Search PubMed⌕ Search

Biomedical subjects

B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 109 records · Page 6Linked to original sources
PubMed1991

Tumor cytokinetic effects of acute starvation versus polyamine depletion in tumor-bearing mice.

Previous investigations in our laboratory have demonstrated that both acute host starvation and polyamine depletion by means of the irreversible ODC-inhibitor (ODC = ornithine-decarboxylase) fluoro-methylornithine (DFMO) lead to pronounced growth retardation of rapidly proliferating tumors. The aim of this investigation was to elucidate how these different interventions affect cell kinetics and cell cycle phases in vivo. Adult nongrowing mice (C57Bl/J) bearing a poorly differentiated rapidly growing methylcholanthrene induced sarcoma were used. Combined measurements of bromodeoxyuridine incorporation into DNA and flow cytometric techniques were used. Starvation and DFMO treatment resulted in a prolonged cell cycle transit compared to freely fed animals. Tumor cells from DFMO-treated mice demonstrated an increased time for DNA synthesis and a relatively larger accumulation of cells in the G2M phase, whereas tumor cells from starved animals were accumulated in the G0G1 phase. The fractional cell loss of tumor cell during proliferation was calculated to be around 18% higher in DFMO-treated animals compared to starved and freely fed tumor-bearing mice. This study demonstrates that different mechanisms are involved in tumor growth suppression from substrate deficiency (starvation) and from inhibition of polyamine synthesis.

Animals↗
PubMed1991

Dysphagia, an unrecognized handicap.

The aim of this study was to examine whether esophageal dysphagia can be described as a handicap and to grade the severity of handicap as the discrepancy between the subject's own eating goals and his or her eating disability. The severity of the disability-goal-handicap (DGH) regarding dysphagia was expressed on a scale ranging from 0 to 48 points. Nineteen patients with dysphagia of differing causes were selected from a patient register at a laboratory for diagnostic procedures of the esophagus. The severity of handicap for the 19 patients was, on average, 33 points (range, 20-44). The DGH score correlated significantly with the patients' own evaluation of the severity of their dysphagia (p = 0.008). The DGH scores did not differ markedly based on patient's sex, age, or cause of dysphagia. Patients who were operated upon because of dysphagia had significantly more points on the DGH scale prior to operation than patients who were not (p = 0.001). Denial of dysphagia (N = 18), concealment of dysphagia (N = 18), and lack of confirmation by the patient's physician (N = 15) were common but did not influence the severity of handicap as assessed by the DGH scale. It was shown that dysphagia affects all aspects of life as expressed by reduction in self-esteem (N = 13), security (N = 16), work capacity (N = 8), exercise (N = 7), and leisure time (N = 6). Esophageal dysphagia may therefore be regarded as a handicap when assessed using the DGH code described in this study.

Adolescent↗
PubMed1991

Dysphagia and its consequences in the elderly.

This investigation was designed to study to what extent dysphagia in the elderly is accompanied by other chest symptoms and if it leads to a reduction in body weight and quality of life. To this end 796 persons, randomly taken from a population register, replied to a questionnaire concerning swallowing difficulties and other chest symptoms. Chest pain, heartburn, and regurgitation occurred significantly more frequently in subjects who admitted feelings of obstruction in the throat or chest during the ingestion of food (p less than 0.001) than in the rest, as did so-called heart problems (p less than 0.05). People with dysphagia had more often gained weight over the last 5 years than people without dysphagia (p less than 0.05). Psychosocial problems in those with dysphagia were given as anxiety at mealtimes and the wish to eat alone. Of those with dysphagia, 40% had consulted a physician, but despite this these patients had as many problems as those who had not seen a doctor. It is apparent that difficulty in swallowing in the elderly leads to physical and psychosocial problems that may reduce their quality of life.

