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Biomedical subjects

T E Johansen

Publications and source records attributed to T E Johansen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Analysis of the structure of empty and peptide-loaded major histocompatibility complex molecules at the cell surface.

We compared the conformation of empty and peptide-loaded class I major histocompatibility complex (MHC) molecules at the cell surface. Molecular conformations were analyzed by fluorescence resonance energy transfer (FRET) between fluorescent-labeled Fab fragments bound to the alpha 2 domain of the MHC heavy chain and fluorescent-labeled Fab fragments bound to beta 2-microglobulin. No FRET was found between Fab fragments bound to empty H-2Kb, but FRET was detected when empty H-2Kb molecules were loaded with peptide. The magnitude of FRET depended on the sequence of the peptide used. The results imply that empty H-2Kb molecules are in a relatively extended conformation, and that this conformation becomes more compact when peptide is bound. These changes, which are reflected in peptide-dependent binding of monoclonal antibodies, affect the surfaces of MHC molecules available for contact with T cell receptors and hence may influence T cell-receptor recognition of MHC molecules.

Animals↗
PubMed1994

[Contents and updating of disaster plans].

The disaster contingency plans of 62 hospitals with surgical, acute emergency functions were evaluated. Most plans were incomplete with regard to continued and extended activity or evacuation of the entire hospital in the event of war. Only 13% had adequate plans for internal accidents or situations with reduced of lost supply of vital resources such as water, medical gases or electricity. Plans for serious accidents in peacetime were to some degree deficient with regard to important aspects of the organization of the hospital in an emergency situation. Efforts to improve this crucial planning work are discussed.

Accidents↗
PubMed1994

[Form and readability of disaster plans].

We have evaluated the disaster contingency plans for 62 out of 69 Norwegian hospitals with surgical, acute emergency functions. Page volume varied from 2-115, mean 33 pages. Only nine hospitals had pocket size printed documents (A5). At the rest of the hospitals the plans had an A4-format and consisted of photocopied pages. Illustrations were few and of low quality. Too much text contained general information with no practical relevant instruction. Readability varied for different groups of health workers. Doctors received the best instructions for their tasks. Hospitals should seek professional assistance to edit, illustrate and produce the plans, and a certain degree of standardization of the plans should be aimed at. National health authorities should encourage the hospitals in this work.

Disaster Planning↗
PubMed1994

[Urinary bladder diverticula].

We describe two patients with urinary tract infection and obstructive voiding problems which lasted for respectively 21 months and five years before a bladder diverticulum was diagnosed by cystography and cystoscopy. Both patients were operated on by open diverticulectomy. The post-operative courses were uneventful and both patients were relieved of urinary symptoms after surgery. The article includes a review of the literature on bladder diverticula.

Adult↗
PubMed1994

[Antegrade stenting of the urinary tract].

Double J-catheters were placed between the renal pelvis and the urinary bladder in 20 ureters in 18 patients with impaired renal function. Retrograde catheterization via cystoscopy was impossible. The mean age of the patients was 69 years. The ureteral obstruction was a malignant tumour in 12 cases, a benign condition in three, and immediate postoperative complication in a further three patients. 11 patients were in the terminal phase of malignant disease. In six cases catheterization was accomplished by a combined antegrade and retrograde technique and a joint effort by radiologist and urologist. Antegrade placement of an internal stent is less harmful to the patient than external drainage of the renal pelvis. Large reoperations can be avoided in patients with ureteral obstruction caused by postoperative complications.

Aged↗
PubMed1994

Evidence for a common molecular mode of action for chemically distinct nonpeptide antagonists at the neurokinin-1 (substance P) receptor.

The molecular mechanism of action of three chemically distinct nonpeptide antagonists, SR 140,333, FK 888, and RP 67,580, was compared with that of the previously characterized compound CP 96,345, using a series of chimeric constructs between their common target, the rat neurokinin (NK)-1 (substance P) receptor, and the homologous nonresponsive NK-3 (NKB) receptor. The ability of all four nonpeptide compounds to displace radiolabeled substance P from the NK-1 receptor and their ability to inhibit the peptide-induced increase in inositol phosphate turnover were critically dependent on structural elements located in an area from the middle of the second extracellular loop through transmembrane segments V and VI to the middle of the third extracellular loop of the NK-1 receptor. Dissection of the domain around the outer part of transmembrane segments V and VI into smaller segments demonstrated that the individual nonpeptide antagonists, in agreement with their distinct chemical structures, were dependent on different subepitopes within the common putative binding domain. Full NK-1-like susceptibility to SR 140,333, FK 888, and CP 96,345 could be transferred to the NK-3 receptor by exchange of transmembrane segments V and VI and adjacent parts with corresponding segments from the NK-1 receptor. For SR 140,333 and CP 96,345, almost the same effect could be achieved by transfer of two discontinuous segments around the top of transmembrane segments V and VI. RP 67,580 shared interaction sites with the other compounds around the top of transmembrane segment VI but appeared also to be dependent on transmembrane segment VII. It is concluded that four nonpeptide antagonists, despite overt chemical differences, appear to block NK-1 receptor function by interacting in distinct ways with a common site located spatially around the outer part of transmembrane segment VI.

