Biomedical subjects

B Lundgren

Publications and source records attributed to B Lundgren.

At least 73 records · Page 4Linked to original sources

PubMed1993

Multiple genes encode the major surface glycoprotein of Pneumocystis carinii.

The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this antigen is a good candidate for development as a vaccine to prevent or control P. carinii infection. We have cloned and sequenced seven related but unique genes encoding the major surface glycoprotein of rat P. carinii. Partial amino acid sequencing confirmed the identity of these genes. Based on Southern blot studies using chromosomal or restricted DNA, the major surface glycoproteins are the products of a multicopy family of genes. The predicted protein has an M(r) of approximately 123,000, is relatively rich in cysteine residues (5.5%) that are very strongly conserved, and contains a well conserved hydrophobic region at the carboxyl terminus. The presence of multiple related msg genes encoding the major surface glycoprotein of P. carinii suggests that antigenic variation is a possible mechanism for evading host defenses. Further characterization of this family of genes should allow the development of novel approaches to the control of this pathogen.

Amino Acid Sequence↗

PubMed1993

Antibody response to a major human Pneumocystis carinii surface antigen in patients without evidence of immunosuppression and in patients with suspected atypical pneumonia.

IgG and IgM antibodies to a purified human Pneumocystis carinii surface antigen (gp95) were measured in 694 serum specimens from two different population groups using an EIA technique. In a population of 441 patients with no evidence of immunosuppression, the percentage of persons positive for IgG antibodies to gp95 was significantly lower in the age group 1 to 9 years (30%, 23/77) compared to persons 10 to 19 years old (56%, 49/88). In the age group 1 to 14 years there was a significant correlation between the percentage of persons with IgG antibodies to gp95 and age. In 106 consecutive patients under evaluation due to atypical pneumonia, 76 patients showed no change in the titre of antibodies to Legionella spp. or Mycoplasma pneumoniae in two consecutive serum samples. Three of these 76 patients (4%) demonstrated an increase in the level of IgG antibodies to gp95 in the paired samples. One of these patients had a verified Pneumocystis carinii pneumonia, and the two others were elderly men in whom no microbiological diagnosis of the pneumonia was established. Thus, it is concluded that IgG antibodies to gp95 develop in the majority of nonimmunosuppressed persons before the age of 13. Furthermore, Pneumocystis carinii pneumonia should be considered in the differential diagnosis in patients suspected of having atypical pneumonia.

Adolescent↗

PubMed1993

Salvage trial of trimetrexate-leucovorin for the treatment of cerebral toxoplasmosis in patients with AIDS.

The clinical efficacy of trimetrexate, a dihydrofolate reductase inhibitor with potent in vitro antitoxoplasma activity, was assessed in 9 sulfonamide-intolerant patients with AIDS and biopsy-proven cerebral toxoplasmosis. The 9 patients were treated for 28-149 days with trimetrexate (30-280 mg/m2/day) plus leucovorin (20-90 mg/m2 every 6 h). Radiographic responses were documented in 8 patients, and clinical responses in 5 patients. Despite continued therapy, all patients deteriorated clinically and radiographically within 13-109 days of their initial improvement. Trimetrexate at very high doses for extended periods was not associated with serious toxicity. Trimetrexate alone had dramatic but transient activity in sulfonamide-intolerant patients and thus is not adequate as single-agent therapy for AIDS-associated toxoplasmosis.

Acquired Immunodeficiency Syndrome↗

PubMed1993

IgM response to a human Pneumocystis carinii surface antigen in HIV-infected patients with pulmonary symptoms.

We have developed an ELISA to detect IgM antibodies to a major human Pneumocystis carinii surface antigen (gp95), and investigated the IgM response in 128 HIV-infected patients who underwent bronchoscopy for evaluation of pulmonary symptoms. Only 5 (4%) patients had IgM antibodies to P. carinii gp95. Four of the 5 patients with IgM antibodies also had IgG antibodies to gp95 and microbiologically proven P. carinii pneumonia (PCP). In 76/128 patients for whom serial samples were available, changes in antibody response were determined. In 3 patients we demonstrated an increase in IgM antibody response to gp95. These patients also showed an increase in IgG antibodies to gp95 and had microbiologically proven PCP. Prior to the development of the IgM response, IgG antibodies to gp95 were detectable in all 3 patients. Thus, HIV-infected patients with PCP seldom produce IgM antibodies to the major human P. carinii surface antigen. The increase in IgM response during the course of PCP observed in 3 patients suggests either reinfection with a new strain, or antigenic drift of an already acquired strain of P. carinii.

