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Biomedical subjects

E Nilsson

Publications and source records attributed to E Nilsson.

At least 73 records · Page 4Linked to original sources
PubMed1996

A short diagnostic delay is more important for rectal cancer than for colonic cancer.

OBJECTIVE: To study the association between a short diagnostic delay and tumour stage in patients with colonic and rectal cancer. DESIGN: Prospective study. SETTING: Multicentre study, Sweden. PATIENTS: 336 patients with colonic, and 218 patients with rectal cancer. MAIN OUTCOME MEASURES: Incidence and duration of symptoms, delay in diagnosis, and stage at diagnosis. RESULTS: Patients with rectal cancer and a delay of less than a month between start of symptoms and diagnosis included a significantly larger proportion of Dukes' A tumours than patients with a longer delay (p = 0.004). Delay in patients with colonic cancer did not correlate with stage. CONCLUSION: A short delay in the diagnosis of rectal cancer was associated with better staging. This could not be shown for colonic cancer, which may be attributable to its initially vague symptoms and to a subgroup of highly malignant tumours with rapidly progressive symptoms.

Adult↗
PubMed1995

Carboxyl-terminal prodomain-deleted human leukocyte elastase and cathepsin G are efficiently targeted to granules and enzymatically activated in the rat basophilic/mast cell line RBL.

The hematopoietic neutral serine proteases leukocyte elastase and cathepsin G are synthesized as inactive precursors, but become activated by removal of an amino-terminal dipeptide and are stored in granules. Moreover, the pro forms of elastase and cathepsin G show carboxyl-terminal prodomains of 20 and 11 amino acids, respectively, which are not present in the mature enzymes. To investigate mechanisms of processing, activation, and granular targeting, we have utilized transgenic expression of myeloid serine proteases in the rat basophilic/mast cell line RBL-1 (Gullberg, U., Lindmark, A., Nilsson, E., Persson, A.-M., and Olsson, I. (1994) J. Biol. Chem. 269, 25219-25225). Leukocyte elastase was stably expressed in RBL-1 cells, and the translation products were characterized by biosynthetic labeling followed by immunoprecipitation, SDS-polyacrylamide gel electrophoresis, and fluorography. Processing of a main pro form of 34 kDa into mature 31- and 29-kDa forms was demonstrated. Translocation of mature forms to granule-containing fractions was shown by subcellular fractionation experiments. The processed forms were enzymatically active, judging by the occurrence of amino-terminal processing demonstrated by radiosequence analysis, the acquisition of affinity for the protease inhibitor aprotinin, and the appearance of elastase activity in transfected RBL cells. To investigate the function of the carboxyl-terminal prodomains, deletion mutants of leukocyte elastase and cathepsin G lacking the carboxyl-terminal extension were constructed and transfected into RBL cells. Our results show that as full-length proteins, the deletion mutants were converted to active enzymes and transferred to granules with kinetics similar to that of wild-type enzymes. We conclude that human leukocyte elastase and cathepsin G are converted into enzymatically active forms when expressed in RBL cells and targeted for storage in granules; the carboxyl-terminal prodomains are necessary neither for enzymatic activation nor for targeting to granules in RBL cells.

Amino Acid Sequence↗
PubMed1995

Photodynamic therapy for recurrent nasopharyngeal cancer.