Animals↗
PubMed1993

A bladder cancer multi-institutional experience with total cystectomy for muscle-invasive bladder cancer.

BACKGROUND: The role of total cystectomy was to be assessed in the curative treatment of muscle-invasive bladder cancer. METHODS: Two hundred and fifty-three patients with T2-T4a transitional cell carcinoma of the urinary bladder were referred to precystectomy radiation therapy (46 Gy, 66 patients; 20 Gy, 187 patients). These patients represented approximately 20% of all patients developing muscle-invasive bladder cancer in Southern Norway from 1980-1990. The clinical T categorization was generally based on palpability and extent of the palpable bladder tumor assessed by the referring urologist. Twenty-six patients (10%) did not have total cystectomy, most often due to peroperatively demonstrated locoregional inoperability. Two or three cycles of cisplatin-based combination chemotherapy were given to 68 patients. RESULTS: For the 227 patients who underwent cystectomy, the cancer-specific 5-year survival rate was 58% (T2 [104 patients], 63%; greater than or equal to T3 [123 patients], 54%) (P = 0.022). The comparable figure for patients with histologically proven regional lymph node metastases was 22%. The 97 stage-reduced cases (less than or equal to pT1) survived significantly longer than the 130 patients without stage reduction (74% versus 46%) (P < 0.0001). Neoadjuvant chemotherapy was correlated with a more favorable survival in patients with greater than or equal to T3 tumors but did not seem to influence survival of patients with T2 bladder cancer. CONCLUSIONS: In a multicenter setting, prognostically relevant T categorization of operable muscle-infiltrating bladder cancer can be based on the palpability of the primary tumor. Approximately 50% of favorably selected patients with operable T2-T4 bladder cancer survived for at least 5 years independent of whether the operation was done at a large uro-oncologic unit or a smaller urologic section. In this retrospective review, chemotherapy seemed to improve the survival in patients with deeply infiltrating (greater than or equal to T3) bladder cancer but appeared to represent an overtreatment in patients with T2 tumors.

Adult↗
PubMed1993

[Retroperitoneal chylous cyst].

In pathology, cysts of the retroperitoneum are usually classified together with omental and mesenteric cysts. Because of risk of complications and malignancy these cysts should be extirpated. The frequency of complications and recurrence after surgery is significantly higher for retroperitoneal cysts than for the other types mentioned above. We describe a patient with a retroperitoneal chylous cyst of three litres. Correct diagnosis was made by CT-scan and chemical analysis of cyst fluid prior to surgery. The cyst was removed completely using an intercostal, retroperitoneal approach. The postoperative course was uneventful, and no evidence of recurrence was found after six months.

Adult↗
PubMed1993

[Cystitis cystica--a premalignant condition?].

Although cystitis cystica is considered to be a premalignant disease of the urinary bladder, remarkably few reports document the progression from cystitis cystica and glandularis to carcinoma of the bladder. We describe three patients where cystitis cystica was demonstrated 12, three and one month before diagnosis of cancer. We believe cystitis cystica reflects mobilization of the humoral immune defence mechanism in response to various agents, among these a subclinical malignant tumour.

Aged↗
PubMed1993

A soluble divalent class I major histocompatibility complex molecule inhibits alloreactive T cells at nanomolar concentrations.

Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2Kb/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2Kb, and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2Kb/IgG inhibited lysis of H-2Kb-expressing target cells not only by alloreactive H-2Kb-specific T-cell clones but also by alloreactive H-2Kb-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2Kb/IgG molecule and an H-2Kb-specific alloreactive T-cell clone. Unlabeled H-2Kb/IgG displaced 125I-labeled H-2Kb/IgG from T cells with an IC50 of 1.2 nM.

Amino Acid Sequence↗
PubMed1993

Processing of two homologous precursors, pro-neuropeptide Y and pro-pancreatic polypeptide, in transfected cell lines expressing different precursor convertases.