AIDS-Related Opportunistic Infections↗

PubMed1993

Effects of perfluoro fatty acids on peroxisome proliferation and mitochondrial size in mouse liver: dose and time factors and effect of chain length.

1. Male mice were fed a diet containing perfluoro fatty acids of varying chain length (i.e. perfluoroacetic, -butyric, -octanoic and -decanoic acids) at different doses (0.02 or 0.1% w/w of diet) for different periods of time (2-10 days), and effects on liver weight, hepatic mitochondrial protein and hepatic peroxisomal palmitoyl-CoA oxidation, lauroyl-CoA oxidase and catalase were monitored. 2. The greatest effects were obtained with perfluoro-octanoic and perfluoro decanoic acids, while perfluoro acetic acid was inactive. The effects with 0.02% w/w of diet perfluoro-octanoic acid were at least as great as those observed with 0.1%. A more detailed dose-response investigation focused on perfluoro-octanoic acid revealed that maximal effects with this substance could be obtained with a dietary dose of 0.01% for 10 days and that significant changes were also observed with 0.001%. 3. Maximal effects with 0.02% w/w of diet perfluoro-octanoic acid were attained after 6-10 days of feeding. 4. As with other peroxisome proliferators, perfluoro fatty acids increase mouse hepatic peroxisomal fatty acid beta-oxidation more extensively than they increase catalase, thus increasing hepatic oxidative stress. 5. As with other peroxisome proliferators, perfluoro fatty acids increase mouse liver mitochondrial protein. This effect is due primarily to a redistribution of mitochondria from the nuclear to the mitochondrial fraction, caused by an apparent decrease in the mean size of hepatic mitochondria after treatment.

Acyl-CoA Oxidase↗

PubMed1993

Formation of free radicals during phacoemulsification.

During phacoemulsification cavitation bubbles are formed. These bubbles are believed to be one source of damage to corneal endothelium seen after phacoemulsification. Free radicals are induced whenever cavitation bubbles implode. The aim of this study was to confirm the initiation of free radicals by phacoemulsification and to correlate the power of ultrasound in the phacoemulsification process to the amount of free radicals formed, using both in vitro and in vivo techniques. The formation of free radicals was determined by adding luminol to a buffer and measuring the chemoluminescence in vitro and in rabbit eyes (Lumacounter 2080 or a single-photon-counting apparatus) during phacoemulsification. The data obtained show that free radicals are formed during phacoemulsification and that the amount of free radicals correlates with the power of ultrasound. Furthermore, the radical formation could be inhibited by the radical scavengers SOD, Healon and Healon GV. These results were achieved both in vitro in the test tube and in vivo in rabbit eyes. By showing that the addition of SOD to the irrigation buffer during phacoemulsification decreases the corneal endothelial cell damage, we show that free radicals could have a role in postoperative complications seen clinically.

Animals↗

PubMed1993

Effects of selenium deficiency on xenobiotic-metabolizing and other enzymes in rat liver.

The present study was undertaken to characterize effects of selenium (Se) deficiency on 16 enzymes recovered in either one or more of the subcellular fractions of rat liver (as a basis for future studies on the mechanisms underlying the observed changes). Male rats were fed a Torula-yeast based diet with 0.23 mg Se/kg or the same diet with 0.009 mg Se/kg, from weaning and for 10 weeks. Statistically significant effects of Se deficiency were the following: Se-dependent glutathione peroxidase decreased to 0.14% of the Se-adequate controls, while cytosolic glutathione transferase increased 3-fold in Se deficiency when CDNB was the substrate, but decreased significantly when trans-stilbene oxide (diagnostic for subunit 4) was used as the substrate. Cytosolic DT-diaphorase increased about 7-fold in Se deficiency. Further, DT-diaphorase in the microsomal fraction was also significantly increased in Se deficiency, as were the microsomal and mitochondrial epoxide hydrolases and microsomal glutathione transferase. Furthermore, increased activity of the peroxisomal marker enzyme catalase (P < 0.05) was noted in Se-deficient rats. It is our working hypothesis that changes in enzyme activities in Se deficiency are mainly due to changed levels of endogenously generated metabolites or altered functions of endocrine tissues.

Animals↗

PubMed1993

Glycosylation of the major human Pneumocystis carinii surface antigen.

It has recently been shown that the major rat P. carinii surface antigen is important for initial host-organism attachment, possibly through binding to fibronectin, mannose-binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook this study to characterize the glycosylation of the major human P. carinii surface glycoprotein (gp95). We have used purified gp95 as a source of antigen, and in lectin binding and deglycosylation studies it was found that approximately 9% of gp95 consists of N-linked carbohydrates of mainly high-mannose and bisected complex-type glycans. Using a polyclonal antibody raised against purified gp95 and crossed affinoimmunoelectrophoresis and the lectins Con A and WGA, gp95 exhibited carbohydrate-dependent microheterogeneity. We therefore suggest that gp95 is composed of subtypes which differ in N-linked glycosylation.

