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Biomedical subjects

R Andersson

Publications and source records attributed to R Andersson.

At least 253 records · Page 14Linked to original sources

Effect of biliary infection on common bile duct healing in the rat.

It has been postulated that biliary infection plays a role in bile duct stricture formation. The aim of this study was to verify this hypothesis and to evaluate the effect of biliary infection on common bile duct healing. A 3-mm longitudinal choledochotomy was performed in 120 rats and closed with a continuous 11/0 Ethilon suture. Common bile duct division with end-to-end anastomosis using interrupted 11/0 Ethilon sutures was performed in another 30 rats. Biliary infection was achieved in half of the animals with retrograde injection of living 046:K1:H31 strain Escherichia coli recovered from the rat colonic content. All rats with choledochotomy, including those with biliary infection, showed no bile leakage at the suture line, and the bursting pressure at the site of choledochotomy exceeded 40 mmHg as early as 24 h. Rats with common bile duct anastomosis alone showed no stricture formation for up to 6 months after operation. All rats with biliary sepsis developed complete occlusion at the anastomosis. On scanning electron microscopy, the biliary epithelium was well preserved in all rats. The study suggests that in rats with biliary sepsis the risk of bile leakage after primary closure of the common bile duct is negligible, but biliary infection may play a critical role in common bile duct stricture formation.

Anastomosis, Surgical↗

The effect of pancreatic islets on transplanted hepatocytes in the treatment of acute liver failure in rats.

We previously reported that co-transplantation of hepatocytes and islets of Langerhans in the spleen reduces the mortality rate after 90% hepatectomy in the rat. In the present study, we examined whether implantation of isolated hepatocytes into the pancreas is as efficient as co-transplantation of hepatocytes and islets in this respect. We found that cotransplantation of hepatocytes and islets into the renal subcapsule reduced the long-term (30-day) mortality rate after 90% hepatectomy from 100% to 36% (P less than 0.05) when performed the day before the hepatectomy. In contrast, there was no significant reduction of mortality when the hepatocytes were transplanted into the pancreas. The results show that a close proximity of transplanted pancreatic islets to the hepatocytes is of critical importance for the improved survival in acute liver failure.

Animals↗

Calcium signaling capacity of the CD11b/CD18 integrin on human neutrophils.

The CD11b/CD18 integrin is a major cell adhesion molecule of myelomonocytic cells. Exposure of human neutrophils in suspension to CD11b or CD18 monoclonal antibodies (mAbs)2 does not affect the resting level of cytosolic free Ca2+ in these cells; however, a subsequent cross-linking of either of these antibodies triggers a prompt and significant cytosolic-free Ca2+ transient lasting about 10 min. The rise in cytosolic-free Ca2+ (from 130 +/- 2 to 414 +/- 12 nM or 111 +/- 12 to 331 +/- 22 nM caused by cross-linking of CD11b or CD18 subunits, respectively) is due to both mobilization of Ca2+ from intracellular stores and influx of Ca2+ across the plasma membrane. Cross-linking of the common leukocyte antigen (CD45) did not alter the basal level of cytosolic free Ca2+. In accordance with other adherence-induced phenomena and with CD11/CD18-mediated phagocytosis, these Ca2+ signals were only modestly affected by pertussis toxin. Thus, the present data clearly indicate that the CD11b/CD18 integrin on human neutrophils is capable of inducing a prompt cytosolic-free Ca2+ signal. These findings directly support the recent suggestion that the CD11b/CD18 integrin is responsible for the "spontaneous oscillations" of cytosolic-free Ca2+ observed in adherent neutrophils and, at least partially, also explain how integrin-mediated adherence can modify the functional responsiveness of neutrophils to a subsequent agonist stimulation.

Antigens, CD↗

Structural and functional analysis of the human IgG-Fab receptor activity of streptococcal protein G.

Streptococcal protein G (SPG) shows specific binding activity to IgGs and serum albumins from various species. In order to investigate the structural domains of SPG responsible for the specific interaction with human IgG-Fab, the binding characteristics of a collection of recombinant receptors were analysed. The study includes receptors comprising different parts of the SPG molecule as well as chimeric receptors containing IgG-binding domains of staphylococcal protein A (SPA) fused to the N-terminal AB-region of SPG, which has been claimed to interact with human IgG-Fab. Purified defined gene products were allowed to compete for the binding to human IgG, human IgG-F(ab')2 fragments and human serum albumin (HSA) in several sets of competitive binding experiments. The results demonstrate that the C-terminal C domains have both IgG-Fc- and IgG-Fab-binding capacities, whereas the N-terminal AB region is responsible for the HSA-binding only. These results, which are in conflict with previous work, demonstrate that the binding to both the IgG-Fc and the IgG-Fab region is mediated by the same structurally distinct receptor region of SPG.