The processing of two homologous precursors, pro-neuropeptide Y (pro-NPY) and pro-pancreatic poly-peptide (pro-PP), was studied in four neuroendocrine cell lines after transfection: CA-77 medullary thyroid carcinoma cells, AtT-20 corticotrope pituitary cells, RIN2A-19 pancreatic endocrine cells, and NB1 neuroblastoma cells. Northern blot analysis indicated that the AtT-20 cells only expressed precursor convertase 3; in contrast, NB1 cells only expressed precursor convertase 2, whereas the RIN2A-19 and CA-77 cells expressed both enzymes. Despite these differences in expression pattern of precursor convertases the four cell lines were, surprisingly, indistinguishable in respect to their processing of pro-PP and pro-NPY. In all four cell lines, pro-NPY was almost completely converted to NPY, and, in all four cell lines, only around 50% of the PP precursor was converted to PP. The relatively poor processing efficiency of pro-PP was rather similar to the processing efficiency of the endogenously produced precursors in the respective cell lines, pro-calcitonin (CA-77), proopiomelanocortin (AtT-20), proinsulin (RIN2A-19), and pro-vasoactive intestinal polypeptide (NB1). At least in the CA-77 cells, NPY and PP were apparently sorted to the regulated secretory pathway, as upon stimulation with secretagogue the release of the transfected peptides increased in parallel with the endogenously expressed peptide, calcitonin gene-related peptide. Mutagenesis studies showed that on the N-terminal side of the di-basic processing site, the otherwise important difference in structure between PP and NPY, a proline for glutamine in position 34, was not responsible for the difference in processing efficiency. On the C-terminal side of the processing site, the efficient processing of pro-NPY could not be transferred to pro-PP by exchanging the whole C-terminal domains of the precursors. It is concluded that pro-NPY is processed more efficiently than pro-PP in all neuroendocrine cell lines tested independent on their expression of the two main precursor convertases and that mutagenesis data indicate that the structural element responsible for the efficient processing of pro-NPY is not located on the N-terminal side of the dibasic processing site.

Amino Acid Sequence↗
PubMed1993

Chimeric NK1 (substance P)/NK3 (neurokinin B) receptors. Identification of domains determining the binding specificity of tachykinin agonists.

The NK1 (substance P) and NK3 (neurokinin B) receptors are G protein-coupled receptors sharing approximately 70% identity within the membrane-spanning domains. However, they each have a distinct pharmacological profile in respect of peptide binding. To identify epitopes that determine their selectivity for natural and synthetic tachykinin peptides, we constructed a series of chimeric NK1/NK3 receptors in which carboxyl-terminal segments of increasing length in the NK1 receptor were exchanged with the corresponding segments from the NK3 receptor. The general, structural integrity of the chimeric constructs was confirmed by the amphibian tachykinin peptide, eledoisin, which was recognized equally well by both of the wild-type receptors and bound with a similar or even higher affinity to all the chimeric receptors. Competition binding studies showed that the affinity of the two natural ligands, substance P and neurokinin B, changed gradually through the series of chimeric receptors indicating that several binding epitopes throughout the receptor structure are involved in the selective recognition of these peptides. However, whereas the single, largest change in binding affinity for substance P occurred when segments in the amino-terminal end of the receptor were exchanged, this occurred for neurokinin B in the carboxyl-terminal end of the receptor. The affinity of the NK1-selective ligand, [Sar9,Met(O2)11]SP, changed even more gradually through the series of chimeric receptors than that of substance P. In contrast, the NK3-selective hexapeptide, senktide, was recognized only when transmembrane segment III and IV from the NK3 receptor were incorporated into the chimeric constructs. These data suggest that several receptor domains contribute to the binding specificity of tachykinin agonists but in varying degrees for each peptide. It is concluded that the tachykinin peptides, in partially different ways, interact with multiple epitopes scattered throughout the receptor structure, but conceivably these epitopes are closely located in space around a hypothetical receptor center.

Amino Acid Sequence↗
PubMed1993

Different binding epitopes on the NK1 receptor for substance P and non-peptide antagonist.

Non-peptide ligands for peptide receptors have been discovered in several systems through file screening programs, but the mechanism of action for these candidate drugs is obscure as they do not chemically resemble the native peptides. The compound CP 96345 is a high-affinity, non-peptide antagonist of the substance P (NK1) receptor, which is important in pain perception and neurogenic inflammation. Here we identify epitopes on the NK1 receptor responsible for the specific binding of CP 96345 by systematic exchange of corresponding segments between the NK1 receptor and the homologous NK3 (neurokinin B) receptor, which does not bind the non-peptide ligand. Non-conserved residues, in two epitopes around the top of transmembrane segment V and in one epitope at the top of transmembrane segment VI, are essential for the specific action of CP 96345 on the NK1 receptor, but are surprisingly not important for the binding of the natural peptide ligand, substance P. Susceptibility to the non-peptide antagonists can be conveyed to the previously unresponsive NK3 receptor by mutational transfer of this discontinuous epitope from the NK1 receptor.

