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Biomedical subjects

O Jansson

Publications and source records attributed to O Jansson.

At least 19 recordsLinked to original sources

Working capacity and resting energy expenditure after ileal pouch-anal anastomosis.

BACKGROUND: The aim was to evaluate the working capacity and resting energy expenditure in patients who had undergone restorative proctocolectomy. METHODS: Of 72 patients operated on between April 1990 to September 1998, 51 were eligible and 38 participated in the study. Resting energy was assessed by indirect calorimetry, and working capacity by ergospirometry on an exercise bicycle. RESULTS: The median functional score was 2 (range 0-7). Oxygen uptake during rest was reduced for men compared with predicted values. The corresponding values for women were in keeping with predicted values. The median working capacity was 96 (range 59-102) per cent for women and 91 (range 51-113) per cent for men, compared with reference values of maximum workload based on age, height and sex. There was no correlation between functional score and any other variable measured. CONCLUSION: Patients who have undergone restorative proctocolectomy for ulcerative colitis have normal resting energy expenditure and working capacity.

Adult↗

C-peptide binding to human cell membranes: importance of Glu27.

In addition to its established role in proinsulin folding, C-peptide has a function in regulation of cellular activity. The 31-residue peptide influences renal, vascular, and metabolic functions in patients with insulin-dependent diabetes mellitus. Binding to cells has been demonstrated for C-peptide, which can be displaced by its C-terminal pentapeptide. We have now used fluorescence correlation spectroscopy to investigate structural requirements on the pentapeptide part for C-peptide binding. All pentapeptide residues, E(27)GSLQ(31), were individually replaced with Ala and the capacity of the resulting peptides to displace rhodamine-labelled full-length human C-peptide from human renal tubular cell membranes was determined. This showed that Glu27 is essential for displacement, while replacement of Gly28 with Ala has little effect, and replacement of any of the three most C-terminal residues had intermediate effects. Morevover, free Glu displaces full-length C-peptide to about 50%, while free Ala, C-peptide(1-26), and the truncated pentapeptide, corresponding to the tetrapeptide G(28)SLG(31), have no displacing capacity. The peptides EVARQ (corresponding to the rat C-terminal pentapeptide) and ELGGGPGAG (corresponding to positions 11-19 of human C-peptide) do not displace human C-peptide. These results indicate that Glu27 of C-peptide is critically involved in binding to cellular targets.

Alanine↗

p53 mutations in urinary bladder cancer.

We have screened for mutations in exons 5-8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b-G4 or > or = T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant.

Cell Differentiation↗

Low interleukin-1alpha messenger RNA levels predict decreased overall survival time of patients with urinary bladder carcinoma.

Due to our inability to exactly characterize tumours, many patients with urinary bladder cancer undergo unnecessary surgery or cytostatic therapy. We have here studied the expression of the cytokine interleukin-1alpha (IL-1alpha ) in 73 human bladder carcinomas in relation to patient survival, and examined possible relationships between IL-1alpha and urokinase plasminogen activator (uPA) expression. Expression levels of IL-1alpha and uPA mRNA were determined by RT-PCR using the quantitative TaqMan technique. The levels of IL-1alpha mRNA expression did not differ significantly between tumours of different grade or stage. Calculation of the overall survival rates showed a decreased overall survival time for patients with low levels of IL-1alpha mRNA in their tumours (log rank; P = 0.0002, median follow up: 37 months). Low tumoral IL-1alpha expression predicted decreased survival of patients with poorly differentiated tumours (P< 0.005) and of patients with invasive tumours (P = 0.02). uPA expression was about 4-fold increased in poorly differentiated tumours. High levels of uPA mRNA were associated with decreased overall survival times (log rank; P = 0.032, n = 60). We conclude that IL-1alpha is important for bladder cancer biology, and that measurements of this cytokine may be useful in pre-treatment characterization of urinary bladder cancer.

Cohort Studies↗

Combination of biomolecular interaction analysis and mass spectrometric amino acid sequencing.

We describe an approach for the combination of biomolecular interaction analysis (BIA) and electrospray tandem mass spectrometry (ESI/MS/MS) to obtain sequence information on the affinity-bound proteins on the sensor chip of BIA. The procedure is illustrated with stable and unstable interactions of recombinant proteins, i.e., histidine-tagged protein-Ni2+/NTA and 1,4,5-inositol trisphosphate receptor-ligand interactions. The E. coli lysates expressing the recombinant proteins were passed through the sensor chips, and biomolecular interactions were monitored in real time. The molecules detected on the sensor chip were digested by delivering proteolytic enzyme to the sensing flow cells. The resulting on-chip digested peptide mixture at the mid- to low-femtomole level was recovered on a microcapillary reversed-phase precolumn by an on-line system and analyzed using HPLC-MS/MS. In both cases, unambiguous sequence information on the recombinant proteins isolated on the sensor chip was obtained from only a single run of analysis. The combined BIA-MS/MS may prove to be a general and versatile system to discover novel biomolecular interactions and to analyze protein complexes.