OBJECTIVE: A pilot study to determine if photodynamic therapy could be a safe and efficacious treatment for recurrent or persistent nasopharyngeal cancer. DESIGN: A consecutive sample intervention study with comparison with historic control subjects. SETTING: Tertiary referral hospital. PATIENTS: All patients with recurrent or persistent nasopharyngeal cancer following radiation therapy were considered for treatment. Patients with tumors with a depth of more than 10-mm invasion on computed tomographic scans were excluded, as were patients with recurrent metastasis to the neck. Five patients were thus acquired during a 3-year period. INTERVENTION: Four patients were injected intravenously with hematoporphyrin derivative (2.5 mg/kg) and one patient with porfimer sodium (2 mg/kg) (Photofrin, Quadra Logic Technologies, Vancouver, British Columbia) 48 hours before treatment. The drug was activated by a 630-nm laser light passed down a 1-mm core quartz fiber to a miniaturized convex mirror positioned in the nasopharynx via the contralateral nasal cavity. This procedure was carried out under topical anesthesia. MAIN OUTCOME MEASURE: Survival was determined after a minimum follow-up of 4 years. RESULTS: To date, three of five patients treated have no evidence of disease, with follow-up times of 51, 52, and 60 months, respectively. The patient with the longest survival time had been unsuccessfully treated with 136 Gy of ionizing radiation preceding photodynamic therapy. CONCLUSIONS: Long-term tumor control can be achieved by photodynamic therapy in cases where very high doses of ionizing radiation have failed. The entire treatment can be accomplished in 30 minutes under topical anesthesia. The technique carries no serious side effects.

Adenocarcinoma↗
PubMed1995

Outcome of surgery for colorectal cancer in a defined population in Sweden from 1984 to 1986.

PURPOSE: This study was designed to investigate incidence, treatment, and outcome for patients with colorectal cancer. METHODS: From 1984 to 1986 in Ostergötland, a county in Sweden with a defined population, a prospective registration using a computerized protocol was undertaken. RESULTS: In the surgical departments 596 cases were diagnosed and 31 more cases were diagnosed in other departments, bringing the incidence to 53 cases per 100,000 inhabitants per year. Of the cases, 14 percent presented as emergencies. The resectability rate was 90 percent, and the rate of curative operations was 74 percent. Postoperative mortality within 30 days was 2.9 percent. Crude five-year survival for all patients was 40 percent, and the corrected survival rate was 53 percent. After curative resection the crude five-year survival rate was 53 percent, and the corrected survival rate was 70 percent. Prognosis was better for colon than for rectal cancer, 76 percent vs. 59 percent corrected five-year survival rate. For rectal cancer the local recurrence rate was 20 percent after curative resection. CONCLUSIONS: The prognosis was improved compared with a previous study from the same area because of decreased postoperative mortality, increased rate of operations for cure, and an increased five-year corrected survival rate. Local recurrence after rectal cancer was still high but may be reduced with improved surgical technique.

Aged↗
PubMed1995

Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid.

BACKGROUND & AIMS: Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid. METHODS: Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration. RESULTS: A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%. CONCLUSIONS: The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.

Acids↗
PubMed1995

Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain.

Forty-five patients were allocated randomly to receive either a single intrathoracic block of four intercostal nerves, a continuous thoracic extradural infusion or a continuous paravertebral infusion of bupivacaine. Patients were allowed additional i.v. boluses of morphine via a PCA device. Segmental spread of pinprick analgesia was comparable in the groups for up to 20 h. Up to 2 h after the block, plasma concentrations of bupivacaine were greater in the intercostal group and there was large interindividual variation. There were no significant differences between the groups in pain, morphine consumption, respiratory function or adverse events. Moderate to severe respiratory depression was detected in 14 patients more than 2 h after operation.

Adult↗
PubMed1995

Rabbit polymorphonuclear granulocyte function during ethanol administration--migration and oxidative responses in a joint with immune complex synovitis.

Functional impairments of polymorphonuclear granulocytes (PMN) are believed to contribute to hampered inflammation and host defence in alcoholics. We studied effects of i.v. ethanol administration on PMN responses in rabbits during induction of a knee-joint synovitis. The synovitis conferred systemic effects, since chemiluminescent responses of peripheral blood PMN to opsonized zymosan and phorpbol myristate acetate (PMA) increased 6.4- and 17.9-fold, respectively. Chemiluminescent responses of synovial PMN were further amplified. This up-regulation was reduced to 33% in rabbits treated with ethanol when opsonized zymosan was used as the PMN stimulus; in contrast, PMA responses were unaffected. The appearance and migration of PMN to the synovitis joint were normal despite a blood ethanol concentration of 0.5%. Thus, ethanol impaired release of oxygen metabolites from PMN, but not the delivery of cells at an inflammatory site.

