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Biomedical subjects

C Andersson

Publications and source records attributed to C Andersson.

At least 127 records · Page 7Linked to original sources

Interleukin 1 expression is inducible by nerve growth factor in PC12 pheochromocytoma cells.

Expression of the cytokine interleukin 1 alpha (IL-1 alpha) was demonstrated in the rat PC12 pheochromocytoma cell line by (i) immunohistochemistry using rabbit polyclonal antisera raised against the recombinant murine IL-1 alpha, (ii) an ELISA, and (iii) a specific cell conversion bioassay based on the use of LBRM33-1A5 cells. IL-1 alpha mRNA was demonstrated in the PC12 cells, by PCR amplification. Constitutive expression of IL-1 alpha in PC12 cells was demonstrated in all experiments, although the cellular levels of IL-1 alpha-like immunoreactivity varied. The expression of IL-1 alpha, as studied at the mRNA level, was inducible by mouse nerve growth factor (7S NGF), and the gene product level was inducible in a dose- and time-dependent fashion by 7S NGF. The maximum induction corresponds to a 600% increase in IL-1 alpha-like immunoreactivity above the expression level found in noninduced cells and occurred after a 3-day incubation of the cells with NGF at 0.75 micrograms/ml of culture medium. The significance of the ability of NGF to induce IL-1 expression lies in the fact that IL-1 itself also acts as a growth factor that promotes glial proliferation and, even more importantly, IL-1 itself induces the expression of NGF at peripheral nerve injury [Lindholm, D., Heumann, R., Meyer, M. & Thoenen, H. (1987) Nature (London) 330, 658-659].

Animals↗

Studies on the activity and activation of rat liver microsomal glutathione transferase with a series of glutathione analogues.

The substrate specificity of rat liver microsomal glutathione transferase toward glutathione has been examined in a systematic manner. Out of a glycyl-modified and eight gamma-glutamyl-modified glutathione analogues, it was found that four (glutaryl-L-Cys-Gly, alpha-L-Glu-L-Cys-Gly, alpha-D-Glu-L-Cys-Gly, and gamma-L-Glu-L-Cys-beta-Ala) function as substrates. The kinetic parameters for three of these substrates (the alpha-D-Glu-L-Cys-Gly analogue gave very low activity) were compared with those of GSH with both unactivated and the N-ethylmaleimide-activated microsomal glutathione transferase. The alpha-L-Glu-L-Cys-Gly analogue is similar to GSH in that it has a higher kcat (6.9 versus 0.6 s-1) value with the activated enzyme compared with the unactivated enzyme but displays a high Km (6 versus 11 mM) with both forms. Glutaryl-L-Cys-Gly, in contrast, exhibited a similar kcat (8.9 versus 6.7 s-1) with the N-ethylmaleimide-treated enzyme but retains a higher Km value (50 versus 15 mM). Thus, the alpha-amino group of the glutamyl residue in GSH is important for the activity of the activated microsomal glutathione transferase. These observations were quantitated by analyzing the changes in the Gibbs free energy of binding calculated from the changes in kcat/Km values, comparing the analogues to GSH and each other. It is estimated that the binding energy of the alpha-amino group of the glutamyl residue in GSH contributes 9.7 kJ/mol to catalysis by the activated enzyme, whereas the corresponding value for the unactivated enzyme is 3.2 kJ/mol. The importance of the acidic functions in glutathione is also evident as shown by the lack of activity with 4-aminobutyric acid-L-Cys-Gly and the low kcat/Km values with gamma-L-Glu-L-Cys-beta-Ala (0.03 and 0.01 mM-1s-1 for unactivated and activated enzyme, respectively). Utilization of binding energy from a correctly positioned carboxyl group in the glycine residue (10 and 17 kJ/mol for unactivated and activated enzyme, respectively) therefore also appears to be required for optimal activity and activation. A conformational change in the microsomal glutathione transferase upon treatment with N-ethylmaleimide or trypsin, which allows utilization of binding energy from the alpha-amino group of GSH as well as the glycine carboxyl in catalysis, is suggested to account for at least part of the activation of the enzyme.

Amino Acid Sequence↗

Effects of indomethacin, cytokines, and cyclosporin A on tumor growth and the subsequent development of cancer cachexia.