Antigens, Fungal↗

PubMed1992

The involvement of selenium in peroxisome proliferation caused by dietary administration of clofibrate to rats.

The effects of dietary treatment with clofibrate (0.5% w/w for 10 days) on the livers of selenium-deficient male rats were examined. The peroxisome proliferation (as determined by electron microscopy) in the livers of selenium-deficient animals was much less pronounced than in the case of selenium-adequate rats and no increase in peroxisomal fatty acid beta-oxidation (assayed both as antimycin-insensitive palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity) was observed in the deficient animals. On the other hand, in selenium-deficient rats clofibrate caused increases in the specific activity of microsomal lauric acid omega- and omega-1-hydroxylation and an apparent change in mitochondrial size, seen as a redistribution of mitochondria from the 600 x g(av) pellet to the 10,000 x g(av) pellet, which were approximately 50% as great as the corresponding effects on control animals. Obviously, then, these three different effects of clofibrate are not strictly coupled and may involve at least partially distinct underlying mechanisms. Initial experiments demonstrated that peroxisome proliferation could be obtained by exposing primary hepatocyte cultures derived from selenium-deficient rats to clofibric acid (an in vivo hydrolysis product of clofibrate which is the proximate peroxisome proliferator), nafenopin or mono(2-ethylhexyl)phthalate. This finding suggests that selenium deficiency does not have a direct influence on the basic process(es) underlying peroxisome proliferation, but rather has indirect effects, influencing, for example, the pharmacokinetics of clofibrate and/or hormonal factors.

Animals↗

PubMed1992

Breast carcinoma growth rate described by mammographic doubling time and S-phase fraction. Correlations to clinical and histopathologic factors in a screened population.

BACKGROUND: In a retrospective study, correlations among mammographic doubling times (DT), clinicopathologic prognostic factors, and cytometric predictors were examined. METHODS: One hundred fifty-eight patients with the possibility to calculate mammographic tumor DT were selected and the tumors were histologically reexamined and flow cytometric analysis for ploidy and S-phase fraction (SPF) was performed. RESULTS: The tumors were Stage I in 68%, and 45% were detected by mammographic screening. DT ranged from 0.6 months to an indefinite time (median, 9.0 months). Short DT was significantly correlated to large tumor size (P = 0.01) and advanced pathologic tumor stage (P = 0.016), but there was no correlation between DT and histologic grade. Ploidy analysis indicated that there were 57% aneuploid and 7% tetraploid tumors. There was a significant overrepresentation of euploid tumors among tumors smaller than 10 mm (P = 0.02). Ploidy was correlated to histologic grade (P less than 0.001) and DT (P = 0.009). SPF was calculated in 122 cases. SPF correlated significantly with pathologic stage (P = 0.002), tumor size (P = 0.037), histologic grade (P = 0.001), the presence of axillary lymph node metastases (P = 0.046), DT (P = 0.02), and DNA ploidy (P less than 0.001). Compared with interval carcinoma, screening-detected carcinoma showed favorable characteristics concerning size, stage, DT, ploidy, and SPF but not regarding histologic grade and axillary lymph node metastases. CONCLUSIONS: DT shows great variations. Factors related to tumor biology (i.e., DT, DNA ploidy, and SPF) are strongly correlated with one another, but they have no correlation with axillary lymph node metastases. Cancer detected by screening is discovered at an early stage and shows favorable characteristics concerning DT, ploidy, and SPF.

Adult↗

PubMed1992

Mammographic growth rate, DNA ploidy, and S-phase fraction analysis in breast carcinoma. A prognostic evaluation in a screened population.

BACKGROUND: The authors examined prognostic factors in 158 cases of breast carcinoma with known mammographic tumor volume doubling times (DT). METHODS: The tumors were retrospectively reexamined histologically and flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) was performed on archival paraffin-embedded material in each case. Life tables and Cox multivariate analyses were used for statistical evaluation of prognostic factors. RESULTS: In univariate analysis of survival data, clinical and pathologic stage, histologic grade, the presence of axillary lymph node metastases, and SPF were significant prognostic predictors, but mammographic DT and DNA ploidy were not. SPF also contributed prognostic information in the subgroup of carcinoma cases detected by screening. In a Cox multivariate analysis, SPF, the presence of axillary lymph node metastases, and Stage II-III disease (as opposed to Stage I disease) were independent significant predictors of survival. In univariate analyses of distant disease-free survival, clinical and pathologic stage, tumor size, histologic grade, the presence of involved axillary nodes, DT, and SPF all were significant prognostic factors. CONCLUSIONS: SPF, stage, and lymph node status were important prognostic factors in this patient material with predominantly small and node-negative breast carcinomas, whereas DNA ploidy and mammographic DT provided less prognostic information. The prognosis of carcinoma detected during screening did not differ significantly from that of breast carcinoma discovered otherwise in this selected patient group.

