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B Gustafsson

Publications and source records attributed to B Gustafsson.

At least 55 records · Page 3Linked to original sources

Short-term facilitation evoked during brief afferent tetani is not altered by long-term potentiation in the guinea-pig hippocampal CA1 region.

1. The aim was to examine whether long-term potentiation (LTP) had effects on short-term synaptic plasticity outside those predicted from its effect on single volley-induced responses. Field recordings from the CA1 region of guinea-pig hippocampal slices were used, and short- term plasticity was evoked by five-impulse trains of 20 and 50 Hz. 2. The five-impulse trains were evoked in the presence of D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 20-50 microM), picrotoxin (100 microM), and 2-OH-saclofen (200 microM), and care was taken to avoid initiation of postsynaptic spike activation. Field responses were thus considered to reflect non-NMDA receptor-mediated activity only, and demonstrated a net facilitation during the trains. 3. The facilitation was found, on average, to be unaffected by LTP, evoked by strong afferent tetanization. This was true also when release probability had been altered either by the adenosine agonist N-cyclohexyladenosine (CHA; 100 nM) or the antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 200 nM). When examined for individual experiments, cases with increases, or decreases, of facilitation following LTP were observed. These deviations showed no relation to initial release probability or to LTP magnitude, and they were also observed in control inputs not subjected to LTP. 4. Impairment of non-NMDA receptor desensitization by cyclothiazide (30 microM) increased facilitation observed during a 50 Hz, but not a 20 Hz, train. LTP had no effect on facilitation, in the presence of this drug, either during 20 or 50 Hz trains. 5. The results suggest that the effect of LTP in the hippocampal CA1 region on non-NMDA receptor-mediated synaptic responses to a brief afferent tetanus does not differ from that on a low-frequency, single volley-induced response. They do not support the notion that LTP is based on changes in release probability of previously active synapses. If LTP is based on recruitment of previously, pre- or postsynaptically, silent synapses, these synapses must have, on average, release characteristics similar to the previously active ones.

2-Amino-5-phosphonovalerate↗

Distinct expressions for synaptic potentiation induced by calcium through voltage-gated calcium and N-methyl-D-aspartate receptor channels in the hippocampal CA1 region.

Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-D-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-D-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed. Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.

Animals↗

Allergen challenge-induced extravasation of plasma in mouse airways.

BACKGROUND: Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. OBJECTIVE: This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. METHODS: Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. RESULTS: Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. CONCLUSION: The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

Aerosols↗

A modified fast micro method in agarose for isotype, allotype, light chain and idiotype-specific analysis of antibody clonotypes to bacterial virulence antigens.

A modified fast micro method for spectrotypic/clonotypic analysis of human IgG1-4 antibodies against bacterial virulence antigens of polysaccharide or protein nature is described. Serum samples of as small volumes as 0.5 microliter were isoelectrically focused in micro agarose gels made in plexiglass matrices and blotted using immunoaffinity-mediated capillary blotting onto nitrocellulose membranes previously coated with antigen. The bands of the antigen-specific antibodies were identified with respect to isotypes, light chain types, allotypes or idiotypes by incubating the nitrocellulose membranes with mouse monoclonal anti-human IgG subclass antisera and then with alkaline phosphatase-conjugated rabbit anti-mouse immunoglobulins. The method was applied for characterization of human monoclonals against tetanus toxoid (TT) and for the analysis of variable patterns of clonotypes in IgG subclass-deficient patients. The usefulness of the technique was also demonstrated by comparing the variable specificity and reactivity of different commercial monoclonals against human IgG subclasses. This method is fast, specific, sensitive, uses little material, is simple and reproducible.

Animals↗

Effect of IFN-alpha on tumor-infiltrating mononuclear cells and regressive changes in metastatic malignant melanoma.

