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Biomedical subjects

T E Johansen

Publications and source records attributed to T E Johansen.

At least 19 recordsLinked to original sources

Major histocompatibility complex conformational epitopes are peptide specific.

Serologically distinct forms of H-2Kb are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire.

Amino Acid Sequence

[Ureteral obstruction by the pregnant uterus].

Dilatation of the upper urinary tract occurs in more than 80% of pregnant women during the last half of pregnancy. It is caused by compression of the ureter between the growing uterus and linea terminalis. A few patients develop pathological dilatation, flank pain and impaired renal function, a so-called symptomatic hydronephrosis. We have treated ten patients by means of internal drainage by using double pigtail catheters. Nine patients were completely relieved of their symptoms, and one reported marked reduction of pain. Five women complained of irritation of the bladder. In three of the women the intravesical portion of the catheter was shortened with success. Eight women kept the stent up to the time of birth. Two were removed two and eight weeks before delivery because of infection. There were no serious complications. Use of double pigtail catheters is a safe and simple way of treating symptomatic hydronephrosis of pregnancy.

Adult

[Medical and nursing leadership in hospitals. Tasks and experiences].

During winter 1991, 60% of medical and nursing administrators in Telemark county made an extensive evaluation of their own jobs. Head of Department physicians spent 60% of their working time on medical tasks, 10% on budgets and accounting, and 30% on care of the staff. Direct work in connection with patients took 48% of time. 19% of the working time was spent on secretarial functions which could preferably be delegated to others. Head of Department doctors have too little education in budgeting and accounting. Head of Section doctors spent 77% of their working time on medical tasks. This is a group of contented and productive physicians. Head of Department nurses spent 74% of their time on administrative tasks and 11% on work directly connected to patients. 25% of the time was spent on individual care of colleagues in addition to professional instruction, and the group would like to have even more time for this task. Head of Ward nurses spent 38% of their working time on patients and 58% on tasks connected to the staff. 26% of their time is mere secretarial work. Individual care of colleagues required 21% of their time, and they would like to have even more time for this purpose. All groups of administrators would like to receive more feedback from the top management of their hospital.

Attitude of Health Personnel

Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells.

Stable CHO cell clones which selectively express all three rat tachykinin receptors were established by transfection. The binding of radiolabled substance P and neurokinin A (substance K) to CHO clones expressing the NK1 and NK2 receptors, respectively, were saturatable and of high affinity (Kd = 0.17 nM (NK1); 3.4 nM (NK2)). Scatchard analysis of the binding data indicated for both receptors binding to a single population of binding sites, and competition binding studies showed that the binding specificities of the receptors corresponded to those of classical NK1 and NK2 receptors. In contrast, the binding of eledoisin to the NK3 receptor expressed in the transfected CHO cells was of low affinity (IC50 = 240 nM) compared to the high affinity of the receptor found when it was transiently expressed in COS-7 cells (IC50 = 8 nM). However, in both cases the receptor exhibited the specificity of a classical NK3 receptor. The established cell clones may provide an important tool for further analysis of the molecular mechanisms involved in binding, activation, and coupling of receptors for tachykinin peptides.

Animals

[Surgical treatment of ileus in the radiation-injured intestine].

Between the years 1977 to 1990, ten patients were operated for ileus due to intestinal damage induced by radiotherapy. The patients had received an average radiation dose of 50.2 GY. Average lapse of time between radiotherapy and operation for ileus was 15.5 months. The operation procedures included were five lysis of adhesions, four by-pass operations, three small intestine resections, one large intestine resection, three transversostomies and one ileostomy. Three patients suffered postoperative complications; one got bronchopneumonia, one suffered prolonged paralytic ileus and one suffered anastomotic leakage, sepsis and fistula formation. Five of the patients have died from their malignant illness. For the five remaining patients the observation time varies from six months to 13 years.

Adult

[Bladder rupture after minor trauma].

Rupture of the urinary bladder is a rare injury most often encountered after severe trauma and in conjunction with injuries to other organ systems. It may occur, however, without concomitant injury and also after minimal trauma. This diagnosis must be suspected in a patient with abdominal pain who is unable to void or who presents hematuria. The diagnosis is made by means of a retrograde cystogram using 350-400 ml contrast medium and supplemented by a drainage film. Intraperitoneal ruptures should be treated surgically by closure in layers, and drainage. Patients with extraperitoneal ruptures can safely be treated with simple catheter drainage until the rupture has healed, usually within 10-20 days. We report three cases of bladder rupture after minimal trauma and describe the state of the art of diagnosis and treatment of these injuries.