C57BL/6J mice bearing a low or undifferentiated rapidly growing tumor were treated daily with either i.p. injections of the recombinant cytokines interleukin(IL)-1 alpha, IL-1 beta (21 ng/g), and tumor necrosis factor alpha (21 ng/g) or s.c. injections of cyclosporin A (60 micrograms/g) or indomethacin (1 micrograms/g). In some experiments, indomethacin was administered in the drinking water corresponding to the amount of s.c. injections. Survival and the time course of tumor growth and food and water intake were measured. The nutritional state (body composition) of the animals was registered at spontaneous death in the course of tumor disease. Indomethacin prolonged survival from 14 +/- 1 to 22 +/- 1 days in tumor-bearing mice when administered either in the drinking water or as s.c. injections. This effect, which was due to tumor growth inhibition, was equally effective irrespective of whether indomethacin was instituted on Day 1, 5, 7, or 9 following tumor implantation. Indomethacin did not inhibit tumor cell growth in vitro. Indomethacin-treated tumor-bearing mice were also less anorectic than untreated tumor-bearing mice, and their nutritional state, particularly lean body mass, was significantly improved by indomethacin at doses (1 micrograms/g) that did not influence the food intake or body composition in non-tumor-bearing mice. At spontaneous death, indomethacin-treated tumor-bearing mice had a significantly larger tumor burden when accounting for their degree of malnutrition as compared with untreated tumor bearers. Indomethacin did not decrease the elevation in hepatic concentrations of RNA seen in response to tumor progression. Adherent peritoneal macrophages from tumor-bearing mice had a lower prostaglandin E2 synthesis compared with macrophages from non-tumor-bearing controls in the basal state (1100 +/- 150 pg/10(6) cells versus 3700 +/- 922 pg/10(6) cells). Lipopolysaccharide stimulated macrophages from tumor-bearing mice to produce significantly more prostaglandin E2 in vitro compared with control macrophages (39,500 +/- 4208 pg/10(6) cells versus 12,500 +/- 4330 pg/10(6) cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cancer morbidity in nitrate fertilizer workers.

A cohort of 2,131 male nitrate fertilizer workers was evaluated for cancer morbidity from 1963 to 1986. No significant increase in total cancer, stomach cancer (5 actual vs 6.7 expected cases), or lung cancer (13 vs 13 expected) was found. On the other hand, 26 actual cases of prostate cancer were observed vs 16 expected cases (standardized morbidity ratio, SMR = 161; 95%, confidence interval, CI = 107-239). This risk increase however, was, not enhanced by applying at least a 10-year latency period. In a cohort of 1,148 male fertilizer workers who had never been exposed to nitrate, there was an increased incidence of lung cancer (SMR = 151,95% CI = 103-220) but not of stomach cancer or prostate cancer. There was no association between airborne nitrate exposure dose and total cancer, stomach cancer, lung cancer or prostate cancer, respectively.

Adult↗

Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice.

Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating [3H]raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Knee function after surgical or nonsurgical treatment of acute rupture of the anterior cruciate ligament: a randomized study with a long-term follow-up period.

One hundred fifty-six patients with a total rupture of the anterior cruciate ligament (ACL) were reexamined 41 to 80 months after injury. They were randomized to three treatment groups: (1) repair and augmentation of the ACL with an iliotibial strip, (2) repair without augmentation, and (3) nonsurgical ACL treatment. Associated injuries of menisci and other ligaments were treated in the same way for the three groups. Two-thirds of the patients in the nonsurgically treated group complained of instability and 17% had had a subsequent reconstruction of the ACL at the follow-up examination. The group treated with an augmented repair had a less abnormal laxity measured by a laxity-testing device. Sixty-three percent returned to competitive sports, as compared with 27% in the nonsurgical group and 32% in the only repair group. Relative strength of the quadriceps and hamstrings muscles were similar for all groups. The augmented-repair group had better hop tests, reflecting a superior stability, whereas running was not affected by treatment but was correlated with the activity level.

Adolescent↗

Chemical modification of rat liver microsomal glutathione transferase defines residues of importance for catalytic function.

Amino acid residues that are essential for the activity of rat liver microsomal glutathione transferase have been identified using chemical modification with various group-selective reagents. The enzyme reconstituted into phosphatidylcholine liposomes does not require stabilization with glutathione for activity (in contrast with the purified enzyme in detergent) and can thus be used for modification of active-site residues. Protection by the product analogue and inhibitor S-hexylglutathione was used as a criterion for specificity. It was shown that the histidine-selective reagent diethylpyrocarbonate inactivated the enzyme and that S-hexylglutathione partially protected against this inactivation. All three histidine residues in microsomal glutathione transferase could be modified, albeit at different rates. Inactivation of 90% of enzyme activity was achieved within the time period required for modification of the most reactive histidine, indicating the functional importance of this residue in catalysis. The arginine-selective reagents phenylglyoxal and 2,3-butanedione inhibited the enzyme, but the latter with very low efficiency; therefore no definitive assignment of arginine as essential for the activity of microsomal glutathione transferase can be made. The amino-group-selective reagents 2,4,6-trinitrobenzenesulphonate and pyridoxal 5'-phosphate inactivated the enzyme. Thus histidine residues and amino groups are suggested to be present in the active site of the microsomal glutathione transferase.

