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Biomedical subjects

T Nilsson

Publications and source records attributed to T Nilsson.

At least 181 records · Page 10Linked to original sources
PubMed1990

Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Identification of a consensus motif for retention of transmembrane proteins in the endoplasmic reticulum.

Several families of transmembrane endoplasmic reticulum (ER) proteins contain retention motifs in their cytoplasmically exposed tails. Mutational analyses demonstrated that two lysines positioned three and four or five residues from the C-terminus represent the retention motif. The introduction of a lysine preceding the lysine that occurs three residues from the terminus of Lyt2 renders this cell surface protein a resident of the ER. Likewise, the appropriate positioning of two lysine residues in a poly-serine sequence confines marker proteins to the ER. Arginines or histidines cannot replace lysines, suggesting that simple charge interactions are not sufficient to explain the retention. The identified consensus motif may serve as a retrieval signal that brings proteins back from a sorting compartment adjacent to the ER.

Amino Acid Sequence↗
PubMed1990

Experimental complete ureteric occlusion in sheep: radionuclide renography and histopathologic findings.

Complete ureteric occlusion produces various pathophysiological changes that can be monitored externally by technetium 99m diethylenetriamine penta-acetic acid (99mTc-DTPA) diuretic renography (RDR). Being a dynamic imaging study, it reflects the function of the kidneys and the urodynamics of the urinary tract. The aim of this study was to correlate the changes in parameters of RDR with the histological changes before and after the release of complete ureteric occlusion. In 9 sheep, RDR studies were performed serially after various periods of complete ureteric occlusion (up to 7 weeks) and after release of the occlusion (up to 5 weeks). The histological changes were correlated with changes in RDR. The progressive decrease in renal flow seen on renal images and flow time-activity curves (TACs) was explained by the development of endarteritis and thrombosis of small renal arteries. The progressive decrease in the renal uptake as indicated by the percentage renal uptake and the extraction slope of TAC is related to the progressive damage to the renal parenchyma, initially affecting the collecting ducts and tubules, with increasing interstitial fibrosis in the later stages. Obstruction for 3 weeks or less was associated with moderate damage to the parenchyma from which recovery was possible. Obstruction for 7 weeks was associated with marked damage without chance of recovery. The RDR is a non-invasive technique that can be used to monitor kidney damage after various periods of complete ureteric occlusion and to predict the outcome of surgery before the release of occlusion.

Animals↗
PubMed1990

Coexpression of the platelet-derived growth factor (PDGF) B chain and the PDGF beta receptor in isolated pancreatic islet cells stimulates DNA synthesis.

Suspensions rich in pancreatic beta cells were transfected by means of electroporation or by using the liposome technique with DNA constructs coding for the B chain of platelet-derived growth factor (PDGF) and the PDGF alpha and beta receptors to induce a mitotic response in this slowly replicating cell type. Transfection with the B-chain construct induced synthesis of the PDGF B-chain homodimer (PDGF-BB) as assessed by the presence of 125I-labeled PDGF-BB competing activity in the conditioned medium of the transfected islet cells. Moreover, islet cells transfected with the PDGF beta-receptor construct exhibited increased immunofluorescence staining with a PDGF beta-receptor antibody. These cells also displayed increased 125I-labeled PDGF-BB binding compared with control transfected cells. Cotransfection with the B-chain construct or the addition of 10% fetal bovine serum or purified PDGF all induced DNA synthesis in islet cells transfected with the PDGF beta-receptor construct. Islet cells transfected with the PDGF alpha-receptor construct did not respond with stimulation of [3H]thymidine incorporation to any of the PDGF isoforms (PDGF-AA, -AB, or -BB). Cotransfection of the PDGF alpha- and beta-receptor constructs resulted in a loss of the DNA synthesis response to PDGF. The beta cells exhibited elevated levels of [3H]inositol trisphosphate after transfection with the B-chain and beta-receptor constructs, indicating activation of phospholipase C. Islet cells transfected with the different receptor constructs exhibited different patterns of tyrosine phosphorylation upon ligand activation. The results demonstrate that pancreatic islet cells can be stimulated to increase DNA synthesis by transfection with the PDGF beta-receptor gene, whereas cotransfection with the alpha-receptor gene may attenuate the growth response.

Animals↗
PubMed1990

An inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in liver nuclei.

Recent studies in our laboratory have revealed the existence of an ATP- and calmodulin-dependent Ca2+ uptake system in rat liver nuclei that can promote increases in the free Ca2+ concentration in the nuclear matrix. In the present investigation we show that liver nuclei possess a marked ability to sequester and buffer Ca2+, suggesting a potential role for the nucleus in the regulation of the cytosolic free Ca2+ concentration. In addition, we demonstrate that the intracellular messenger, inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3], stimulates the release of a fraction of the nuclear Ca2+ and transiently lowers the intranuclear free Ca2+ concentration. The Ins(1,4,5)P3-stimulated Ca2+ release is followed by Ca2+ reuptake into an inositol phosphate-insensitive nuclear compartment. Together, these results demonstrate that liver nuclei contain, at least, two Ca2+ pools, one of which is releasable by Ins(1,4,5)P3. These findings are consistent with a role for the nucleus in the modulation of the cytosolic free Ca2+ level by agonists and suggest that the control of the nuclear Ca2+ load by second messengers may participate in the regulation of intranuclear Ca2(+)-dependent processes by hormones and other agents.

