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Biomedical subjects

R Andersson

Publications and source records attributed to R Andersson.

At least 19 recordsLinked to original sources

Bacterial translocation after major hepatectomy in patients and rats.

Bacterial infections are frequent complications after liver resection. Of 138 patients who underwent major hepatectomy, 11 patients (8%) developed intra-abdominal sepsis in the postoperative period. Seven bacterial strains of gut origin were isolated from the abdominal cavity. Eight patients had multiple bacteria cultured. In the experimental studies on rat models, positive mesenteric lymph node cultures were seen 2 hours after removal of 70% and 90% of the total weight of the rat liver, and 12 hours after 50% hepatectomy, persisting for 3 and 4 days after 50% and 70% hepatectomy, respectively. The incidences of bacteremia 2 and 4 hours after 90% hepatectomy were 80% and 100%, respectively; 6 hours after 70% liver resection, the incidence of bacteremia was 33%. Blood cultures were positive in only 6% of the rats following 50% hepatectomy, and in none of the controls. Thus, bacterial translocation occurs in the early course after hepatectomy, the incidence being proportional to the amount of liver tissue removed.

Abdomen

Effect of biliary decompression on reticuloendothelial function in jaundiced rats.

The recovery of reticuloendothelial system (RES) function following decompression of obstructive jaundice was studied using a rat model with bile duct ligation and side-to-side choledochoduodenostomy. Histopathological changes in the liver were still present 5 weeks after relief of jaundice, while results of liver function tests had returned to normal. RES function evaluated by the blood clearance and organ uptake of radiolabelled Escherichia coli using a corrected phagocytic index gradually returned to normal following biliary decompression. The severely impaired RES activity noted 1 week after operation may explain the increased incidence of sepsis and renal insufficiency in the early period after biliary surgery in jaundiced patients.

Animals

Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

Rats were fed with freeze-dried oatmeal soup fermented by six different Lactobacillus strains from rat and man; the formula is intended for enteral feeding. The serum cholesterol levels after 10 d were lower for rats eating oatmeal as compared to a commercial product, Biosorb Sond. Colonizing ability of the administered strains were evaluated in vivo. Only Lactobacillus reuteri R21c were able to, effectively, colonizing the mucosa; it represented about 30% of the Lactobacillus population 24 d after termination of the administration. L. reuteri R21c was easily recognized by the ability to produce a yellow pigment on agar plates. The identity was confirmed by carbohydrate fermentations (API 50CH), plasmid pattern and endonuclease restriction analysis of the chromosomal DNA.

Animals

Systematics of the Lactobacillus population on rat intestinal mucosa with special reference to Lactobacillus reuteri.

The systematics of the Lactobacillus population of the intestines of 88 different rats was studied; 80 rats had been fed on fermented oat-meal soup (Molin et al. 1992). One-hundred-twenty-two Lactobacillus strains from the intestinal mucosa were phenotypically classified together with twenty-eight reference strains of Lactobacillus and Leuconostoc, using 49 unit characters. Data were examined using Jaccard coefficient, and unweighted pair group algorithm with arithmetic averages. Two major and eleven minor clusters were defined at the 76% SJ-similarity level: Cluster 1 included thirty isolates which could not be identified further, but had resemblance to the type strains of L. jensenii, L. gasseri, L. crispatus, and to some extent to L. acidophilus. Cluster 12 including fifty-four intestinal isolates was identified as L. reuteri; and so was cluster 13 (five isolates). Isolates of the major clusters were found in all parts of the intestines. The genomic homogeneity of the L. reuteri isolates was scrutinized by endonuclease restriction analysis of the chromosomal DNA, and the isolates could be divided into six genomic strains.

Algorithms

Reaction of the N2-acetoxy derivative of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) with 2'-deoxyguanosine and DNA. Synthesis and identification of N2-(2'-deoxyguanosin-8-yl)-PhIP.

