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Biomedical subjects

J Andersson

Publications and source records attributed to J Andersson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Relatively high risk of treatment failure after prostatectomy: tumour grade, histopathological stage and the preoperative serum PSA level are key prognosticators.

OBJECTIVE: Prostate cancer is the most common malignancy among males in Sweden. Any reduction in morbidity and mortality would require early detection of cases in which curative treatment is achievable. MATERIAL AND METHODS: From 1994 through 1998. 105 patients with clinically localized T1-T2 tumours were subjected to radical prostatectomy at our department. Three patients were lost to follow-up. We obtained clinical information from the patients' medical records and used pathologist reports to characterize the tumours with respect to grade and histopathological stage. We used serum PSA levels as a surrogate end-point, with a level equal to or above 0.6 ng/ml designated as treatment failure. Outcome was examined with respect to tumour grade, histopathological stage and preoperative PSA level. RESULTS: Altogether, 29% of the patients showed PSA failure during follow-up which varied between 2 and 6 years. No mortality due to prostate cancer was recorded during this time period. We found that tumour grade, histopathological staging and as well as the preoperative PSA level correlated with treatment failure (p<0.01). About 80% of the patients with a preoperative PSA <10 ng/ml showed no signs of treatment failure. The corresponding figure for those with PSA above 10 ng/ ml was 55%. The outcome for patients with a PSA between 10-20 did not seem to be better than that for patients with a preoperative PSA >20 ng/ml. CONCLUSION: Our study indicates, that the risk of treatment failure depends strongly on the grade of the tumour and increases when preoperative PSA value is greater than l0 ng/ml.

Follow-Up Studies↗
PubMed2001

Antisense inhibition of the photosynthetic antenna proteins CP29 and CP26: implications for the mechanism of protective energy dissipation.

The specific roles of the chlorophyll a/b binding proteins CP29 and CP26 in light harvesting and energy dissipation within the photosynthetic apparatus have been investigated. Arabidopsis was transformed with antisense constructs against the genes encoding the CP29 or CP26 apoprotein, which gave rise to several transgenic lines with remarkably low amounts of the antisense target proteins. The decrease in the level of CP24 protein in the CP29 antisense lines indicates a physical interaction between these complexes. Analysis of chlorophyll fluorescence showed that removal of the proteins affected photosystem II function, probably as a result of changes in the organization of the light-harvesting antenna. However, whole plant measurements showed that overall photosynthetic rates were similar to those in the wild type. Both antisense lines were capable of the qE type of nonphotochemical fluorescence quenching, although there were minor changes in the capacity for quenching and in its induction kinetics. High-light-induced violaxanthin deepoxidation to zeaxanthin was not affected, although the pool size of these pigments was decreased slightly. We conclude that CP29 and CP26 are unlikely to be sites for nonphotochemical quenching.

Amino Acid Sequence↗
PubMed2001

Net effect of memory collaboration: how is collaboration affected by factors such as friendship, gender and age?

The purpose of the study was to investigate explicit spatial and verbal collaborative memory performance. Factors such as friendship, age and gender were chosen for ecological and theoretical reasons. In Experiment 1 friendship and age were studied. The task was to retrieve the location of 25 pictures, which were presented in a 5 x 5-matrix grid. All participants retrieved once individually and once dyadically. Dyads were compared to the predicted base line, i.e., the pooled score from two participants working on their own (the same participants as in the dyad). Based on cognitive development aspects and collaboration data, it was predicted that the young collaborating dyads would not be able to reduce the net negative effects of collaboration to the same extent as older dyads. The findings revealed that, (1) dyadic collaboration affected spatial memory performance negatively, i.e., net negative effects of collaboration; (2) older (15-years-old), as opposed to young (7-years-old) dyads, reduced the net negative effects of collaboration and; (3) friend dyads, regardless of age, were able to reduce the net negative effect. In experiment 2, gender differences were studied in two explicit memory tasks. The purpose was to investigate if earlier findings of collaboration can be generalised to another ecological aspect of group composition, i.e., gender. Gender differences were studied at individual and group level. The results suggest that gender related memory differences exist on an individual and dyadic level in terms of absolute scores. Women remember explicit memory tasks to a greater degree than men. No main effect was found for gender in collaboration, i.e., both genders suffered compared to predicted potential.

Adolescent↗
PubMed2001

Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy.