Adult

Processing of pro-CGRP in a rat medullary thyroid carcinoma cell line transfected with protease inhibitors.

A rat medullary thyroid carcinoma cell line, CA77, was used to study the effect of a series of biosynthesized protease inhibitors on the proteolytic cleavage of the endogenously synthesized pro-CGRP. This cell line efficiently converted the pro-CGRP to mature CGRP as assessed by chromatography of cell extracts followed by radioimmunoassay for CGRP. CA77 cells were transfected with expression vectors encoding protease inhibitors: the Arg-serpins, alpha 1-antitrypsin Pittsburgh (358 Met----Arg) and plasminogen activator inhibitor 1, the Kazal type serine protease inhibitor, pancreatic secretory trypsin inhibitor, and the general thiol protease inhibitor, cystatin C. Only the chromatography of cell extracts from CA77 cells transfected with a plasmid encoding cystatin C showed an apparent higher content of unprocessed pro-CGRP as compared to non-transfected cells. No effect on pro-CGRP processing could be measured in the CA77 cells transfected with plasmids encoding the three serine protease inhibitors. CA77 cells were also transfected with two constructs encoding chimeric proteins consisting of cystatin C and the precursor for neuropeptide Y. Release experiments using 8-bromo cAMP as the secretagogue showed that the chimer was co-released with CGRP. However, no effect of this chimer upon pro-CGRP processing could be detected. It is concluded that the processing of pro-CGRP in the CA77 cell line was very efficient and that four different protease inhibitors and two cystatin C/NPY chimers synthesized by this neuroendocrine cell line had only minimal effect upon the processing of CGRP.

Animals

Hospitalisation of prostatic cancer patients undergoing orchiectomy.

We report our experience with 100 orchiectomies for advanced prostatic cancer in hospitalised patients. Approximately 60% of the patients required hospitalisation for additional treatment and investigation of complications due to their disease at the time of orchiectomy. In 51 cases the orchiectomy was combined with transurethral resection of the prostate (TURP); 37 patients had pathological levels of serum creatinine and 17 had pathological dilatation of the upper urinary tract, 6 of whom required a nephrostomy catheter. Because of anaemia on admission, 21 patients received a peri-operative blood transfusion. Two patients had significant post-operative bleeding, 2 developed a wound infection and 1 had a deep thrombophlebitis. The patients' mean age was 76.4 years and the period of hospitalisation ranged from 3 to 150 days with peaks at 3 and 8 days. The most important reason for prolonged hospitalisation was social problems. It was concluded that many patients who were hospitalised as a direct consequence of their prostatic carcinoma would have been in hospital for a similar period regardless of the method of hormonal manipulation used. Because so many patients have other reasons for hospitalisation, or require additional surgical procedures such as TURP, the true average cost of orchiectomy for advanced prostatic cancer is difficult to determine.

Aged

CHO cells synthesize amidated neuropeptide Y from a C-peptide deleted form of the precursor.

Post-translational processing of peptide precursors producing amidated, biologically active peptides is generally believed to occur only in specially differentiated endocrine or neural cells. Previously it has been shown that endoproteolytic processing of peptide precursors is very inefficient in non-endocrine cells like CHO cells. We have studied the processing of a C-peptide-deleted precursor of neuropeptide Y (NPY) in which the precursor terminates in the sequence Gly-Lys-Arg and does not require any dibasic specific endoproteolytic processing. Following transfection of CHO cells with an expression plasmid encoding this mutated NPY precursor, between 50 and 80 percent of the synthesized NPY was secreted from stable transfectants as authentic amidated NPY as assessed by both a C-terminal amide specific radioimmunoassay and by isoelectric focusing. It is concluded that amidated peptides can be produced in non-endocrine cells provided they are presented with a precursor which does not have to be endoproteolytically processed.

Amino Acid Sequence

C-terminal KDEL-modified cystatin C is retained in transfected CHO cells.

The significance of a C-terminal tetrapeptide, Lys-Asp-Glu-Leu (KDEL), as a retention signal for the endoplasmatic reticulum was studied using cystatin C, a general thiol protease inhibitor, as the reporter protein. Clones of CHO cells were analyzed after stable transfection with eukaryotic expression vectors encoding either cystatin C, KDEL extended cystatin C, or cystatin C extended with a control sequence. It is concluded that cystatin C with the KDEL tetrapeptide as a C-terminal extension is retained intracellularly without apparent accumulation of the molecule.