The direct acting mutagenic N2-hydroxylated metabolite of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) does not react with DNA. Upon acetylation of the N2-hydroxy-PhIP with acetic anhydride two products could be detected. Mass spectrometric analysis showed that both products were monoacetyl derivatives of N2-hydroxy-PhIP. One of the products did not show any reactivity towards DNA and is probably the N-acetyl derivative of N2-hydroxy-PhIP. The other product which is most likely to be N2-acetoxy-PhIP reacted with DNA and 2'-deoxyguanosine but not with 2'-deoxycytidine, 2'-deoxyadenosine or 2'-deoxythymidine. The PhIP-2'-deoxyguanosine adduct was purified and characterized by mass spectral, 1H and [13C]NMR analysis, showing that PhIP like the other cooked food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline, had reacted with C-8 of guanine forming N2-(2'-deoxyguanosin-8-yl)-PhIP. HPLC analysis of enzymatically hydrolyzed calf thymus DNA which had been reacted with N2-acetoxy-PhIP showed one adduct which was chromatographically and spectroscopically identical to N2-(2'-deoxyguanosin-8-yl)-PhIP. HPLC separation followed by liquid scintillation counting of hydrolyzed liver DNA from a rat dosed with [3H]PhIP showed that radioactivity coeluted with the hydrolysis product of the synthetic PhIP-2-deoxyguanosine adduct, indicating that PhIP in vivo also forms an N2-(2'-deoxyguanosin-8-yl)-PhIP adduct.

Animals

Analysis of J beta gene segment usage by CD4+ and CD8+ human peripheral blood T lymphocytes.

Certain T cell antigen receptor V gene products in man have been shown by us and others to display a reproducible bias for preferential expression in CD4+ or CD8+ T cell subsets. In order to investigate whether such a skewed representation of V gene segments is also present at the J gene segment level, we tested the relative J beta gene usage by V beta 5.1 + T cells, as this V beta gene is biased towards CD4+ T cell expression in virtually all individuals. To analyze the usage of the 13 J beta gene segments, we developed a new approach using V beta 5.1 and C beta specific oligonucleotides as 5' and 3' primers respectively for polymerase chain reaction (PCR) amplification of cDNA derived from CD4+ or CD8+ peripheral blood lymphocyte (PBL) T cells. The PCR products were visualized for reactivity with individual J beta 1.1-1.6 and J beta 2.1-2.7 32P-labelled oligonucleotide probes using autoradiography and quantitative gel-scanning. Eleven normal blood donors provided the PBL T cells. The results showed that in every individual's V beta 5.1+ T cell populations (CD4 and CD8), all V beta/J beta combinations were used although at varying but reproducible levels for each J beta gene. Thus, no discernible disallowance of combinations existed. Moreover, we could show that six of 13 J beta genes were unequally expressed when compared in pairs with regard to expression in CD4+ and CD8+ T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence

A persistent T cell expansion in the peripheral blood of a normal adult male: a new clinical entity?

A dramatic and persistent T cell expansion in a healthy adult male was initially identified, using anti-T cell receptor for antigen (TCR)-specific MoAbs. The expanded T cells were found to be expressing TCR containing V alpha 12.1 and V beta 5.2, and they composed approximately one third of all the CD8+ T cells. The cells were shown to be not only non-activated (HLA-DR-, IL-2R-) but also of 'virgin' cell type (CD45RA+/CD45RO-) and they persisted over the observation period of more than one and a half years. Various T and B cell markers, and all other laboratory and physical parameters analysed, were normal. The expanded CD8+ T cells were further characterized by polymerase chain reaction (PCR) amplification, using V beta- and C beta-specific primers, followed by hybridization with J beta-specific probes. Close to 90% of the V alpha 12.1+ V beta 5.2+ T cells were found to utilize the J beta 2.5 gene segment, thus strongly suggesting the expanded T cells to be monoclonal. The condition may constitute a T cell counterpart to 'monoclonal gammopathy of undetermined significance' (MGUS), and by analogy we suggest it should be designated 'monoclonal T cell expansion of undetermined significance' (MTUS).

Adult

Medical vocational guidance for adolescents--is it effective?

The outcome of school medical vocational guidance was studied in all 1595 students enrolled in 1987 in grade 9 in the primary schools of Linköping. In grade 9, the school health service had listed 249 students with a chronic disorder. These were sent a questionnaire which was answered by 235 students. Only 5/235 stated that vocational information from physicians and school nurses had been important for their choice of career. No more than 22/235 had chosen a medically ill-suited secondary school study course. This figure is close to the number expected, assuming that all choices of study courses are at random. At follow-up in May 1989, no one said that they had changed study course or work due to their medical disorder. Thus, school medical vocational guidance seems to have little effect on the vocational choices of adolescents with chronic disorders.