Animals↗
PubMed1995

Contact urticaria with anaphylactic reactions caused by occupational exposure to iridium salt.

This paper presents the case of a non-smoking and non-atopic male, exposed to iridium chloride at work, who developed respiratory tract symptoms and contact urticaria. Application of iridium salt to normal skin caused contact urticaria. An iridium chloride prick test showed a positive reaction and a scratch test produced anaphylactoid reactions. Platinum salt allergy was excluded through prick testing with hexachloroplatinate solution. There is no previous report describing a case where an individual has a positive prick test reaction to iridium salts and simultaneously a negative one to platinum salts. The results are interpreted as immediate-type hypersensitivity (Type I allergy?) to iridium salt. The route of sensitization was probably through the airways. Further testing showed that iridium salt allergy could persist for at least 18 months after exposure ceases. 14 employees at the same factory were prick tested with iridium and platinum salts with negative results. Prick testing is recommended as a method of first choice when investigating a person with suspected iridium salt allergy.

Adult↗
PubMed1995

An experimental study of gastric stump carcinoma in Wistar rats.

The risk of gastric stump carcinoma is increased 15-20 years after gastric resection for benign disease. Reflux of duodenal juice, bacterial overgrowth and formation of N-nitroso compounds are possible etiological factors. There is a geographical variation in the incidence of gastric cancer, possibly explained by differences in food intake. Experimentally it is possible to induce gastric stump carcinoma in rats without the addition of exogenous carcinogens. The aim of this study was: 1) to find the incidence of gastric carcinoma in rats subjected to BII resection and followed for 10 months, and 2) to examine if acetic acid, a common dietary factor, could influence the development of gastric carcinoma. Amongst BII-operated male Wistar rats, infiltrating carcinoma was found in 5/20 on a normal diet and in 5/24 exposed to acetic acid (NS). Benign mucosal changes were seen in 12/20 and 16/24 respectively (NS). With the exception of a profound inflammation in one sham-operated animal, no mucosal pathological changes were found in 24 sham-operated and 24 control animals where no operation was performed.

Acetates↗
PubMed1995

Lipofuscin accumulation and ageing of fibroblasts.

Lipofuscin accumulates in postmitotic cells. In human fibroblasts, accumulation of lipofuscin as measured by cellular autofluorescence is exponential at first, but stops at a certain level. At the same time, cell death starts to decrease cell numbers significantly. Artificial lipofuscin-like material can be prepared by UV-crosslinking of mitochondrial preparations. This material is easily phagocytosed by human fibroblasts and results in an increased cellular lipofuscin accumulation. Such a forced lipofuscin accumulation is sufficient to block cellular proliferation within a short time and to induce cell death as soon as the cellular lipofuscin autofluorescence reaches the same upper limit as that observed in senescent cells. It is concluded that accumulation of lipofuscin in postmitotic cells is not just an innocent consequence of ageing, but rather one amongst the important causes of senescence.

Aging↗
PubMed1995

Ethanol affects leukotriene generation and leukotriene-induced functional responses in human polymorphonuclear granulocytes.

Since ethanol has been shown to inhibit the inflammatory response, we evaluated whether ethanol affected generation of leukotrienes in polymorphonuclear granulocytes (PMN) in vitro. Using the calcium ionophore A23187 as stimulus, the leukotriene B4 (LTB4) and leukotriene C4 (LTC4) generation were dose-dependently impaired by ethanol. No significant difference in the levels of the omega-oxidized metabolites was observed. However, the total LTB4 production (LTB4 plus omega-oxidized metabolites) was significantly decreased in the samples treated with ethanol. Furthermore, ethanol also modulated LTB4-induced functional responses. PMN aggregation, oxidative metabolism and elastase release were all inhibited in the presence of 1% ethanol (to 74 +/- 15%, 50 +/- 4% and 57 +/- 3% of controls, respectively). However, ethanol had no effect on intracellular calcium mobilization or on the change of the PMN membrane potential induced by either LTB4 or A23187. Thus, a possible mechanism for the reduced functional PMN responses in the presence of ethanol might be impaired generation of leukotrienes, but it is conceivable that ethanol impairs also other steps of the stimulus response coupling since the LTB4-induced functional responses were inhibited.