Production of the C-X-C chemokines interleukin-8 (IL-8) and growth-regulated oncogene alpha (GRO-alpha) in macrophages is stimulated by exposure to human immunodeficiency virus type 1 (HIV-1). We have demonstrated previously that GRO-alpha then stimulates HIV-1 replication in both T lymphocytes and macrophages. Here we demonstrate that IL-8 also stimulates HIV-1 replication in macrophages and T lymphocytes. We further show that increased levels of IL-8 are present in the lymphoid tissue of patients with AIDS. In addition, we demonstrate that compounds which inhibit the actions of IL-8 and GRO-alpha via their receptors, CXCR1 and CXCR2, also inhibit HIV-1 replication in both T lymphocytes and macrophages, indicating potential therapeutic uses for these compounds in HIV-1 infection and AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Middle cerebral artery occlusion and reperfusion in primates monitored by microdialysis and sequential positron emission tomography.

BACKGROUND AND PURPOSE: In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen [CMRO(2)] to approximately 60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO(2) above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. METHODS: Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO(2) was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). RESULTS: The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. CONCLUSIONS: This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.

Animals↗
PubMed2001

Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women.

The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRbeta-dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater in placentae from HIV-1-infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.

Adult↗
PubMed2000

Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens.

In this study we compared the ability of different immunoglobulin (Ig) preparations containing IgG, IgM, and/or IgA to neutralize the activity of streptococcal pyrogenic exotoxin A (SpeA) or culture supernatant from a clinical group A streptococcal isolate. All Ig preparations markedly inhibited the mitogenic and cytokine-inducing activity of SpeA and culture supernatant at concentrations of 0.05-0.5 mg/mL, and at 0.5 mg/mL, most caused 95-100% inhibition of both stimuli. A significantly higher (P< or =.05) inhibition of SpeA was achieved by Pentaglobin (IgG, IgM, and IgA) and IgAbulin (IgA and IgG), as compared with pure IgG preparations. IgM- and IgA-enriched preparations had significantly higher inhibitory activity against SpeA than against culture supernatant, whereas the reverse was true for the IgG preparations (P< or =.05). The data show that IgM and IgA are potent inhibitors of specific streptococcal superantigens. These findings may have implications for the optimization of immunotherapy in invasive streptococcal infections.

Culture Media, Conditioned↗
PubMed2000

Human immunodeficiency virus type 1 infection is associated with significant mucosal inflammation characterized by increased expression of CCR5, CXCR4, and beta-chemokines.

Mucosal inflammation is characterized by increased expression of proinflammatory cytokines and chemoattractant chemokines, resulting in infiltration of immunocompetent cells. This study compared the degree of mucosal inflammation in human immunodeficiency virus type 1 (HIV-1)-infected gut mucosa with that in tissue samples from subjects with inflammatory bowel disease (IBD) and from healthy seronegative control subjects. Gut mucosal biopsy specimens were immunohistochemically stained and were evaluated by in situ imaging. There was significantly increased expression of HIV-1 coreceptors CCR5 and CXCR4, beta-chemokine RANTES, and macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, as well as increased numbers of T cells in lamina propria of HIV-1-infected patients. The results were similar in patients with IBD and in HIV-1-infected patients, suggesting increased inflammation in the colon of HIV-1-infected patients. To further investigate the effect of inflammation in HIV-1-infected lamina propria, treatments that reduce immune activation in lamina propria must be evaluated.

Biopsy↗
PubMed2000

Normalization of immune activation in lymphoid tissue following highly active antiretroviral therapy.

Although significant progress has been made in understanding immune reconstitution in peripheral blood following highly active antiretroviral therapy (HAART), less is known about immune changes in lymphoid tissue. Here, the expression of cytokine proteins (interferon gamma [IFN-gamma], interleukin [IL]-2, IL-4, IL-10, IL-1alpha, and IL-1beta) and surface antigens (CD4, CD8, CD1a, CD68) as well as cellular proviral HIV-1 DNA were determined in sequential tonsil biopsies before and at 4, 12, and 48 to 56 weeks posttherapy by quantitative in situ image analysis and fluorescent in situ 5;-nuclease assay (FISNA). Despite plasma virus suppression, a fraction of tonsil cells harbored pro-viral DNA for up to 1 year. A fourfold to eightfold increase in CD8+ T cells in tissue compared with seronegative controls and an increased frequency of CD1a+ dendritic cells prior to HAART reached control levels at week 56. The frequency of IFN-gamma expressing cells was 10-to 15-fold higher than controls before therapy and was comparable with findings in seronegative controls by week 56. Elevated baseline expression of IL-1alpha and IL-1beta was reduced by week 4 but IL-1alpha levels remained elevated in 1 of 3 patients at week 56. These findings suggest that with effective viral suppression the immune system in tissue may return to a more resting state.