Adolescent

Pharmacokinetics of mitomycin C following hepatic arterial chemoembolization with gelfoam.

Twelve mongrel dogs were randomly allocated into two groups using matched paired-design. Catheters were inserted into the hepatic artery, hepatic vein and the femoral vein, respectively. In the first group, gelfoam supplemented with mitomycin C (MMC) was injected into the hepatic artery, whereas the second group received a hepatic arterial injection of MMC solution alone. Simultaneous blood sampling from the hepatic and femoral vein at regular intervals was performed. MMC concentrations in plasma was determined using high performance liquid chromatography (HPLC) and the pharmacokinetics of MMC were determined. MMC concentrations in hepatic and femoral veins did not differ and no significant difference in pharmacokinetics was found when comparing MMC administration into the hepatic artery with or without gelfoam supplementation. Thus, our results revealed that gelfoam could not delay the clearance of MMC from the liver.

Animals

Increased passage of bovine serum albumin over the respiratory tract after intratracheal instillation during septic shock in rats.

Sepsis may initiate acute respiratory distress syndrome which may be accompanied by an increased pulmonary epithelial-endothelial permeability. In this study, sepsis was induced by an intraperitoneal implantation of gelatine capsules containing Escherichia coli/Bacteroides fragilis/adjuvant substance. The importance of bacteria in sepsis-related lung injury was studied in rats given an intraperitoneal injection of E. coli or in rats given the adjuvant substance alone in capsules intraperitoneally. Rats with empty capsules were used as controls. The rats were intratracheally instilled with bovine serum albumin (BSA) directly after the capsule implantation or the injection of E. coli, and the passage over the lower respiratory tract was assessed as blood plasma levels of immunoreactive BSA. The plasma BSA levels in the control rats increased continuously up to 24 h after intratracheal instillation. This increase was significantly augmented already 1 h after the septic challenge, i.e. before any clinical symptoms were observed, in both the septic rats and the rats with the E. coli injected intraperitoneally. Furthermore, the time required to obtain maximal plasma BSA levels was shorter in septic, adjuvant-exposed and in E. coli-injected rats than in the controls. The plasma levels and the total BSA passage over the lower respiratory tract was significantly higher (p less than 0.001) in the septic and in the E. coli-injected rats than in the adjuvant-exposed and the control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis.

There exists no ideal model for experimental ulcerative colitis in common laboratory animals. Therefore, we tried in the present study to establish a reproducible model for inducing colitis in rats by using acetic acid. A blind loop of the colon including the cecum, ascending colon and part of the transverse colon, was brought out through two colostomies. After mechanical washing with warm normal saline, acetic acid was instilled at different doses (4, 6 and 8%) for different exposure times (10, 15, 20, 25 and 30 s). The excluded colon was examined by light microscopy on the 1st, 2nd, 3rd, 4th, 7th and 14th days after operation and acetic acid instillation. We found that 4% acetic acid for 15 s produced a moderate, superficial colitis on the 1st day after operation, whereafter a uniform colitis evolved in all rats on the 4th day after operation. The developed colitis showed morphological similarities with human ulcerative colitis. Signs of healing and regeneration of the mucosa were seen on the 7th day, and the mucosa became almost normal at the 14th day after operation. 6 or 8% acetic acid solution or exposure times exceeding 15 s resulted in severe, deep colitis with a concomitant high mortality rate. In contrast, at exposure times less than 15 s, acetic acid induced only mild superficial colitis. We conclude that by using 4% acetic acid for 15 s in the excluded colon a uniform and reproducible colitis pathologically resembling human ulcerative colitis could be achieved. Furthermore, no mortality was encountered and the general health of the rats was similar to that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates

Effects of phosphatidylcholine and phosphatidylinositol on acetic-acid-induced colitis in the rat.