Animals↗
PubMed1990

99mTc DTPA diuretic renography in the evaluation of surgery in chronic schistosomal and non-schistosomal obstructive uropathy.

The selection of patients with chronic obstructive uropathy for surgery is difficult because of problems in identifying true obstruction in a grossly dilated urinary tract. This is especially so in schistosomal (bilharzial) obstructive uropathy. A prospective study of 90 patients (68 with chronic schistosomal and 22 with non-bilharzial obstructive uropathy) was carried out. All patients underwent pre-operative and post-operative radionuclide 99mTc DTPA diuretic renography (RDR). The aims were to assess the value of RDR in the pre- and post-operative management of these patients and whether it could predict the outcome of surgery. Distinctive renogram patterns were identified in patients who required surgical management. These were found useful in monitoring the results and in predicting the outcome of surgery.

Humans↗
PubMed1990

A 16-year-old girl with invasive carcinoma of the vulva.

We present a 16-year-old girl with vulvar squamous cell carcinoma. The patient initially received a radical treatment because of lymph-node dissemination. However, recurrent disease erupted a little more than one year after the initial treatment, with metastases in the right lung and multiple osteolytic skeletal metastases. Despite aggressive treatments with chemotherapy the patient died about 2 years after the initial diagnosis. An aggressive radical treatment must be chosen for cases of invasive vulvar carcinoma, irrespective of the patient's age.

Adolescent↗
PubMed1990

Value of intercondylar notch plasty. CT studies and peroperative measurements of 127 knees.

The intercondylar notch diameter was measured in six knees on CT scans before and after anterior cruciate ligament reconstruction. During the operation, direct measurements of the anterior notch diameter was also performed before and after notch plasty. There was good agreement between CT and peroperative measurements, showing that the enlargement of the intercondylar notch can be measured on the CT scan. Twenty-one patients previously reconstructed because of old anterior cruciate ligament injuries were reexamined after a median of 4 years, and their notch diameters were measured by CT or at reoperation. The notch remained open in stable knees, but was narrowed in unstable knees. The notch diameter before notch plasty was assessed with a calliper at operation on 45 patients with acute and 60 patients with old injuries. Both groups had a mean intercondylar diameter of 16 mm. The conclusion that the notch plasty stays open in stable knees emphasizes the importance of this step in the reconstruction procedure.

Adult↗
PubMed1990

A simple index for assessment of disease activity in patients with ulcerative colitis.

Based upon data from a prospective series of 61 patients with ulcerative colitis, most of them with the mild or quiescent form, a simple index for assessment of the disease's activity was devised. The activity index was the sum of three different scores evaluating history, macroscopic findings at endoscopy and microscopic findings in biopsy specimens, respectively. The index was consistent in itself and it may be of value in assessing spontaneous or drug-dependent variations in ulcerative colitis. The serum protein C1 inhibitor, belonging to the acute phase reactants, could not be shown to correlate significantly with the activity index or any of its components.

Adult↗
PubMed1990

The predictive value of Tc-99m DTPA renography in obstructive uropathy using animal model.

There is no simple analytical test. Radionuclide diuretic renography (RDR), being a dynamic imaging study reflecting the function of the kidney and the urodynamics of the urinary tracts, has the potential to predict the outcome of surgery in obstructive uropathy. In 12 sheep, we occluded one ureter for a maximum of seven weeks and followed up for a maxim of five weeks after release of occlusion. Repeated Tc-99m DTPA diuretic renography studies were performed and the results were correlated with the duration of complete ureteric occlusion. The renal uptake percentage and the extraction slope of the time activity curve (TAC) showed progressive and steady decrease over the period of the occlusion. By the fifth week there was very low uptake (less than 18%) and the TAC was almost flat, suggestive of severe nephropathy. The parenchymal transit time index (PTTI) showed immediate rise after occlusion but with no progressive increase in its value. By the fifth week it dropped down to normal. After release, the recovery of function showed good correlation with the renal uptake percentage and extraction slope of TAC before release of occlusion. Therefore both these parameters, rather than PTTI, can be used to predict the outcome of surgery before the release of complete obstruction of the ureter.

Animals↗
PubMed1989

Activation of protein kinase C assists insulin producing cells in recovery from raised cytoplasmic Ca2+ by stimulating Ca2+ efflux.

