideoxy-D-glucose residue is linked through O-3 and not through one of the hydroxyl groups in the 3,5-dihydroxyhexanoyl group is indicated but not definitely proved. The configuration of the latter group has not been determined. The f.a.b.-mass spectrum of the methylated O-antigen indicates that the structure given above also represents the biological repeating-unit.

Carbohydrate Conformation↗
PubMed1991

Long-lasting potentiations evoked by a brief heterosynaptic tetanus in the guinea pig dentate gyrus in vitro.

The heterosynaptic effects induced by a brief afferent tetanization in the molecular layer of the dentate gyrus were investigated in the guinea pig hippocampal slice preparation using extracellular recording technique. At a brief interval (5 ms) between a single stimulation of the test afferents and the tetanus evoked in the conditioning afferents, a long-lasting (greater than 1 h) potentiation of the test field excitatory postsynaptic potential (EPSP) initial slope and amplitude was observed. This potentiation was occluded by prior homosynaptic tetanization of the test afferents, suggesting that it represents long-term potentiation (LTP). Thus, in the dentate gyrus, a single activation of a single test EPSP suffices to induce LTP when coinciding in time with a brief tetanus to other afferents. When not temporally paired with the test stimulation, i.e. at longer test-conditioning intervals (greater than 50 ms), the conditioning tetanus also elicited a long-lasting potentiation of the test field EPSP. This potentiation was, however, seen as a prolongation of the rising phase with no change in the field EPSP initial slope, and may represent a potentiation distinct from LTP.

Animals↗