Interferon-alpha (INF-alpha) has a documented activity against metastatic melanoma. To what extent an antiproliferative effect or tumor cell modulation or immunomodulation contributes to this antitumor effect is still uncertain. The role of immune mechanisms in the control of malignant melanoma is suggested by several studies. Therefore, this investigation used monoclonal antibodies, anti-CD4, anti-CD8, and anti-CD11c, to study the occurrence and distribution of tumor-infiltrating mononuclear cells in 10 untreated and 26 IFN-alpha-treated patients with regional metastatic malignant melanoma. IFN-alpha was given for 1-3 weeks before resection of the metastases. The infiltration of mononuclear cells in the stroma and close to tumor cells was studied. The duration of IFN-alpha treatment was found to be of importance for the immunomodulatory effect. In patients treated for < or = 1 week, tumor-infiltrating mononuclear cells were still mainly localized in the stroma, similar to the situation in untreated patients. The differences in CD4+ cells close to the tumor cells, comparing untreated patients and patients with various durations of IFN-alpha treatment, were highly significant (p = 0.009). Thus, IFN-alpha treatment resulted in recruitment of CD4+ cells close to the tumor cells. IFN-alpha had only a weak effect on the recruitment of CD8+ and CD11c+ mononuclear cells close to the tumor cells. Regressive changes in metastases were also analyzed and correlated to duration of treatment. Some of the criteria used for histopathologic regression in primary melanoma (distorted histologic architecture, low tumor cell density, and fibrosis) were applied to analyze the effect of IFN-alpha in metastatic melanoma. The tumor cell density was found to be significantly reduced in metastases with marked tumor regression compared with metastases with no, or only minor, regressive changes (p < 0.005). A chi-square analysis for trend, comparing untreated patients and patients with various durations of IFN-alpha treatment, showed that regressive changes of the tumor increased significantly during IFN-alpha treatment (p = 0.02).

Adult↗

NMDA receptor dependence of the input specific NMDA receptor-independent LTP in the hippocampal CA1 region.

An important characteristic of long-term potentiation (LTP) in the hippocampal CA1 region is that it is specific for those synapses which are active during the induction event. This input specificity is commonly attributed to the location and properties of the N-methyl-D-aspartate (NMDA) receptor channel. Experiments using strong high-frequency orthodromic activation have suggested that input-specific LTP can occur also in the absence of NMDA receptor activation. The present experiments have re-examined this question. They were performed in the CA1 region of hippocampal slices, and the synaptic strength was evaluated from the initial slope of the dendritically recorded field potential. In agreement with previous reports, 0.5 s, 200 Hz, orthodromic trains were found to lead to a substantial input-specific LTP (averaging 62%) in the presence of the competitive NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) (20 microM). Under conditions of higher NMDA receptor blockade considerably less LTP was evoked. In 50 microM D-AP5 and 20 microM chloro-kynurenate LTP averaged 13.4%, and after addition of 20 microM (+)-dizicilpine maleate (MK-801) LTP averaged 5.9%. On the other hand, in 20 microM D-AP5 and 20 microM of the calcium channel antagonist nifedipine LTP averaged 49.9%. The present results suggest that NMDA receptor activity remaining in high concentrations of AP5 is sufficient to underly LTP induction under strong induction conditions.

2-Amino-5-phosphonovalerate↗

Long-term potentiation induced by single volley activation: a mechanism for bicuculline-induced enhancement of synaptic field potentials in the CA1 hippocampal region.

Long-term potentiation in the CA1 region is often evaluated as the change in the initial slope of the field response following a single test stimulus. This change is thought to represent an alteration of excitatory transmission only. However, it has recently been reported that this initial part of the field response is also controlled by a picrotoxin-resistant GABA(A)ergic response since bicuculline (100 microM), in the presence of picrotoxin, could lead to a substantial increase in the field response initial slope. A disinhibition may then be an important factor underlying expression of what is believed to be long-term potentiation of excitatory synaptic transmission. Alternatively, the bicuculline-induced field response enhancement could be due to an induction of long-term potentiation favoured by the low magnesium (1.25 mM) and high calcium (4 mM) concentrations used in these experiments. Results presented here show that neither picrotoxin (100 microM), nor bicuculline (100 microM), produce any significant change in field response initial slope, when examined using 4 mM magnesium and calcium in the perfusion fluid. In experiments using lower magnesium (1-1.5 mM), the same result was observed in most cases. In some cases, the field response following single test stimuli became temporally paired with spontaneous bursts of spike activity, and its initial slope became considerably enhanced (100%). Similar results could be provoked by a temporary increase in stimulus strength sufficient to evoke spike activity. This potentiation occluded a subsequent long-term potentiation induced by afferent tetanization, and it was not observed when a N-methyl-D-aspartate receptor antagonist was present in the perfusion solution. The present results suggest that the bicuculline-induced enhancement of the field response initial slope represents an induction of long-term potentiation rather than being a direct consequence of pharmacological blockade of a GABA(A)ergic process.

2-Amino-5-phosphonovalerate↗

Effect of interferon-alpha on the expression of tumour necrosis factor-alpha by metastatic malignant melanoma in vivo.