Calcimycin↗
PubMed1995

Involvement of the tumor suppressor gene p53 in tumor necrosis factor-induced differentiation of the leukemic cell line K562.

The cDNA of the human wild-type p53 tumor suppressor gene was constitutively overexpressed in the leukemic cell line K562 (which lacks detectable amounts of p53 protein) in order to investigate the consequences for growth and differentiation. Several stable clones were established by transfection of the expression vector pc53SN3. Expression of p53 protein was characterized by biosynthetic labeling and immunoprecipitation with the monoclonal antibodies pAb 1801 (reacting with wild-type and mutant human p53), pAb 240 (reacting with mutant human p53) and pAb 1620 (reacting with wild-type human p53). All clones which were 1801+, 240-, 1620- or 1801+, 240-, 1620+ were defined as "wild-type-like p53-expressing" clones. Our results show that expression of p53 protein is compatible with continuous proliferation of K562 cells. The growth characteristics of wild-type-like p53-expressing clones did not differ from that of control clones. However, the former were more sensitive than p53-negative control clones to growth inhibition by tumor necrosis factor (TNF), a cytokine with a potential role in growth and differentiation of myeloid leukemic cells. In addition, a 2- to 4-fold increase of the amount of hemoglobin, a marker of erythroid differentiation, was observed when wild-type-like p53 protein-expressing clones were incubated with TNF. This suggests that differentiation is the mechanism responsible for the increased TNF sensitivity of these clones. Our results support a role for p53 in mediating growth inhibitory and differentiation inducing signals by TNF.

Antibodies, Monoclonal↗
PubMed1994

Processing of human cathepsin G after transfection to the rat basophilic/mast cell tumor line RBL.

The azurophil granules of neutrophil granulocytes contain neutral proteases such as leukocyte elastase and cathepsin G. These are synthesized as inactive precursors, but following proteolytic processing, they are stored in granules as active enzymes. We describe the establishment of a transgenic cellular model for expression of the human myeloid serine protease cathepsin G. The cDNA for preprocathepsin G was stably expressed in the rat basophilic/mast cell line RBL-1 and the translation product was characterized by use of biosynthetic labeling followed by immunoprecipitation, SDS-polyacrylamide gel electrophoresis, and fluorography. Conversion into complex form of an asparagine-linked carbohydrate unit of approximately 3.5 kDa was shown, as judged by the products obtained upon treatment with endoglycosidase H and N-glycanase. Proteolytic processing of 32.5-kDa procathepsin G into a 31-kDa form, within 1-2 h after synthesis, was demonstrated by pulse-chase experiments. Further processing into a 30-kDa form also occurred to a minor extent. The processed forms were enzymatically active, as judged by affinity for the serine protease inhibitors diisopropylfluorophosphate and aprotinin. Translocation of processed forms of cathepsin G to high density fractions, indicating targeting of the protease to granules, was demonstrated by subcellular fractionation. The weak base NH4Cl was shown to delay the processing and enzymatic activation of cathepsin G, whereas the monovalent ionophore monensin completely inhibited both events. Our data demonstrate that human cathepsin G transfected to rat RBL-1 cells, is proteolytically processed into enzymatically active forms and that subcellular transfer to granular organelles occurs. As the processing of transgenic human cathepsin G corresponds to that of endogenous protease of myeloid cells, the model should provide new unique possibilities to further characterize the activation and granular targeting of myeloid serine proteases.