Amino Acid Sequence

[Clinical research--relations of central and peripheral hospitals].

Clinical research is of great importance for the patients, the medical industry, doctors, hospitals and society as a whole. More time should be set aside for clinical research during (daily) working hours. Arrangements should be made to stimulate and guide young colleagues who have new ideas, through scientific projects at whatever hospital they work. Depending on economy and the doctors' qualifications, central and peripheral hospitals should cooperate on clinical research. Although their hospitals are of different size, the doctors are equally capable and cooperation is characterized by colleagual interdependence.

Hospitals

Biosynthesis of peptide precursors and protease inhibitors using new constitutive and inducible eukaryotic expression vectors.

A series of expression vectors has been constructed as based on the pML derivative of pBR322. The eukaryotic transcription units employ various promoters followed by polycloning sites for 3-9 commonly used restriction enzymes and are completed by the SV40 polyadenylation sequence. In 4 of the vectors, designed for co-transfection or transient expression studies, only a single transcription unit containing either a constitutive or an inducible promoter was incorporated. The human ubiquitin (UbC) promoter was used as a strong constitutive promoter, while the mouse metallothionein promoter and the promoter of the long terminal repeats of the mouse mammary tumor virus were used as inducible promoters. Another vector contained an additional transcription unit encoding a eukaryotic selection marker, the neomycin resistance encoding gene. The vectors were used in CHO cells and in neuroendocrine CA77 cells to synthesize peptide precursors, protease inhibitors and a protease. It is shown that these vectors are very efficient for the constitutive and inducible expression of nucleotide sequences in both transient and stable transfections of eukaryotic cells.

Animals

[Urothelial carcinoma of the upper urinary tract. 10 years' material from a central hospital].

During the last ten years, 16 patients have been treated for urothelial carcinoma of the upper urinary tract, ten carcinomas of the renal pelvis and six carcinomas of the ureter. Mean age at the time of diagnosis was 64.3 years. The most common symptoms were hematuria, flank pain and loss of weight. The diagnosis was established by intravenous pyelography and retrograde ureteropyelography. Ureteral carcinomas were operated with local resection of the ureter, while carcinomas of the renal pelvis were treated with a nephroureterectomia. Most tumours were highly malignant. Four tumours were non-invasive and, in retrospect, could have been treated with a local resection only. Only 35% of patients with urothelial carcinoma in the upper urinary tract are alive five years after diagnosis.

Adult

[Medical or surgical castration in prostatic cancer? Experience of 100 orchiectomies].

The mean age of 100 patients who underwent orchiectomy for carcinoma of the prostate was 76.4 years. 50% of the patients had distant metastases. Almost all had a locally advanced tumour. 49 patients were operated by orchiectomy only. On 51 occasions, a transurethral resection of the prostate was carried out under the same anesthesia. In 22 patients, operation of the prostate was done without previous planning, "because the patient was already on the operating table". Mean stay in hospital varied from 11.2 to 15.6 days, depending on the extent of the operative treatment. Social factors were the most important reason for prolonged hospitalization. Patients who are offered castration in the treatment of prostatic cancer have a great latent need for medical service and social care.

Aged

Testicular histology after treatment with LH-RH analogue for carcinoma of the prostate.

Orchiectomy was performed in 16 patients because of progression of prostatic cancer despite adequate medical castration with goserelin (Zoladex, ICI) over a mean period of 17.6 months. Severe tubular atrophy was seen in the testes. The Leydig cells also showed signs of atrophy, a fact that may indicate a direct effect of goserelin on these cells. In 1 patient, however, orchiectomy was postponed for 3 months after cessation of medical castration. The serum testosterone had resumed almost normal values and testicular histology revealed intact spermatogenesis and apparently normal Leydig cells.

Aged

[Ultrasonic diagnosis of undescended testes. Methods and possibilities].

83 boys with 123 empty hemiscroti were assessed by clinical examination and ultrasound. After repeated clinical examination with the patient in general anesthesia 60 undescended testes were operated. We present the technical aspects of examination of undescended testes by ultrasound. When testicular position as established by ultrasound was compared with intraoperative finding position, ultrasound had a very high sensitivity, specificity and accuracy for testes positioned distal to the internal ring. The anatomical position of the testis at sonography and the patient's age provide objective evidence to discern retractile and truly undescended testes.

Child