To our knowledge modulation of the expression of tumour necrosis factor-alpha (TNF-alpha) in malignant melanoma metastases in vivo has not been reported. The expression of TNF-alpha by malignant melanoma cells was studied immunohistochemically using an anti-TNF-alpha antibody. The specificity of the staining reaction was demonstrated by absorption of the TNF-alpha antibody with human recombinant TNF-alpha, which inhibited the staining reaction. The TNF-alpha expression was also verified by in situ hybridization for mRNA. Metastases from 37 patients were studied, 21 of whom were treated with IFN-alpha. All 16 metastases from untreated patients were positive for TNF-alpha. Based on the average staining intensity of the melanoma cells for TNF-alpha, the metastases were classified into two groups. The expression of TNF-alpha varied considerably between metastases from different patients and also within the same metastasis. Melanoma cells in areas with low cellularity and large numbers of infiltrating inflammatory cells were generally weakly stained. This is in good agreement with a low staining score for TNF-alpha in metastases showing marked histopathological regression. Seven out of 13 patients with a low staining score for TNF-alpha showed a marked regression of their tumours. In contrast one out of five patients with a high staining score for TNF-alpha showed a marked tumour regression, suggesting that tumour cells sensitive to immune-mediated regression express less TNF-alpha. Interferon-alpha (IFN-alpha) appears to modulate the expression of TNF-alpha. Significantly more patients treated with IFN-alpha had metastases with a low TNF-alpha staining score compared with untreated patients. Thus, seven out of 21 patients treated with IFN-alpha showed a high expression of TNF-alpha in contrast to 13 out of 16 in the untreated group (P = 0.01).

Adult↗

IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat.

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.

Animals↗

Detection of the response regulator AgrA in the cytosolic fraction of Staphylococcus aureus by monoclonal antibodies.

The expression of many virulence genes in Staphylococcus aureus is controlled by a regulatory RNA molecule, RNAIII, which is encoded by the agr locus. Transcription RNAIII requires the activity of the agrA, B, C and D genes, which code for components of a quorum sensing signal transduction system. In this report we describe the overexpression and purification of the response regulator, AgrA. Monoclonal antibodies were produced and used to detect AgrA in the cytosolic fraction of S. aureus cells. Purified AgrA did not bind to the RNAIII promoter region in a DNA mobility shift experiment. This confirms previous results obtained with protein extracts from agr+ and agr- cells.

Amino Acid Sequence↗

Long-term potentiation and paired-pulse facilitation in the hippocampal CA1 region.

We have investigated the interaction between long-term potentiation (LTP) and paired-pulse facilitation (PPF) in the hippocampal CA1 region under different conditions of initial PPF. PPF is a short lasting presynaptic alteration in synaptic efficacy, determined by the presynaptic release probability, where a high and low PPF indicate a low and high release probability, respectively. LTP was associated with no, or only little, change in PPF, independent of the initial value of PPF and of the time of measurement within the first hour of LTP. These results support the notion that the expression mechanism of LTP is not regulated by the initial release probability and that LTP is due to a single expression mechanism within its first hour.

Animals↗

Ionotropic glutamate receptors. Their possible role in the expression of hippocampal synaptic plasticity.

In the brain, most fast excitatory synaptic transmission is mediated through L-glutamate acting on postsynaptic ionotropic glutamate receptors. These receptors are of two kinds--the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (non-NMDA) and the N-methyl-D-aspartate (NMDA) receptors, which are thought to be colocalized onto the same postsynaptic elements. This excitatory transmission can be modulated both upward and downward, long-term potentiation (LTP) and long-term depression (LTD), respectively. Whether the expression of LTP/LTD is pre-or postsynaptically located (or both) remains an enigma. This article will focus on what postsynaptic modifications of the ionotropic glutamate receptors may possibly underly long-term potentiation/depression. It will discuss the character of LTP/ LTD with respect to the temporal characteristics and to the type of changes that appears in the non-NMDA and NMDA receptor-mediated synaptic currents, and what constraints these findings put on the possible expression mechanism(s) for LTP/LTD. It will be submitted that if a modification of the glutamate receptors does underly LTP/LTD, an increase/ decrease in the number of functional receptors is the most plausible alternative. This change in receptor number will have to include a coordinated change of both the non-NMDA and the NMDA receptors.

Animals↗

Correlations of Ki-67 and PCNA to DNA ploidy, S-phase fraction and survival in uveal melanoma.

In 79 patients with uveal melanoma, the tumours were investigated by DNA flow cytometry and immunohistochemical staining of PCNA and Ki-67. S-phase as a continuous variable was significantly correlated with Ki-67 (P = 0.033), but not with PCNA. DNA ploidy was not correlated with either of the two antigens. Ki-67 was significantly correlated with histopathological type (P < 0.001) and tumour size (P < 0.001). Large tumours and epithelioid cell type were associated with a high frequency of Ki-67 positive cells. A high level of Ki-67 positivity (> or = 6.5%) was also associated with a shorter survival (P = 0.0037), and when adjusted for DNA ploidy, histopathological type and tumour size, Ki-67 in the multivariate analysis remained an important prognostic factor (P = 0.017).