Animals↗

Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant.

To study whether exposure to low levels of vinyl chloride monomer (VCM) causes increased risk for cancer morbidity and death from ischemic heart disease, a cohort study was performed among 2,031 male workers at a polyvinyl chloride (PVC) processing plant who had been employed for at least 3 months during the period 1945-1980. An almost significantly increased total mortality (SMR = 116, 95% CI 99-136) was found. Deaths caused by violence or intoxication were significantly increased (SMR = 153, 95% CI 109-213), but not deaths from ischemic heart disease (SMR = 100, 95% CI 73-135). A significant increase in total cancer morbidity was observed (SMR = 128, 95% CI 101-161). Respiratory cancers were significantly increased (SMR = 213, 95% CI 127-346). Furthermore, six brain tumors (vs. 2.6 expected) were observed. This increase, however, was not significant (SMR = 229, 95% CI 84-498). No liver hemangiosarcoma was observed. Applying a latency period of greater than or equal to 10 years from start of employment did not change the risk patterns. There were no significant exposure-response associations between exposure estimates for VCM, asbestos, and plasticizers and cancer morbidity.

Adult↗

Increased degradation of albumin in cancer is not due to conformational or chemical modifications in the albumin molecule.

This study has evaluated whether increased albumin degradation in a tumor-bearing host is dependent on previously recognized chemical and environmental modifications in the albumin molecule as observed by others and ourselves. For the purpose, adult sarcoma-bearing mice with increased albumin degradation and electrophoretic heterogeneity were used and compared to freely fed (FF) or food restricted control animals. Food restricted control animals such as pair-fed (PF) and pair-weighed (PW) served to match the anorexia and malnutrition observed in tumor-bearing animals. The serum albumin concentration was decreased (P less than 0.05) in tumor-bearing animals (33 +/- 5 g/liter) compared to pair-fed (40 +/- 3), pair-weighed (41 +/- 4), and freely fed control mice (43 +/- 3). Isoelectric focusing of plasma between pH 3 and 10 and pH 4 and 6.5 confirmed a different isoelectric point for albumin in tumor-bearing animals compared to control animals. Albumin degradation was 33% higher in tumor-bearing mice compared to freely fed controls (P less than 0.01). Tumor-bearing animals had also significantly increased turnover of albumin compared to all control animals (0.13 +/- 0.022 mg/hr/g animal vs 0.05 +/- 0.008 mg/hr/g in PW; 0.08 +/- 0.009 in PF, and 0.09 +/- 0.007 in FF). The acidic fraction of albumin had a more rapid fractional turnover than the more basic components in both tumor-bearing and control animals. However, both the anodal and the cathodal albumin in tumor-bearing mice had a higher turnover compared with corresponding fractions of albumin from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Beta microseminoprotein is not a prostate-specific protein. Its identification in mucous glands and secretions.

Beta microseminoprotein (beta inhibin, PSP94), an unglycosylated protein of 94 amino acids with unknown function, is one of the predominating proteins in the secretion of the human prostate gland. In this work the authors have demonstrated that the expression of beta microseminoprotein is not restricted to the prostate and that the protein has a previously unrecognized widespread occurrence in the human body. According to radioimmunoassay, beta microseminoprotein immunoreactivity is present in many nonprostatic body fluids. The highest concentrations were found in secretions from the respiratory tract; in tracheobronchial fluid sometimes even at concentrations comparable to that in seminal plasma (about 1 g/l). Intermediate concentrations were found in gastric juice and some samples of secretion from the uterine cervix, whereas tears, saliva, pancreatic juice, bile, and mucus from the colon had low concentrations. According to gel chromatography, the molecular size of the beta microseminoprotein immunoreactivity present in tracheal fluid, gastric juice, and secretion from the uterine cervix did not differ from that of beta microseminoprotein in seminal plasma. The beta microseminoprotein immunoreactive component present in gastric juice had the same amino-terminal amino acid sequence as prostatic beta microseminoprotein (14 residues identified in material purified from gastric juice), providing further evidence for chemical identity of a nonprostatic beta microseminoprotein with the prostatic protein. Immunohistochemical staining with affinity-purified antibodies demonstrated the presence of beta microseminoprotein in many tissues, including the goblet cells in the tracheobronchial epithelium, tracheobronchial submucosal glands, certain mucosal cells in the antrum of the stomach, some glands of Brunner in the duodenum, and in parts of the mucosa of the colon. At least in the respiratory tract, the staining was localized to mucus-containing cells. beta microseminoprotein immunoreactivity also was localized to the cilia of the ciliated epithelium in the respiratory tract, the fallopian tubes, and the Gartner ducts of the uterine cervix. The pattern of tissue distribution of beta microseminoprotein found in this work indicates a connection of beta microseminoprotein with mucous secretions.