Amidohydrolases↗
PubMed1994

High expression of V gamma 8 is a shared feature of human gamma delta T cells in the epithelium of the gut and in the inflamed synovial tissue.

We have analyzed the V-gene usage in gamma delta T cells of the human gut and joint by using a new mAb (B18) specific for V gamma 8 of human TCR-gamma delta+ T cells. The B18+ population constituted a minor subset of the gamma delta T cells in peripheral blood (PB) of healthy persons (6 +/- 5%) and only 1 of 35 gamma delta T cell clones analyzed was positive. In contrast, the B18+ subset was a dominant gamma delta T cell population among intraepithelial lymphocytes (IEL) derived from the human intestine (74 +/- 29, p < 0.002), and two of three IEL clones from patients with coeliac disease were B18+. Interestingly, a higher proportion of B18+ gamma delta T cells was found in the synovial fluid of patients with rheumatoid arthritis (RA) (21 +/- 18%, 0.02 < p < 0.05) compared with normal PB. Furthermore, the B18+ subset was more frequent among IL-2-expanded gamma delta T cells (42 +/- 20%) derived from synovial tissue than among IL-2-expanded cells derived from synovial fluid (p < 0.002) and PB from RA patients (p < 0.02) as well as normal PB (p < 0.002). The V-gene usage of 13 gamma delta T cell clones from the synovial fluid of arthritic patients was analyzed. All B18+ clones (n = 7) expressed mRNA for V gamma 8 together with mRNA for V delta 1 (n = 5) or mRNA for V delta 3 (n = 2). None of the B18- clones expressed V gamma 8 (n = 6). We conclude that the gamma delta T cell that expresses V gamma 8, together with mainly V delta 1, is a major gamma delta T cell subset among the IEL of the gut and a highly frequent subset in the synovial tissue of patients with RA. This subset may correspond to the mouse V gamma 7+ IEL, which has a high degree of amino acid sequence homology with the human V gamma 8 protein.

Adult↗
PubMed1994

Formoterol and salmeterol are both long acting compared to terbutaline in the isolated perfused and ventilated guinea-pig lung.

An isolated, perfused and ventilated guinea-pig lung was used to compare the duration of effect of the bronchodilating beta 2-adrenoceptor agonists formoterol, salmeterol and terbutaline. Lung conductance was measured real time with the aid of a computer. Bronchoconstriction was induced in the preparation every 10 min by bolus injections of acetylcholine into the pulmonary artery. Lung conductance was reduced by about 70% after acetylcholine. The test compounds or the vehicle was administered for 1 min as aerosols generated from solutions: formoterol (10 mumol/l), salmeterol (100 mumol/l) and terbutaline (1000 mumol/l). This treatment inhibited the response to acetylcholine by 50-60% within the first 10 min for all three test compounds. The onset of action appeared to be slower for salmeterol than for formoterol and terbutaline. The inhibitory effect of terbutaline disappeared completely during the next 20 min of continuous perfusion (single pass), while both formoterol and salmeterol displayed a significant inhibitory effect 40 min after their administration. Formoterol, when inhaled at a higher dose (100 mumol/l), caused a 90% inhibition of the response to acetylcholine. This effect was completely reversed by 0.1 mumol/l propranolol in the perfusion medium. There were in general no major changes in the basal conductance measured between the acetylcholine provocations.

Acetylcholine↗
PubMed1994

Monoamine oxidase inhibition by the MAO-A inhibitors brofaromine and clorgyline in healthy volunteers.

The present study compared the extent and duration of MAO inhibition by the selective and reversible MAO-A inhibitor brofaromine with the selective and irreversible MAO-A inhibitor clorgyline using amine pressor tests and excretion of urinary amine metabolites (MHPG, tryptamine). The pharmacological characterization of clorgyline as an irreversible and brofaromine as a reversible MAO-A inhibitor in clinically effective doses was confirmed in humans.

Administration, Oral↗