Adult↗

PubMed1992

Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver.

Male mice were exposed via their diet to perfluoro fatty acids of various chain-lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial protein content, microsomal contents of cytochromes P450 and b5, NADPH-cytochrome P450 reductase activity [measured as NADPH-cytochrome c reductase (EC 1.6.2.3)], microsomal and cytosolic epoxide hydrolase (EC 3.3.2.3) activities, cytosolic DT-diaphorase (EC 1.6.99.2), glutathione transferase (EC 2.5.1.18), glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities, and levels of thiobarbituric acid-reactive material (as an indicator of lipid peroxidation) in the mitochondrial subfraction. The most dramatic changes observed were a 5-9-fold increase in mitochondrial protein, a 3-6-fold increase in the microsomal content of cytochrome P450, a 3-10-fold increase in cytosolic DT-diaphorase activity, an approximately 2-fold increase in cytosolic epoxide hydrolase activity and as much as a 60% decrease in the level of thiobarbituric acid-reactive compounds in the mitochondrial fraction. Smaller increases in microsomal epoxide hydrolase activity and decreases in cytosolic glutathione peroxidase activity were also observed. Of the perfluoro fatty acids tested, perfluorooctanoic acid caused the largest changes in the parameters examined here. Dietary exposure of mice to a 0.02% dose of this substance for 10 days results in a maximal or near-maximal effect in most cases.

Animals↗

PubMed1992

Is the cytosolic catalase induced by peroxisome proliferators in mouse liver on its way to the peroxisomes?

Dietary treatment of male C57B1/6 mice with clofibrate, nafenopin or WY-14.643 resulted in a modest (at most 2-fold) increase in the total catalase activity in the whole homogenate and mitochondrial fraction prepared from the livers of these animals. On the other hand, the catalase activity recovered in the cytosolic fraction was increased 12- to 18-fold, i.e. 30-35% of the total catalase activity in the hepatic homogenate was present in the high-speed supernatant fraction after treatment with these peroxisome proliferators. A study of the time course of the changes in peroxisomal and cytosolic catalase activities demonstrated that the peroxisomal activity both increased upon initiation of exposure and decreased after termination of treatment several days after the increase and decrease, respectively, in the corresponding cytosolic activity. This finding suggests that the cytosolic catalase may be on its way to incorporation into peroxisomes.

Animals↗

PubMed1992

Effects of dietary treatment with 11 dicarboxylic acids, diethylcarboxylic esters and fatty acids on peroxisomal fatty acid beta-oxidation, epoxide hydrolases and lauric acid omega-hydroxylation in mouse liver.

C57B1/6 male mice were exposed through their diet to 11 dicarboxylic acids, carboxylic acids and diethyldicarboxylesters for 10 days. For the diacids and diethylesters this treatment resulted in a chain length-dependent induction of lauryl-CoA oxidase and cyanide-insensitive palmitoyl-CoA oxidation activities. A chain length of 12 carbon atoms or more seemed to be necessary for induction of these two activities. In addition, the same chain length dependence was observed for induction of lauric acid omega + omega-1 hydroxylase activity and increase in the protein content of the mitochondrial fraction. Treatment with two "natural" fatty acids, i.e. lauric and palmitic acid gave no effect at all on these various parameters. In no case was induction of cytosolic and mitochondrial epoxide hydrolase activities observed. Instead, a slight decrease in these activities was observed after administration of diacids with a chain length of 4-8 carbon atoms, whereas microsomal epoxide hydrolase activity was concurrently induced.

Animals↗

PubMed1992

Perfluorooctanoic acid has persistent effects on peroxisome proliferation and related parameters in mouse liver.