Antiretroviral Therapy, Highly Active↗
PubMed2000

Sexual cooperation and conflict in butterflies: a male-transferred anti-aphrodisiac reduces harassment of recently mated females.

Sexual selection theory predicts that the different selection pressures on males and females result in sexual conflict. However, in some instances males and females share a common interest which could lead to sexual cooperation. In the pierid butterfly Pieris napi the male and the recently mated female share a common interest in reducing female harassment by other males soon after mating. Here we show that P. napi males transfer an anti-aphrodisiac to the female at mating, methyl-salicylate (MeS), which is a volatile substance which mated females emit when courted and which makes males quickly abandon them. A 13C-labelling experiment demonstrated that only males synthesize MeS. The effect of this antiaphrodisiac is so strong that most males will refrain from mating with virgin females to whom MeS has been artificially applied. In P. napi, males also transfer nutrients to females at mating. This increases female fecundity and longevity and so females benefit from remating. Hence, sexual cooperation gradually turns to conflict. Future research is required to reveal which sex controls the gradual decrease in the MeS titre which is necessary for allowing mated females to regain attractiveness and remate.

Animals↗
PubMed2000

Cysteines involved in radical generation and catalysis of class III anaerobic ribonucleotide reductase. A protein engineering study of bacteriophage T4 NrdD.

Class III ribonucleotide reductase (RNR) is an anaerobic glycyl radical enzyme that catalyzes the reduction of ribonucleotides to deoxyribonucleotides. We have investigated the importance in the reaction mechanism of nine conserved cysteine residues in class III RNR from bacteriophage T4. By using site-directed mutagenesis, we show that two of the cysteines, Cys-79 and Cys-290, are directly involved in the reaction mechanism. Based on the positioning of these two residues in the active site region of the known three-dimensional structure of the phage T4 enzyme, and their structural equivalence to two cysteine residues in the active site region of the aerobic class I RNR, we suggest that Cys-290 participates in the reaction mechanism by forming a transient thiyl radical and that Cys-79 participates in the actual reduction of the substrate. Our results provide strong experimental evidence for a similar radical-based reaction mechanism in all classes of RNR but also identify important differences between class III RNR and the other classes of RNR as regards the reduction per se. We also identify a cluster of four cysteines (Cys-543, Cys-546, Cys-561, and Cys-564) in the C-terminal part of the class III enzyme, which are essential for formation of the glycyl radical. These cysteines make up a CX(2)C-CX(2)C motif in the vicinity of the stable radical at Gly-580. We propose that the four cysteines are involved in radical transfer between Gly-580 and the cofactor S-adenosylmethionine of the activating NrdG enzyme needed for glycyl radical generation.

Bacterial Proteins↗
PubMed2000

Allosteric regulation of the class III anaerobic ribonucleotide reductase from bacteriophage T4.

Ribonucleotide reductase (RNR) is an essential enzyme in all organisms. It provides precursors for DNA synthesis by reducing all four ribonucleotides to deoxyribonucleotides. The overall activity and the substrate specificity of RNR are allosterically regulated by deoxyribonucleoside triphosphates and ATP, thereby providing balanced dNTP pools. We have characterized the allosteric regulation of the class III RNR from bacteriophage T4. Our results show that the T4 enzyme has a single type of allosteric site to which dGTP, dTTP, dATP, and ATP bind competitively. The dissociation constants are in the micromolar range, except for ATP, which has a dissociation constant in the millimolar range. ATP and dATP are positive effectors for CTP reduction, dGTP is a positive effector for ATP reduction, and dTTP is a positive effector for GTP reduction. dATP is not a general negative allosteric effector. These effects are similar to the allosteric regulation of class Ib and class II RNRs, and to the class Ia RNR of bacteriophage T4, but differ from that of the class III RNRs from the host bacterium Escherichia coli and from Lactococcus lactis. The relative rate of reduction of the four substrates was measured simultaneously in a mixed-substrate assay, which mimics the physiological situation and illustrates the interplay between the different effectors in vivo. Surprisingly, we did not observe any significant UTP reduction under the conditions used. Balancing of the pyrimidine deoxyribonucleotide pools may be achieved via the dCMP deaminase and dCMP hydroxymethylase pathways.

Adenosine Triphosphate↗
PubMed2000

[Risk of early therapeutic failure after prostatectomy is relatively great. Tumor grade and preoperative serum level of PSA are significant prognostic variables].