Bacterial Proteins↗

Immunological studies in giant cell arteritis.

The results of investigations on the humoral immunological mechanisms are conflicting in giant cell arteritis (GCA) and have not been able to explain the pathological findings in the inflamed arterial wall. Altogether, immunological studies suggest that a cell-mediated immune reaction, possibly against an autologous antigen, occurs locally in the arteritic lesions of GCA. The excellent effect of treatment with glucocorticosteroids on the inflammation in GCA can also be explained by this model. The glucocorticosteroids inhibit the synthesis of interleukin-1 (IL-1) by the macrophages and suppress the IL-2 production from the T cells (Palacios, 1982). The observed HLA-DR expression in the arterial wall can be accounted for by the sum of macrophages and activated T cells, the macrophages being the most probable antigen-presenting cells. The interdigitating reticulum cells observed in some of the GCA patients may also be involved in antigen presentation. What the antigen(s) may be is, however, still unknown, as are the factors initiating the inflammatory process. It has recently been possible to extract T lymphocytes from the inflamed tissue and to culture these cells in vitro. After culture, it is possible to study the gene for the T-cell receptor, and probably even the antigenic specificity of the T cells. I hope that this approach may lead to a better understanding of the pathogenic mechanisms in GCA.

Antibody Formation↗

T-cadinol: a pharmacologically active constituent of scented myrrh: introductory pharmacological characterization and high field 1H- and 13C-NMR data.

Fractionation of an ethyl acetate extract of scented myrrh (resin of Commiphora guidottii Chiov., Burseraceae), using the guinea pig ileum test to monitor pharmacological activity, resulted in isolation of the sesquiterpene (+)-T-cadinol. High field NMR spectroscopy yielded new detailed 1H- and 13C-NMR data for the compound. T-cadinol was shown to have a concentration-dependent smooth muscle relaxing effect on the isolated guinea pig ileum and a dose-dependent inhibitory effect on cholera toxin-induced intestinal hypersecretion in mice.

Animals↗

Formation of a glutathione conjugate and a semistable transportable glucuronide conjugate of N2-oxidized species of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rat liver.

We have previously shown that 2-hydroxamino-1-methyl-6-phenylimidazo[4,5-b]pyridine(2-h ydroxamino-PhIP) is the principal metabolite leading to mutations in Salmonella typhimurium TA98 and DNA damage in mammalian cells. In rat hepatocytes this metabolite can be further conjugated to 2-(N-beta-D-glucuronopyranosyl (hydroxamino)-1-methyl-6-phenylimidazo[4, 5-b]pyridine[N(OH)-gluc-PhIP]. Its rate of formation was increased in hepatocytes from polychlorinated biphenyl (PCB)-pretreated animals. This metabolite is the main metabolite of PhIP in bile and it is hydrolyzed both by human and rat intestinal bacteria. Smaller amounts are excreted into urine. The evidence for the proposed structure is based on 1H- and 13C-NMR, beta-glucuronidase-lability giving 2-hydroxamino-PhIP upon hydrolysis and on the results obtained by using biochemical enzyme inhibitors. N(OH)-gluc-PhIP may be important for genotoxic lesions and tumors of 2-amino-1methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in extrahepatic tissue. In hepatocytes and bile from PCB-pretreated rats a PhIP-glutathione conjugate, 2-glutathionyl-1-methyl-6-phenylimidazo[4,5-b]pyridine (GSH-PhIP) was also found. The evidence for the proposed structure is based on 1H-NMR and high-resolution mass spectrometry. The metabolite can also be produced by a direct nucleophilic substitution of the nitro group in 2-nitro-PhIP by glutathione (GSH) in vitro. The metabolite did not form from 2-hydroxamino-PhIP and GSH either directly or in the presence of glutathione S-transferase. The formation of GSH-PhIP in rat liver and isolated cells only at a high rate of 2-hydroxamino-PhIP formation (PCB-treated animals) indicates that 2-nitro-PhIP may be formed in the liver during such N-oxidation of PhIP.

Animals↗

Giant cell and Takayasu's arteritis.