Antigens, Neoplasm↗

Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment.

Interferon alpha (IFN-alpha) has a documented activity against malignant melanoma with a response rate of only approximately 20%. It would therefore be of considerable importance if patients likely to respond could be identified. The degree of mononuclear cell infiltration in primary tumours has been reported to correlate with a favourable prognosis. This investigation used monoclonal antibodies, anti-CD4, -CD8 and -CD11c, to identify subsets of tumour-infiltrating mononuclear cells in fine needle aspirates to study whether the presence of such cells correlates with the therapeutic effect of IFN-alpha. Twenty-one patients with systemic and 20 with regional metastatic malignant melanoma were studied before initiation of IFN-alpha treatment. A statistically significant correlation (P < 0.001) was found between the occurrence of CD4+ lymphocytes in fine needle aspirates and the therapeutic benefit of IFN-alpha in patients with systemic disease. Ten out of 11 with moderate to high numbers of infiltrating CD4+ lymphocytes achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, nine out of ten had progressive disease. Similar results were found in patients with regional disease.

Adult↗

Localization of IL-1, IL-2, IL-4, IL-8 and TNF in superficial bladder tumors treated with intravesical bacillus Calmette-Guerin.

PURPOSE: Cytokines have been detected in the urine during the first hours after intravesical Bacillus Calmette Guerin (BCG) treatment against superficial bladder cancer. To investigate the long-lasting mucosal inflammatory response, we analyzed intracellular cytokines by immunohistochemistry in biopsies taken 2 weeks after BCG treatment. MATERIALS AND METHODS: Tumor biopsies were obtained from 8 patients with noninvasive, papillary transitional cell carcinoma (TCC), and intracellular cytokines were visualized by immunohistochemistry using cytokine-specific monoclonal antibodies. RESULTS: Interleukin (IL)-1 beta+ or tumor necrosis factor (TNF)-alpha+ cells were abundant in tumor and stroma. Interleukin-1 alpha, IL-2, IL-4, IL-8 and TNF-beta were variably expressed, while IL-10+ and interferon (IFN)-gamma+ cells were not detected. Among the few patients studied (5 responders and 3 nonresponders to BCG treatment) no single cytokine or cytokine profile was associated with clinical response to BCG therapy. CONCLUSION: We conclude that the in situ cytokine response after BCG treatment is highly complex, since cytokine profiles differed among the 8 patients investigated and between tumor and surrounding tumor-free mucosa. Further studies, investigating larger numbers of patients, is required to clarify whether cytokine profiles correlate with the clinical response to BCG.

Administration, Intravesical↗

Milking is a high-risk job for young females.

The prevalence of and the impact of selected factors on self-reported musculoskeletal complaints in Swedish female milkers with special reference to symptoms in the upper extremities were investigated using data from mail-in surveys. An agricultural study group was formed of three subgroups: 161 active milkers, 108 non-milkers and 62 ex-milkers, women who had been milkers earlier but were no longer doing that kind of work. In the course of the analysis these subgroups were compared with each other and also, separately or in combinations, with a non-agricultural population consisting of 166 nursing assistants. Problems in the upper extremities were significantly more common in the agricultural group than in the non-agricultural group. Milkers ran a higher risk of developing symptoms in the wrists and hands than non-milking women. Symptoms such as numbness, coldness in the wrists and white fingers were more common in all agricultural subgroups than in the non-agricultural group. Numbness and white fingers were related to vibration exposure in the ex-milker and the non-milker groups but not in the milker group. Psychosocial factors such as occupational well-being were not related to the occurrence of symptoms. Milking in a modernized barn gave fewer problems in elbows than milking in a traditional barn. Milkers who had received ergonomic instruction on how to work in order to reduce muscle stress had fewer problems in the elbow region than those who had received no such information.

Adult↗

Assessing poverty: some reflections on the literature.

"This paper examines the quantitative poverty measurement literature. After describing the literature a number of issues in poverty research are discussed. It can be concluded that the framework for poverty assessments is not always fixed. Much has been written about the poverty line but the issue of updating it seems to have attracted less attention than deserved. Substantial advancements in poverty research have been gained by fuller reports on the extent of poverty through the use of poverty indices and because of increased availability of panel data."

Economics↗