Prostate cancer is the most common malignancy among males in the West. Any reduction in mortality would require early detection of cases in which curative treatment is possible. From 1994 through 1998, 105 patients with clinically localised T1-T2 tumours were operated via radical prostatectomy at Karolinska sjukhuset in Stockholm. Three patients were lost to follow-up. We obtained clinical data from patients' records and used pathologist reviews to characterise tumours regarding grade and histopathological stage. We used PSA in serum as a surrogate endpoint, with a value above 0.6 ng/ml designated as treatment failure. Outcome was examined with respect to tumour grade, histopathological stage and pre-operative PSA level. Altogether 22% of patients showed PSA failure during follow-up. No mortality due to prostate cancer was recorded. We found that both tumour grade and pre-operative serum PSA level correlated well with treatment failure (P < 0.01). Our findings illustrate the diagnostic difficulties involved, since a relatively large percentage of patients were registered for treatment failure shortly after radical prostatectomy.

Follow-Up Studies↗
PubMed2000

Precursor B cell receptor-dependent B cell proliferation and differentiation does not require the bone marrow or fetal liver environment.

The capacity of precursor B (pre-B) I cells from fetal liver and bone marrow to proliferate and differentiate into surface immunoglobulin-positive immature B cells in vitro was analyzed. Both fetal liver- and bone marrow-derived progenitors do so in a pre-B cell receptor (pre-BCR)-dependent manner in tissue culture medium alone, without addition of other cells or cytokines. Approximately 20% of the initial pre-B I cells enter more than one division. Analyses at the single-cell level show that approximately 15% divide two to five times. Coculture of pre-B I cells with stromal cells did not enhance proliferation or differentiation, whereas the presence of interleukin 7, especially in combination with stromal cells, resulted mainly in the expansion of pre-B I cells and prevented their further differentiation. Thus, the environment of fetal liver or bone marrow is not required for the pre-BCR to exert its function, which is to select and expand cells that have undergone an inframe V(H)-D(H)J(H) rearrangement that produces a pre-BCR-compatible muH chain. It appears unlikely that a ligand for the pre-BCR drives this pre-B cell proliferation.

Animals↗
PubMed2000

The B cell receptor, but not the pre-B cell receptor, mediates arrest of B cell differentiation.

B cell development in organ cultures of fetal liver from mice at day 14 of gestation resembles in kinetics and cell numbers generated the one observed in vivo. This development in vitro can be blocked by an IL-7 receptor-specific monoclonal antibody. Monoclonal antibodies specific for the pre-B cell receptor, i. e. for VpreB, lambda5, or muH chains, do not perturb B cell development in these organ cultures up to and including the CD25+ small pre-BII cell stage. However, muH chain-specific antibodies inhibit the appearance of the subsequent surface IgM+ immature B cells. In organ cultures of muH chain allotype heterozygous (muHa x muHb)F1 fetal livers a dose-dependent inhibition by allotype-specific monoclonal antibodies of sIgM+ immature B cells expressing the corresponding, but not the other, allotype was observed. By combining cell sorting with limiting dilution analysis of lipopolysaccharide-reactive cells, the probable target cell of this muH chain-specific inhibition was identified as an IgM+, CD23-immature B cell. Hence, engagement of the pre-B cell receptor by specific antibodies does not influence B cell development, while engagement of the B cell receptor on immature B cells does.

Animals↗
PubMed2000

Cardiovascular responses to cold-water immersions of the forearm and face, and their relationship to apnoea.

Apnoea as well as cold stimulation of the face or the extremities elicits marked cardiovascular reflexes in humans. The purpose of this study was to investigate whether forearm immersion in cold water has any effect on the cardiovascular responses to face immersion and apnoea. We recorded cardiovascular responses to coldwater immersions of the forearm and face in 19 (part I) and 23 subjects (part II). The experimental protocol was divided in two parts, each part containing four tests: I1, forearm immersion during eupnoea; I2, face immersion during eupnoea; I3, forearm and face immersion during eupnoea; I4, face immersion during apnoea; II1, apnoea without immersion; II2, forearm immersion during apnoea; II3, face immersion during apnoea; and II4, forearm and face immersion during apnoea. The water temperature was 9-11 degrees C. Cold-water immersion of either the forearm or face was enough to elicit the most pronounced thermoregulatory vasoconstriction during both eupnoea and apnoea. During eupnoea, heart rate responses to forearm immersion (3% increase) and face immersion (9% decrease) were additive during concurrent stimulation (3% decrease). During apnoea, the heart rate responses were not affected by the forearm immersion. The oxygen-conserving diving response seems to dominate over thermoregulatory responses in the threat of asphyxia. During breathing, however, the diving response serves no purpose and does not set thermoregulatory adjustments aside.

Adult↗