The therapeutic effects of exogenous phosphatidylcholine and phosphatidylinositol on acetic acid-induced colitis in rats were evaluated. A uniform colitis developed 4 days after instillation of 4% acetic acid for 15 s in an excluded colonic segment, also resulting in a 6-fold increase in mucosal permeability. Instillation of 12.5 mg phosphatidylcholine once daily from the day after acetic acid instillation and for the following 2 days prevented partially the development of colitis causing partial mucosal restoration. By increasing the phosphatidylcholine dose to 25 and 50 mg, a better preventive effect was achieved. By starting the phosphatidylcholine instillation immediately after the acetic acid exposure, almost complete prevention of the colitis could be obtained. Similarly, 50 mg phosphatidylinositol in each instillation with the first administration immediately after acetic acid administration resulted in complete prevention of the colitis and a significant decrease in mucosal permeability expressed as a plasma exudation into the colonic lumen. Similar results were obtained when phosphatidylcholine was administered immediately after acetic acid, but the drug then had to be applied twice daily. In contrast, a single application of the same total dose (150 mg) of the two different phospholipids, either 30 min before or immediately after acetic acid administration, could not prevent the development of colitis. It is concluded that both phosphatidylcholine and phosphatidylinositol have a therapeutic effect on the development of acetic acid-induced colitis in the rat.

Acetates

Cytomegalovirus infections and toxoplasmosis in heart transplant recipients in Sweden.

The morbidity of cytomegalovirus (CMV) infection and toxoplasmosis was evaluated in 75 heart transplant recipients. Among the 73 patients who survived more than one week after transplantation, 16 (22%) acquired primary CMV infection and 30 (41%) had evidence of secondary infection. All CMV seronegative recipients receiving hearts from seropositive donors developed CMV infection. The majority of infections (42/46) occurred during the first 4 months after transplantation. Overall, the incidence of symptomatic CMV disease was 44%. The infections were generally mild and only 1 death was attributed to primary CMV disease complicated by bacterial septicaemia and multiple organ failure. The severity of CMV disease was greatest among those with primary infection. There were 3 cases of toxoplasmosis. Two patients were toxoplasma seronegative before transplantation and developed clinical and serological signs of infection 2-3 months after transplantation despite receiving organs from seronegative donors. Of toxoplasma seronegative recipients receiving allografts from seropositive donors 3/4 were prophylactically treated with pyrimethamine for 6 weeks. None developed clinical or serological signs of toxoplasmosis while one patient who received trimethoprim-sulfamethoxazole had a subclinical infection.

Adolescent

Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP.

The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.

Calcitonin Gene-Related Peptide

The influence of biliary obstruction and sepsis on reticuloendothelial function in rats.

Obstructive jaundice is frequently associated with septic complications and renal impairment. The present study was performed in order to evaluate reticuloendothelial system (RES) function in obstructive jaundice and the influence of a septic challenge. Male Sprague-Dawley rats were allocated into four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of the common bile duct (CBD) alone and CBD+CLP, respectively). Mortality, blood clearance and organ distribution of 125I labelled Escherichia coli were determined. Mortality in sepsis (CLP) significantly increased in jaundiced animals (p less than 0.033). Blood clearance of radiolabelled E. coli was significantly impaired in both jaundiced groups. In jaundiced animals, hepatic localisation and renal uptake of E. coli significantly increased (p less than 0.001), while radioactive counts in bile significantly decreased (p less than 0.01). Changes in organ distribution of bacteria did not depend on alterations in blood flow. Thus, RES function was impaired in jaundiced animals and mortality increased in a concomitant septic challenge in jaundiced animals.

Animals

Intraperitoneal 5-fluorouracil in the management of colorectal liver cancer.

Twenty-five patients with colorectal liver metastases had a subcutaneous portal connection with a peritoneal catheter implanted for the intraperitoneal (i.p.) administration of 5-fluorouracil (5-FU). In five patients, the malignant disease rapidly progressed and the implanted catheter system was never used. Among the remaining 20 patients, seven patients had i.p. 5-FU as adjuvant treatment following liver resection and 13 patients received palliative chemotherapy (5-FU) owing to unresectable liver metastases. 5-FU was administered on a regular basis every 4 to 6 weeks by continuous infusion of 1000 mg/day (approximately 15 mg/kg/day) for 5 days. In seven patients, i.p. chemotherapy was managed on an outpatient basis. In general, i.p. 5-FU treatment was well tolerated with only minor abdominal complaints during the initial treatments. No definite effect on survival has been noted. All patients (n = 13) receiving palliative i.p. 5-FU died after a median of 4 (range 1.5-18) months. Two patients receiving adjuvant chemotherapy died owing to recurrence after 20 and 23 months, while five patients are alive, two with recurrent disease and three without, after 14-35 months.

Adult