Male C57Bl/6 mice were treated for 5 days with 0.05% perfluorooctanoic acid (PFOA) in their diet. This treatment resulted in a potent induction of peroxisomal fatty acid beta-oxidation in the liver. In order to investigate recovery from treatment with PFOA, mice were given normal laboratory chow for up to 20 days after termination of PFOA administration. It was established that the activities of peroxisomal lauoryl-CoA oxidase and palmitoyl-CoA oxidation were still elevated 2-3 weeks after termination of treatment. The catalase activity recovered in the cytosolic fraction was also still significantly elevated after 20 days with normal laboratory chow. Furthermore, the protein content of the mitochondrial fraction was increased by PFOA and had not returned to control level at the end of the recovery period. Perfluorooctanoic acid also caused a persistent effect in omega hydroxylation of lauric acid (cytochrome P-452). The activities of cytosolic DT-diaphorase and glutathione transferase were also enhanced by PFOA. However, these two enzymes recovered relatively rapidly from the treatment (2-20 days). This study reveals two different patterns of recovery from PFOA treatment, one involving parameters that recovered completely, or almost completely, from PFOA treatment after 20 days and another involving parameters that were still elevated at the end of the recovery period.

Acyl-CoA Oxidase↗

PubMed1992

Inflammatory response in the rabbit eye after intraocular implantation with poly(methyl methacrylate) and heparin surface modified intraocular lenses.

Early inflammatory responses in rabbit eyes after anterior chamber implantation with poly(methyl methacrylate) (PMMA) and heparin surface modified intraocular lenses (IOLs) and after cataract extraction and implantation with PMMA and heparin surface modified intraocular lenses (IOLs) were investigated between 1 and 30 days postoperatively. The number of white blood cells in the aqueous humor, the distribution of white blood cell subsets, and the interleukin-1 (IL-1b) levels were studied. At one day postoperatively, there was a significantly smaller number of white blood cells in eyes with heparin surface modified IOLs than in eyes with PMMA IOLs after both anterior chamber implantation and cataract surgery and capsular bag implantation. At one day postoperatively, 87% of the cell population in eyes with PMMA IOLs were neutrophilic granulocytes. Two days later the neutrophilic granulocytes had decreased to 13% and at seven days they were gone. At 14 days the frequency was 7% and at 30 days it was 27%. The fraction of monocytes/macrophages in the cell population was 9% (day 1), 79% (day 3), 94% (day 7), 81% (day 14), and 72% (day 30). The fraction of lymphocytes was low throughout the test period (1% to 10%). The percentages were almost the same in eyes with heparin surface modified IOLs and there was no significant difference in the distribution of white blood cell subsets between the two lens materials. The IL-1 was not detected in any of the samples (day 3, day 7, and day 30). Inactivated macrophages and/or levels under detection limits could be the reason.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Cellular reaction following cataract surgery with implantation of the heparin-surface-modified intraocular lens in rabbits with experimental uveitis.

The inflammatory response after cataract surgery and intraocular lens (IOL) implantation was studied in rabbits with endotoxin-induced uveitis. On days 1, 3, 7, 14, and 30 postoperatively the rabbits were sacrificed and the number of white blood cells in the aqueous humor and cellular deposits on the IOLs were estimated. On days 14 and 30 the rabbits also had slitlamp examination to study the clinical outcome of the surgery. At day 1 after lens extraction and IOL implantation, the number of white blood cells in the aqueous humor was significantly lower (P < .05) in eyes with heparin-surface-modified (HSM) IOLs (795.2 +/- 262.9; mean +/- SEM) than in eyes with poly(methyl methacrylate) (PMMA) lenses (1386.5 +/- 247.9). No differences were seen at day 3, 7, 14, or 30 postoperatively. The choice of IOL material had no effect on the amount of cell deposits on the IOL surface or on clinical parameters such as anterior synechias, posterior synechias, fibrosis, and posterior capsular opacification. There was a trend toward a greater number of cellular deposits on the PMMA lenses, but this was not statistically significant. This study provides further evidence of improved biocompatibility of the HSM PMMA lens, as demonstrated by a decreased acute inflammatory response.

Acute Disease↗

PubMed1992

Fibrinous reaction on implanted intraocular lenses. A comparison of conventional PMMA and heparin surface modified lenses.

We studied the fibrinous reaction after intraocular lens (IOL) implantation in the posterior chamber of cynomolgus monkeys. In 50% of the eyes, we implanted an IOL made of conventional poly-(methyl methacrylate) (PMMA); in the remaining eyes we implanted a PMMA IOL with a heparin modified surface. Two, 4, 8, and 18 weeks after surgery the eyes were examined by slitlamp for fibrinous reactions on and around the IOL surface. At weeks 4, 8, and 18 there was a marked decrease in fibrinous reaction in the eyes with a heparin surface modified IOL. The results of this study accord with earlier findings that heparin surface modification improves the biocompatibility of the IOL.

Animals↗