Adult↗

Instrumented testing for evaluation of sagittal knee laxity.

Seventy-one patients with untreated ruptures of the anterior cruciate ligament of at least four years' duration had their knee laxity examined with a laxity testing device. Twenty of the 71 patients were tested by two examiners independently. Another 30 patients without previous knee injury were chosen as a reference group and tested. Patients with anterior cruciate-deficient knees had significantly increased anterior and total laxity. If the testing procedure was altered, the laxity changed. Thus, an increase of knee flexion from 15 degrees to 25 degrees resulted in an increased anterior laxity. Changes in the amount and placement of the tibial load also affected laxity. Inter-examiner reproducibility was high if a standardized testing procedure was followed. Sensitivity was 92% if the difference in total laxity between involved and uninvolved knees was determined with a high tibial load (180 N), whereas specificity was 70%. Therefore, the laxity tester has disadvantages as a diagnostic tool, but it is still valuable for evaluation of anterior cruciate ligament ruptures and their treatment.

Adolescent↗

Rotational and translational movement features of the pelvis and thorax during adult human locomotion.

The kinematics of the pelvis and thorax are important in gait studies since their movement patterns are closely related to gait efficiency and 'smoothness' of locomotion. The purpose of this study was to identify features of normal gait patterns for later comparisons with pathological and developmental gait patterns. A two camera SELSPOT system interfaced with an HP1000 minicomputer was used to obtain three-dimensional kinematic/temporal data for the pelvis and thorax. Data from treadmill walking of eight adults were used for within subject (at different speeds) analyses. The analyses revealed a very complex pattern with a set of breakpoints which was consistent over all subjects. Some features were invariant over a range of walking speeds although the total range of motion changed considerably.

Adult↗

Interleukin-1 in adrenal chromaffin cells.

Interleukin-1, first identified as a macrophage factor of importance in infections and inflammation, is a protein with properties of an endogenous pyrogene and lymphocyte activating factor. Occurrence of interleukin-1-like immunoreactivity was demonstrated in the noradrenergic chromaffin cells of the rat and mouse adrenal gland by means of two antisera raised against synthetic peptides corresponding to the amino acid sequences 169-194 and 201-215 of the murine interleukin-1 precursor protein. These antisera also inhibited stimulation of interleukin-2 receptor expression by purified human interleukin-1. Reserpine, which is known to deplete catecholamines, also caused release of the interleukin-1-like immunoreactive material. The interleukin-1 content of the rat adrenal medulla was estimated by radioimmunoassay, and if released the adrenal interleukin-1 pool may result in plasma interleukin-1 levels of about 10(-12). The interleukin-1-immunoreactive material obtained from the rat adrenal gland was characterized as a trypsin-sensitive protein with a molecular weight in the range of 13,000-19,000. This protein fraction stimulated interleukin-2 receptor expression on human T-cells as earlier shown for interleukin-1.

Adrenal Medulla↗

Early arthroscopic evaluation of acute repair of the anterior cruciate ligament.

Follow-up arthroscopy was performed in 71 patients who had undergone primary repair of an acute rupture of the anterior cruciate ligament (ACL) after 6-19 months. An augmented repair was done on 61 patients and 10 patients had a nonaugmented repair. Based on the arthroscopic findings, the ACL repair was classified into three categories. Four years after the injury a clinical reexamination, including a laxity test using instrumentation and a standard knee-function test, was done on 66 patients. Arthroscopy revealed that 64 of the 71 patients (90%) had a defined ACL repair, although the repair was elongated in 37 patients. Seven patients with a nonfunctioning ACL repair had inferior knee function after 4 years. Arthroscopy also showed superficial cartilage lesions in 24 patients and meniscal pathology in 6 patients. Two patients with more advanced chondral lesions had inferior knee function. Treatment of meniscal injuries did not affect the long-term results.

Adult↗