Aged↗
PubMed1991

Evaluation of ornithine decarboxylase activity as a marker for tumor growth rate in malignant tumors.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of polyamines. Polyamines regulate DNA synthesis by a mechanism that is not fully understood. High levels of polyamines and ODC activity are associated with rapid cell growth, particularly in tumor tissues. The aim of this study was to determine whether ODC activity as a marker for rapid alterations in tumor growth could be used to investigate whether nutritional support in cancer patients stimulates tumor cell proliferation. Weight-losing head and neck cancer patients and tumor-bearing mice (MCG 101, C57/BL) were studied during different feeding regimens. The ODC activity in tumor tissue was investigated in relation to the following variables: (1) histopathologic differentiation; (2) DNA content; and (3) bromodeoxyuridine (BrdUrd) incorporation into DNA. After the animals were starved for 24 hours, a significant reduction of tumor growth was demonstrated in the experimental tumor along with a reduction of ODC activity, an accumulation of cells in the G0G1 phase, and a reduction of cells incorporating BrdUrd into DNA. Refeeding after 24 hours generated a response by all variables. Tumor biopsy specimens from patients with head and neck cancer malignancies demonstrated aneuploidy in the cells of 70% of the patients. High ODC activity in tumor tissue was demonstrated mainly among poorly differentiated tumors, and ODC activity was correlated with the compartment size of aneuploidic cells in the tumor. High ODC activity indicated a poor short-term survival (1 year). It was concluded that experimental tumor growth is highly dependent on host feeding. However, there was no evidence supporting the claim that nutritional support to cancer patients stimulates tumor cell proliferation. Determination of ODC activity may be used to monitor rapid changes in DNA synthesis and may have prognostic significance for survival.

Aged↗
PubMed1991

Proliferative pattern of head and neck cancer.

Tumor growth is primarily dependent on the fraction size of growing cells, their growth and proliferative rate, and the fractional cell death. In the present study, we focused specifically on the proliferative characteristics of squamous cell carcinomas of the head and neck region by using monoclonal antibodies and immunohistochemical methods. We studied two normally occurring antigens representative of cell proliferation: (1) ribonucleotide reductase, which is an independent cytoplasmatic enzyme and is intimately integrated in DNA synthesis, and (2) Ki-67, which is a nuclear antigen being expressed only in replicative cells. We also used intravenously injected bromodeoxyuridine (BRDU) for specific detection of tumor cells in the S phase of the cell cycle. In addition, in vivo injections of BRDU were also given to tumor-bearing mice to illustrate tumor cell kinetics by means of flow cytometry. The main observation was morphologic heterogeneity, with a high frequency of proliferative cell clusters in the cancer specimens interspersed among quiescent cells, which was demonstrated by the three monoclonal antibodies independent of each other. The experimental studies clearly visualized the transfer of BRDU throughout the tumor cell cycle. We conclude that immunohistochemical analysis provides valuable qualitative information on the proliferative pattern of tumor growth and, together with dynamic flow cytometry, may improve the clinical basis for individualized management of the cancer patient.

Animals↗
PubMed1991

The intrauterine contraceptive device, "Multiload Cu 250": a regulatory problem.

Reports to the control agencies in Sweden and Australia of fractures of the intrauterine contraceptive device. Multiload Cu 250, led to a review of the safety of this device in these countries. The review revealed that fractures of the device had occurred in 15 other countries but in these countries only 5% of reports had been directed to the relevant national control authorities. The remainder either had been reported to the sponsor or had appeared in the published literature. An additional problem identified was one of thread rupture with the resultant difficulty in removal and the need for surgical intervention. It is apparent that the sponsor of the device was aware of the problems for some time since it made several significant changes to the device marketed in Sweden. These changes were made in 1983, without informing the Swedish agency and without its approval. These were 1622 Multiload Cu 250 devices returned to the Swedish agency for examination from 1988 to 1989. An analysis of 1516 of them found that the overall incidence of device fracture was 1:405 and of broken threads, 1:8. However, evidence suggests that the modifications conducted in 1983 and 1984 resulted in a device with very much less chance of fracture and/or ruptured threads on removal. Stress testing of 106 used devices suggested that the risk of fracture may increase with the length of time left in utero. Regulatory action in both Sweden and Australia involved changes in the information provided to physicians and patients. In Sweden, the additional step of withdrawing all earlier devices suspected of being associated with fracture and/or ruptured threads was taken.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia↗
PubMed1991

Plasma exudation as a first line respiratory mucosal defence.

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Absorption↗
PubMed1991

Toluene diisocyanate produces an increase in airway tone that outlasts the inflammatory exudation phase.