Calcium Channels↗

Sutureless small bowel anastomoses: experimental study in pigs.

OBJECTIVE: To evaluate a new technique for experimental anastomosis with fibrin glue, and to compare the results with those of stapled and one-layer sutured anastomosis. DESIGN: Open laboratory study. SETTING: Teaching hospital, Sweden. ANIMALS: Ten Swedish domestic pigs. INTERVENTIONS: Each pig had three anastomoses made in the small bowel, one by each technique. The pigs were killed on the 4th postoperative day. MAIN OUTCOME MEASURES: Blood flow, collagen concentration, anastomotic index, breaking strength, thickness of bowel wall, and histological appearance. RESULTS: Two pigs died postoperatively, leaving 8 for analysis. The blood flow at each anastomotic site studied by the microsphere technique was similar irrespective of the type of anastomosis (p = 0.3), as was anastomotic collagen concentration (p = 0.09). The anastomotic index, however, was significantly higher in the stapled than in the glued or sutured ones (p = 0.03). The glued anastomosis was the weakest, being only one fifth the strength of the stapled and one third the strength of the sutured anastomosis. There was no sign of rejection of the glue (of human origin) on histological examination. Glued and stapled anastomoses showed signs of mild inflammation, which did not reach the intensity of that around the sutured anastomoses. CONCLUSION: It is possible to make a sutureless anastomosis that does not leak with a modified stapler using fibrin glue instead of staples, but the anastomosis has considerably lower breaking strength than either stapled or sutured anastomoses.

Anastomosis, Surgical↗

Combining MALDI mass spectrometry and biomolecular interaction analysis using a biomolecular interaction analysis instrument.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been combined with biomolecular interaction analysis (BIA) in a Biacore instrument. A method has been developed for the recovery of the affinity-bound molecules from the sensor chip in a few microliters ready for mass spectrometric analysis. The procedure is illustrated with two molecular systems which exemplify antibody-antigen and DNA-protein interactions. In both cases, femtomole quantities of the affinity-bound proteins were eluted and subsequently detected by MALDI-MS. Whereas the Biacore analysis yields the surface concentration of protein bound to the sensor chip, identity of the bound compounds is revealed in the second step by accurate molecular mass determination. Combining the information of the two analyses allows calculation of the total surface molar concentration of affinity-bound molecules.

Antigen-Antibody Reactions↗

Increased colonic permeability in patients with ulcerative colitis: an in vitro study.

BACKGROUND: Colonic permeability was studied in vitro in patients subjected to colectomy because of ulcerative colitis and in control patients undergoing colonic resections for cancer. METHODS: The mucosal layer from fresh colonic segments was stripped and mounted in Ussing diffusion chambers containing modified Krebs buffer solution. The mucosa to serosa passage of the marker molecules 14C-mannitol and ovalbumin was measured for 120 min. RESULTS: Marker passage was significantly increased in colitis patients compared with control patients, irrespective of age, sex, duration of disease, and treatment. Marker passage was further increased in patients with acute colitis. The increased colonic permeability may be explained by inflammation and the resultant loss of mucosal integrity. The increased permeability to ovalbumin implies that permeability to luminal macromolecules, such as bacterial products and other antigenic substances, might be increased in colitis. CONCLUSIONS: The results suggest a derangement of the colonic barrier, as evidenced by an increased mucosal permeability in both chronic and acute colitis.

Adolescent↗

Surface plasmon resonance biomolecular interaction analysis mass spectrometry. 2. Fiber optic-based analysis.

Fiber optic probe-based surface plasmon resonance (SPR) detection has been used in combination with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the rapid, sensitive, and selective detection of biomolecules. SPR was used to monitor the covalent immobilization of a polyclonal antibody to the surface of a fiber optic probe. The derivatized probe was then used for the selective detection (from solution) of the corresponding antigen and a secondary antibody directed toward the antigen. Species retained during the SPR detection process were next analyzed by direct MALDI-TOF analysis of the probe surface (after exposed to the MALDI matrix and introduction into the mass spectrometer). The combined approach allowed for the two-dimensional detection of biomolecules, with SPR analysis yielding quantitative information pertinent to the binding events and MALDI-TOF providing details on the qualitative nature of the binding partners.

Animals↗

Surface plasmon resonance biomolecular interaction analysis mass spectrometry. 1. Chip-based analysis.

The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) in concert with surface plasmon resonance-based biomolecular interaction analysis (SPR-BIA) is reported. A chip-based biosensor unit was used to simultaneously monitor biomolecular interactions taking place on four different regions of the sensor chip (flow cells). Species retained during SPR-BIA were then identified by performing MALDI-TOF directly from within the area of the flow cells. Analyses were performed on an antibody/antigen/antibody system with detection limits in the low-femtomole range. The combined assay demonstrates the use of SPR-BIA to evaluate the relative stability of sequential solution-phase interactions, as well as, upon MALDI-TOF analysis, the ability to unambiguously confirm the presence of species retained during the interaction analysis.

Animals↗

Elevated nitric oxide in the urinary bladder in infectious and noninfectious cystitis.