Giant cell arteritis is a generalized vasculitis mainly affecting elderly people. The incidence is increasing, but only for women. The etiology is still unknown, but evidence suggests a cellular immunologic reaction against a local antigen present in the arterial wall. The disease can present itself with a great variety of symptoms. Constitutional symptoms such as fever, weight loss, and anorexia seem to be more common than hitherto believed. Onset of large artery involvement is independent of the evolution of the classic clinical symptoms. Peripheral synovitis is rarely seen in patients with polymyalgia rheumatica, and when it occurs, it is transient, nonerosive, and nondeforming. Glucocorticosteroids are the only generally accepted treatment in giant cell arteritis. After a higher initial dose of corticosteroids, most patients can be treated with a low maintenance dose, with little risk of steroid-induced osteoporosis. The erythrocyte sedimentation rate is still the best test for monitoring the disease.

Giant Cell Arteritis↗

Improvement of the effects of intrasplenic transplantation of hepatocytes after 90% hepatectomy in the rat by cotransplantation with pancreatic islets.

Acute liver failure is associated with high mortality. Whether support with transplanted hepatocytes improves the outcome is not established. We studied the potential beneficial effects of intrasplenic transplantation of hepatocytes in conjunction with islets of Langerhans on 90% hepatectomy-induced acute liver failure in rats. We found that all control rats died within 48 hr following 90% hepatectomy. In contrast, the mortality decreased significantly in rats transplanted with 10(7) hepatocytes into the spleen parenchyma at 1-3 days prior to 90% subtotal hepatectomy, whereas no significant reduction in mortality was seen in rats transplanted with hepatocytes immediately after the operation. However, cotransplantation of hepatocytes and 400 isolated pancreatic islets into the spleen reduced mortality when performed immediately after the 90% hepatectomy. Therefore, hepatocyte transplantation reduces mortality after 90% hepatectomy only if performed prior to the hepatectomy. However, transplantation of hepatocytes in conjunction with pancreatic islets reduces mortality when performed at the same time as 90% hepatectomy. Hence, the combined transplantation of hepatocytes and islets might offer support after liver failure.

Alkaline Phosphatase↗

A monoclonal IgM antibody to a methylcholanthrene-induced tumour. I. Specificity for alpha-N-acetylgalactosamine but with no cross-reactivity to the human blood group A determinant.

A monoclonal IgM antibody, H17, has been obtained from rats immunized with mouse fibrosarcoma cells from an in vitro established methylcholanthrene (MCA)-induced tumour. H17 shows specific and very selective binding to alpha-N-acetylgalactosamine (GalNAc alpha) when tested for reactivity to a panel of glycolipids. It cross-reacts with GalNAc alpha on the Forssman antigen extracted from dog small intestine, but not from the human blood group A determinant, a finding not commonly observed among antibodies with this specificity. Despite its specificity, H17 does not react with TA3-Ha, a mouse mammary adenocarcinoma, known to express the Tn antigen (GalNAc alpha-O-Ser/Thr). The uniqueness of H17 probably relates to the fact that it has been generated against an MCA-induced tumour rather than against the pure saccharide itself. Minimum energy conformation structures of different GalNAc alpha containing saccharide molecules were computer modelled to allow a plausible interpretation of the accessible site of GalNAc alpha for successful interaction with the H17 paratope as compared to other GalNAc alpha binding antibodies.

ABO Blood-Group System↗

Fibrin(ogen) degradation product peptide 6A increases femoral artery blood flow in dogs.

To determine the effects of peptide 6A (a fibrinogen-degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50 mumoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 mumoles min-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 +/- 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1 alpha in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI2 release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.

6-Ketoprostaglandin F1 alpha↗

von Willebrand factor antigen and plasminogen activator inhibitor in giant cell arteritis.

Sixty three patients (51 women, 12 men) with giant cell arteritis were studied by serial analyses of von Willebrand factor antigen (vWF: Ag) concentration and plasminogen activator inhibitor activity. Their mean age at the time of diagnosis was 71 years. Two hundred and one randomly selected subjects from the general population, aged 75 years, served as controls. The mean concentration of vWF:Ag in the patients with giant cell arteritis before the start of corticosteroid treatment was 2.63 (SD 1.35) IU/ml compared with 1.71 (0.69) IU/ml in the general population. The vWF:Ag concentration slowly decreased and reached the control range about 18 months after the diagnosis. The vWF:Ag did not correlate with the clinical group of giant cell arteritis nor with the results of temporal artery biopsy. Flare ups and vascular complications were not indicated by the vWF:Ag. Plasminogen activator inhibitor activity in the patients was not significantly different from that of the general population at any time. It was concluded that the determination of vWF:Ag and plasminogen activator inhibitor activity is of limited clinical value in the diagnosis, prognosis, and monitoring of steroid treatment in patients with giant cell arteritis.