Toluene diisocyanate (TDI) is a causative agent in occupational asthma. Through an oral catheter TDI, 0.03 microliters, dissolved in 0.02 ml olive oil, was superfused on the tracheobronchial mucosa of anaesthetized guinea-pigs. TDI induced plasma exudation into both airway tissue and lumen (peak effect: 5 hr; duration approximately 17 hr). Light microscopy examinations demonstrated that the epithelium was not disrupted by this process (and that microvessels are abundant just beneath the epithelium). At days 6 and 21 after exposure to TDI PAS-positive cells were increased, but no other histological alterations were found. Also, the occurrence of peptide-containing nerve fibres was not altered by TDI. After TDI-exposure the airway smooth muscle tone was elevated as examined in vitro at base-line and at concentration-response to carbachol. The largest increases in tone were recorded 21 days after exposure to TDI. The abnormally large tone was not associated with an increased thickness of the smooth muscle layer nor was it associated with reduced effects of either beta 2-agonist (terbutaline) or xanthine- (theophylline) relaxants. It is concluded that TDI-induced plasma exudation into guinea-pig airways occurs for 17 hr without disrupting the epithelial lining and without causing major changes in the airway peptidergic innervation. Both the airway tone, and the number of mucous cells, are increased for at least 3 weeks after exposure to TDI.

Airway Resistance↗
PubMed1991

Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents.

"Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three antimuscarinic drugs were also examined to determine whether antagonism of mediators other than muscarinic agonists might contribute to bronchodilatation by these antimuscarinic drugs. Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M), theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after indomethacin treatment. They did not, however, alter the carbachol concentration-response curve significantly. In addition, neither theophylline (2.2 x 10(-4) M) nor terbutaline (1.1 x 10(-7) M) altered histamine induced contraction. Atropine sulphate, glycopyrrolate, and ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by allergen and nine other non-muscarinic mediators. It is suggested that bronchodilatation by antimuscarinic drugs in vivo is due to inhibition of acetylcholine induced bronchoconstriction alone and that beta 2 agonists and xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in asthma seen with beta 2 agonists and xanthines.

Animals↗
PubMed1991

SPAM-8, a mouse-human heteromyeloma fusion partner in the production of human monoclonal antibodies. Establishment of a human monoclonal antibody against cytomegalovirus.

A heteromyeloma (mouse x human) cell line (SPAM-8) was produced by fusing mouse myeloma cells (SP2/0) with human peripheral blood lymphocytes. The cells were sensitive to aminopterin and resistant to ouabain. The cells showed a doubling time of about 19 hours and a cloning efficiency of 0.8 cells/well (to obtain growth in 50% of wells seeded) using mouse thymocytes as feeder cells. The number of chromosomes was about 86 and 1% of the total DNA was of human origin. Fusion of SPAM-8 cells with lymphocytes prepared from human spleens resulted in approximately one hybridoma per 10(5) seeded lymphocytes. A trioma (human x [mouse x human]) cell line was established by fusing cells of an Epstein-Barr virus-transformed B cell line with SPAM-8 cells. The trioma cells produced antibodies (IgG1, K) against cytomegalovirus, in a concentration of 7 micrograms/ml in spent medium, over a period of six months of continuous culture. The results obtained indicate that the heteromyeloma SPAM-8 may be used as a fusion partner in the production of human monoclonal antibodies.

Animals↗
PubMed1990

The early decay of long-term potentiation in the hippocampal CA1 region in vitro is reduced by activators of protein kinase C.

The effect of the exogenous protein kinase C (PKC) activator phorbol-12,13-diacetate (PDAc) on the early (0-10 min) time course of long-term potentiation (LTP) has been studied in the CA1 region of the guinea pig hippocampal slice. As shown previously, following a brief tetanus LTP develops almost linearly towards a peak value within 20-25 s, and decays thereafter rapidly to about a third of the peak value within 10 min after tetanization before a more stable level is reached. In the presence of 1.0 microM PDAc the growth phase of LTP is prolonged to 40-50 s, and the subsequent early decay is reduced. This reduction of the early decay resembles that previously found when increasing the number of afferent impulses of the LTP-generating tetanus. Examination of the early time course in solutions with different calcium-magnesium concentration ratios suggests that the observed effect of PDAc is not directly mediated via a change in presynaptic release probability, another effect observed after phorbol ester application. The results show that PKC activity is involved in the early stage of LTP development and support the idea that the early phase of LTP represents the same modification process as that underlying the more sustained phase of LTP.

Animals↗
PubMed1990

Determination of tauromustine and its demethylated metabolites in plasma and urine.

A sensitive, selective and precise high-performance liquid chromatographic method for simultaneous determination of tauromustine and its demethylated metabolites in plasma and urine has been developed. It is based on solid-phase extraction on C18 sorbent and separation on a semipolar column. The analytical procedure is described in detail. The method has been validated with respect to linearity, recovery, selectivity, precision and detection limit. The stability of the determined substances in various media has also been studied.