The effects of protein kinase C (PKC) activation on the cytoplasmic free Ca2+ concentration ([Ca2+]i) were studied in clonal insulin-producing RINm5F cells, using the fluorescent Ca2+ indicators quin-2 and fura-2. Both under basal and stimulatory conditions PKC activation lowered [Ca2+]i in these cells by promoting an active extrusion of Ca2+ to the extracellular space. PKC activation therefore assists insulin-producing cells in recovery from raised [Ca2+]i. Such an effect might be part of the signal regulating the insulin secretory process.

Animals↗
PubMed1989

Effects of protein kinase C activation on the regulation of the stimulus-secretion coupling in pancreatic beta-cells.

Effects of protein kinase C (PKC) activation on the insulin-secretory process were investigated, by using beta-cell-rich suspensions obtained from pancreatic islets of obese-hyperglycaemic mice. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), which is known to activate PKC directly, the muscarinic-receptor agonist carbamoylcholine and high glucose concentration enhanced the phosphorylation of a specific 80 kDa PKC substrate in the beta-cells. At a non-stimulatory glucose concentration, 10 nM-TPA increased insulin release, although there were no changes in either the cytoplasmic free Ca2+ concentration ([Ca2+]i) or membrane potential, as measured with the fluorescent indicators quin-2 and bisoxonol respectively. At a stimulatory glucose concentration TPA caused a lowering in [Ca2+]i, whereas membrane potential was unaffected. Despite the decrease in [Ca2+]i, there was a large stimulation of insulin release. Addition of TPA lowered [Ca2+]i also in beta-cells stimulated by tolbutamide or high K+, although to a lesser extent than in those stimulated by glucose. There was no effect of TPA on either Ca2+ buffering or the ability of Ins(1,4,5)P3 to release Ca2+ in permeabilized beta-cells. However, the phorbol ester inhibited the rise in [Ca2+]i in response to carbamoylcholine, which stimulates the formation of InsP3, in intact beta-cells. Down-regulation of PKC influenced neither glucose-induced insulin release nor the increase in [Ca2+]i. Hence, although PKC activation is of no major importance in glucose-stimulated insulin release, this enzyme can serve as a modulator of the glucose-induced insulin-secretory response. Such a modulation involves mechanisms promoting both amplification of the secretory response and lowering of [Ca2+]i.

Animals↗
PubMed1989

Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulum.

The adenoviral transmembrane E3/19K glycoprotein is a resident of the endoplasmic reticulum. Here we show that the last six amino acid residues of the 15-membered cytoplasmic tail are necessary and sufficient for the ER retention. These residues can be transplanted onto the cytoplasmic tail of other membrane-bound proteins such that ER residency is conferred. Deletion analysis demonstrated that no single amino acid residue is responsible for the retention. The identified structural motif must occupy the extreme COOH-terminal position to be functional. An endogenous transmembrane ER protein, UDP-glucuronosyltransferase, also contains a retention signal in its cytoplasmic tail. We suggest that short linear sequences occupying the extreme COOH-terminal position of transmembrane ER proteins serve as retention signals.

Adenovirus E3 Proteins↗
PubMed1989

Transfection of insulin-producing cells with a transforming c-Ha-ras oncogene stimulates phospholipase C activity.

Pancreatic islet beta-cells and insulin-producing RINm5F cells were electroporated in the presence of the c-Ha-ras oncogene, to assess the possible involvement of the encoded product in coupling extracellular receptors to phospholipase C. After two days the c-Ha-ras-transfected cells increased their expression of c-Ha-ras mRNA. These cells were also found to contain more [3H]InsP3, suggesting an increased basal (non-ligand-activated) phospholipase C activity. In addition, the transfected cells were unable to respond to ligand (bombesin) activation of phospholipase C. The ras-transfected insulin-producing cells showed enhanced phosphorylation of a 200 kDa substrate crossreacting with an antibody to an 80 kDa protein kinase C substrate. The phorbol ester 12-O-tetradecanoyl 13-acetate and bombesin also induced phosphorylation of the 200 kDa substrate. All of these changes occurred without changes in the rates of [3H]thymidine incorporation. The results suggest that the mutated c-Ha-ras oncogene directly or indirectly stimulates the basal phospholipase C activity of these cells.

Animals↗
PubMed1989

Glucose-stimulated efflux of fura-2 in pancreatic beta-cells is prevented by probenecid.

Fura-2 loaded pancreatic beta-cells, isolated from obese hyperglycemic mice, were studied with respect to cytoplasmic free Ca2+ concentration ([Ca2+]i), insulin release and efflux of indicator. In the absence of glucose there was a continuous efflux of fura-2, which was markedly increased by stimulation with a high concentration of the sugar. Probenecid both reduced basal efflux of fura-2 and prevented that promoted by glucose. There was no interference of the drug with glucose-induced either insulin release or rise in [Ca2+]i. When applying fura-2 in pancreatic beta-cells, the use of probenecid markedly improves the measurements of [Ca2+]i.

Animals↗