Aged↗

Bile increases lipopolysaccharide release in experimental E. coli peritonitis.

Previous studies in rats showed increased mortality when bile was added to intraperitoneally injected Escherichia coli. In the present study bacterial counts and levels of lipo-polysaccharide (LPS) were determined in the peritoneal cavity and in blood 0.5, 1, 4 and 10 hours after induction of peritonitis with E. coli alone or together with bile. LPS was measured with gas chromatographic analysis of beta-hydroxymyristic acid, a characteristic component of E. coli-LPS. Bacterial counts and LPS levels in peritoneal fluid and blood rose higher in E. coli + bile peritonitis than in E. coli peritonitis. The intergroup difference in LPS levels was evident at 0.5 and 1 hour, whereas the bacterial counts began to differ at 2 hours. Presence of intraperitoneal bile in E. coli peritonitis thus produced rapid rise in LPS levels that could not be caused by bacterial numbers alone. This early load of LPS may help to explain the noxious effect of bile in E. coli peritonitis.

Animals↗

Tumor seeding occurring after fine-needle biopsy of abdominal malignancies.

Percutaneous fine-needle aspiration biopsy is a commonly used diagnostic procedure with a high accuracy and a low complication rate. However, tumor seeding in the biopsy tracts has been recorded with a frequency of one in 20,000-40,000 biopsies. We report 5 cases of percutaneous tumor seeding recorded after 5,000 fine-needle biopsies of abdominal malignancies at our institution. The risk of implantation metastases induced by fine-needle biopsy warrants consideration in patients with abdominal malignancies since it may compromise the outcome of radical surgery. It should only be performed when the result of the procedure has a direct impact on the choice of therapy.

Abdominal Neoplasms↗

Effect of bile on liver function tests in experimental E. coli peritonitis in the rat.

Hepatic dysfunction is a frequent finding in sepsis and peritonitis. In the present study, hepatic function in experimental peritonitis in the rat was determined by measuring serum levels of bilirubin, alkaline phosphatase (ALP), glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), together with antipyrine (AP) clearance as a determinant of microsomal function. Peritonitis was induced by intraperitoneal injection of 3 x 10(8) colony-forming units of E. coli together with either 1.0 ml bile or saline. E. coli + bile peritonitis rats had significantly elevated levels of bilirubin, ALP, GOT and GPT as compared with both controls and rats with peritonitis induced by E. coli alone. The derangements gradually increased with time over the 10-hour period studied. In contrast, no reduction of AP clearance was observed in the peritonitis models. On the contrary, AP clearance was enhanced at 10 hours after induction of peritonitis by E. coli alone. In conclusion, hepatic dysfunction as revealed by routine laboratory tests is seen early in experimental peritonitis in the rat, but this is not accompanied by a reduced AP clearance rate.

Animals↗

Abdominal sepsis following liver resection in the rat.

A standardized 2/3 liver resection was performed in the rat. One and seven days following liver resection, gram-negative sepsis was induced by cecal ligation and puncture (CLP). Mortality significantly increased following CLP one day after hepatectomy, but no difference was to be seen after seven days as compared with sham operated animals. Clearance of radiolabeled heat-killed 125I E. coli injected intravenously was significantly decreased one day following liver resection, but not after seven days. The capability of bacterial clearance and survival correlated well with the increase in weight of the liver remnant following liver resection, as did organ uptake of radiolabeled bacteria within the liver, spleen and lungs, as a measure of reticuloendothelial system function. Splenic and pulmonary uptake initially increased following liver resection, but normalized within seven days. In conclusion, the present study shows that the liver is responsible for most of the reticuloendothelial system function and that a major liver resection increases the risk of fatal outcome before regeneration of the liver remnant has occurred, despite normal function of the residual liver tissue.

Animals↗

Conservative surgery for vulvovaginal melanoma.

22 cases of vulvovaginal melanoma seen in Umeă between 1963 and 1989 were retrospectively reviewed. According to FIGO, 11 were in Stage I, 6 in Stage II, 3 in Stage IV and 2 in Stage VI. Most patients received only conservative surgery and/or radiotherapy. 8 patients (36%) were alive at 5 years and 4 survived more than 10 years. The longest survivor at 17 years is still alive without evidence of disease. Conservative surgery seems to give as good results as radical operation for vulvovaginal melanomas and FIGO clinical staging appears to be of limited prognostic value.

Adult↗