Antineoplastic Agents↗
PubMed1990

Changes in field excitatory postsynaptic potential shape induced by tetanization in the CA1 region of the guinea-pig hippocampal slice.

The present paper contains a description of a prolonged potentiation of the field excitatory postsynaptic potential in the CA1 region of the hippocampal slice preparation following afferent tetanization. In contrast to long-term potentiation, this novel potentiation is not specific to the activated synapses, and manifests itself as a change in the shape of the field excitatory postsynaptic potential with a prolongation of the rising phase and an increased peak amplitude. The potentiation is fully developed within minutes after tetanization and shows no decrement for at least an hour. Although it can appear together with long-term potentiation following tetanization at moderate strength (single volley excitatory postsynaptic potential below threshold for spike initiation), it is more readily seen following tetanization at higher strengths. The N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate prevents the induction but not the maintenance of the shape modification. The potentiation is observed in the presence of the GABAA antagonist picrotoxin (100 microM) and is thus not secondary to changes in postsynaptic inhibition. 4-Aminopyridine (50-100 microM) produced changes in the field excitatory postsynaptic potential resembling the shape modification produced by afferent tetanization, suggesting that the potentiation may be due to a blockade of potassium channels, pre- or postsynaptically located. The potentiation is also found to be associated with an increase in the population spike for a given initial slope of the field excitatory postsynaptic potential, and may thus contribute to the excitatory postsynaptic potential-spike potentiation that can be observed following afferent tetanization.

2-Amino-5-phosphonovalerate↗
PubMed1990

Long-term potentiation in the hippocampal CA1 region: its induction and early temporal development.

Long-term potentiation (LTP) is a process that due to its prolonged time course and associative nature of induction is believed to be involved in learning and memory in the mammalian brain. In this chapter the experimental evidence for the view that LTP is initiated by an influx of calcium ions through synaptically controlled N-methyl-D-aspartate (NMDA) receptor channels is discussed. It will also be described how LTP develops following its induction. It will be shown that there is a considerable delay, about 2-3 s, between a tetanus and the initiation of LTP, and that additional 20-30 s are needed for the potentiation to reach peak levels. The potentiation subsequently decays to a degree which depends primarily on tetanus length. It will be argued that this early phase of tetanus-induced LTP is of the same nature as that present a few hours later.

Action Potentials↗
PubMed1990

Amperozide--a new putatively antipsychotic drug with a limbic mode of action on dopamine mediated behaviour.

Amperozide, a new putatively antipsychotic drug, was found to exert a functional selectivity for the limbic system of the brain. Thus, amperozide was as active as both classical and atypical neuroleptics on hypermotility induced by a low dose of amphetamine. On the other hand, amperozide did not produce catalepsy, nor did it reverse amphetamine-induced stereotypies. Moreover, amperozide inhibited exploratory behaviour in mice. The present results indicate an antipsychotic effect of amperozide, with a minimal risk for EPS when used in the clinic.

Animals↗
PubMed1990

Amperozide and conditioned behaviour in rats: potentiation by classical neuroleptics and alpha-methylparatyrosine.

Amperozide, a new putatively antipsychotic compound, has been evaluated for its effect on conditioned avoidance response and food-reinforced lever-pressing. Given alone, amperozide was almost equipotent to clozapine, but less potent than haloperidol in both test models. It was found that there was a statistically significant synergism, in these two models, between amperozide and classical neuroleptics. Since amperozide is inactive in behavioural tests reflecting striatal dopaminergic mechanisms, the synergistic effect could be of great therapeutic value in the treatment of psychotic disorders.

Animals↗
PubMed1990

Amperozide and emotional behaviour.

The new putatively antipsychotic drug amperozide is characterized pharmacologically by a specific limbic mode of action. Thus amperozide is a potent antagonist of muricidal behaviour (ED50 = 0.16 mg/kg) as well as aggression between isolated male mice. Although amperozide displays anxiolytic properties in Vogel's conflict test as well as an antidepressive effect in the despair test, the drug does not interfere with motor coordination or cause sedation (ED50 greater than 50 mg/kg). These results could make amperozide very interesting as an antipsychotic drug in the clinic, with effect on both positive and negative symptoms.

5-Hydroxytryptophan↗