Amino Acid Sequence↗
PubMed1993

[Urinary bladder fistulas].

During the period 1978 to 1991, 19 patients were treated for fistula of the urinary bladder, 12 of the fistulas were enterovesical, four vesicovaginal, one vesicouterine and two vesicocutaneous. Most of them occurred after diverticulitis or operation, or when the patient suffered from a malignant disease. Four patients received conservative treatment. One patient decided against an operation, two were inoperable, and one fistula closed with use of an indwelling catheter. 15 were operated on. 12 extirpations of fistula were carried out. Additional resection of intestine was performed in seven patients and hysterectomia in two patients. Other procedures included two enterostomias and one ileum bladder. In ten patients postoperative courses were uneventful. Four patients died during the first month after operation. One suffered a relapse, and another damage to the nerves of the bladder.

Adult↗
PubMed1993

Carcinoma of the urachus. A case report and review of the literature.

A 63-year-old man presented with haematuria and suprapubic pain. After transurethral resection of the prostate a tumour was seen in the bladder dome at cystoscopy. Biopsy revealed an adenocarcinoma. Based on intraoperative and histological examination of the partial cystectomy specimen, the tumour was judged to be an urachus carcinoma. Four years after diagnosis the patient has no evidence of tumour. While partial cystectomy is the most frequent treatment, a radical total cystectomy is advocated in poorly differentiated tumours.

Adenocarcinoma↗
PubMed1993

Efficient amidation of C-peptide deleted NPY precursors by non-endocrine cells is affected by the presence of Lys-Arg at the C-terminus.

Post-translational processing of peptide precursors producing amidated, biologically active peptides generally occurs in specially differentiated endocrine or neural cells. However, we have previously shown that a C-peptide-deleted precursor of neuropeptide Y (NPY1-39) in which the precursor terminates in the sequence Gly-Lys-Arg was partially amidated by the non-endocrine cell line, CHO. In the present study we show that two other non-endocrine cell lines, NIH 3T3 and BHK, also possess amidating activities and that the NPY1-39 precursor was completely converted to NPY1-36 amide by the NIH 3T3 cell line. The role of the two basic residues (Lys-Arg) in the C-terminus was studied by transfection of a construct encoding a NPY precursor terminating with glycine alone. Both the CHO and NIH 3T3 cell lines, transfected with this construct, secreted a significantly smaller fraction of NPY reactive material as amidated NPY compared to the fraction of amidated NPY secreted by the cells transfected with the NPY1-39 precursor. It is concluded that the capacity to perform C-terminal amidation appears to be a universal feature of eukaryotic cells and that the carboxypeptidase E-like enzyme influences the amidation process, beyond its known ability to remove the C-terminal basic residues.

3T3 Cells↗
PubMed1993

Clinical significance of DNA ploidy and S-phase fraction and their relation to p53 protein, c-erbB-2 protein and HCG in operable muscle-invasive bladder cancer.

DNA ploidy and S-phase fraction (SPF), determined by flow cytometry were studied in 118 patients with muscle-invasive transitional cell carcinoma (TCC) of the urinary bladder, scheduled for cystectomy after pre-operative radiotherapy (20 Gy/1 week) with or without systemic cisplatin-based neo-adjuvant chemotherapy. The correlation between these parameters and immunohistochemically demonstrated p53, c-erbB-2 and HCG was also investigated. There were 16 DNA diploid and 102 DNA non-diploid tumours. DNA ploidy was not related to the T (all 118 patients) or pN (58 patients) category, occurrence of stage reduction or cancer-related 5 years survival. Patients with high SPF tumours tended, however, to have a better prognosis than those with low SPF TCC reaching the level of significance (P < 0.05) for those patients who had high SPF tumours and received neo-adjuvant chemotherapy. Fifty-one of the tumours were p53 positive. p53 positive tumours were significantly more often found in TCC with low SPFs than in those with high SPFs. Respectively 12 and 9% of the tumours were HCG and c-erbB-2 positive, without correlation to DNA ploidy or SPF. We conclude that DNA ploidy does not represent a prognostic parameter in muscle-invasive operable bladder carcinomas. A high SPF, determined by FCM, may be helpful to identify patients with chemotherapy-sensitive TCC of the urinary bladder.

Adult↗