OBJECTIVES: A role for nitric oxide (NO) has been suggested in inflammation and host defense. At higher concentrations, this gas shows cytotoxic effects that may be directed against microorganisms, tumor cells as well as host cells. The aim of the present study was to study the relationship between bladder mucosal inflammation and local production of NO. METHODS: We measured NO directly in the urinary bladder in patients with infectious cystitis, interstitial cystitis, irradiation cystitis, and cystitis induced by antitumor treatment with bacillus Calmette-Guérin. NO-free air was introduced into the bladder during cystoscopy. The air was aspirated after 5 minutes of incubation and injected into a chemiluminescence NO analyzer. RESULTS: NO levels were 30 to 50 times higher in all varieties of cystitis as compared to controls. CONCLUSIONS: NO may contribute to host-defense mechanisms in the bladder during bacterial infection and antitumor treatment. Direct measurement of gaseous NO in the urinary bladder seems to be an attractive diagnostic method for detection of mucosal inflammation.

Aged↗

Calcium-independent and steroid-resistant nitric oxide synthase activity in human paranasal sinus mucosa.

Nitric oxide (NO) is present in the human nasal airways and originates primarily from the paranasal sinuses. Immunohistochemical studies and messenger ribonucleic acid (mRNA) in situ hybridization indicate that a type-2 NO synthase (NOS) is constitutively expressed in healthy sinus epithelium. We have further characterized sinus NOS activity by studying the enzymatic conversion of L-arginine to L-citrulline in biopsies from sinus mucosa. Maxillary sinus biopsies were obtained from nine healthy subjects during reconstructive facial surgery. In addition, nasal NO concentrations in nine controls were compared with those found in five patients treated with high systemic doses of glucocorticosteroids. Finally, the effects of i.v. L-arginine infusion on nasal cavity NO concentrations were studied in six healthy subjects. Ca(2+)-independent NOS activity was found in all biopsies and was five times higher than Ca(2+)-dependent activity (179 +/- 64 and 36 +/- 17 pmol.g-1.min, respectively). There was no difference in nasal NO levels between controls (344 +/- 21 parts per billion (ppb)) and steroid-treated patients (342 +/- 36 ppb). Nasal NO levels increased up to 35% following i.v. infusion of L-arginine. We conclude that NOS activity in healthy sinus mucosa is predominantly Ca(2+)-independent and this NOS is not downregulated by systemic steroids. Furthermore, L-arginine infusion increases nasal airway NO excretion in vivo, indicating that the substrate concentration is a rate-limiting factor under basal conditions. These findings further support the notion that sinus NOS is identical or very closely related to the type-2 NOS; however, the regulation of expression seems to be fundamentally different from that described previously for this NOS isoform.

Adult↗

Localization of nitric oxide synthase activity in the human lower urinary tract and its correlation with neuroeffector responses.

OBJECTIVES: The present study was designed to correlate the localization of nitric oxide synthase (NOS) activity to nerve-induced smooth muscle responses in the human lower urinary tract. METHODS: Nerve-induced smooth muscle activity was studied in the human lower urogenital tract. NOS activity was studied by measurement of citrulline formation and guanylate cyclase activity. RESULTS: Nerve-induced contractions in the human detrusor muscle, bladder neck, and prostatic urethra were not significantly enhanced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). In the prostatic urethra, relaxations to transmural nerve stimulation were obtained after increase in tension. The relaxations were abolished by L-NAME and restored by L-arginine. Nerve-induced relaxations were occasionally obtained in the bladder neck, whereas nerve-induced relaxations were never obtained in the detrusor muscle. Citrulline formation was highest in the prostatic urethra, it was intermediate in the bladder neck, and it was less pronounced in the detrusor muscle. Guanylate cyclase activity was also highest in the prostatic urethra, whereas there was no significant difference in guanylate cyclase activity in the bladder neck and detrusor muscle. CONCLUSIONS: The nerve-induced smooth muscle responses and the localization of NOS activity were in good agreement. Thus, in areas where marked relaxations to nerve stimulation were obtained, there was also a high NOS activity. The data suggest that nitric oxide is a mediator for the neurogenic dilation of the bladder neck and urethra during the micturition reflex.

Amino Acid Oxidoreductases↗

Nitrous oxide for colonoscopy discomfort: a randomized double-blind study.

The possibility of reducing recovery time after colonoscopy was studied using patient-administered nitrous oxide and comparing it with our standard treatment of ketobemidone plus midazolam. Fifty consecutive colonoscopy patients were randomized to receive either (i) intravenous ketobemidone hydrochloride 2.5 mg, midazolam 2.5 mg, and breathing air from a face mask with a demand valve (KHM) or (ii) intravenous saline and a breathing mixture of even parts of oxygen and nitrous oxide (Entonox) from the same valve setup. Patient discomfort during colonoscopy was assessed using visual analogue scales. All patients were allowed to stay for recovery as long as they wanted, and the time was measured. Modified recollection tests were performed prior to colonoscopy and when the patients left the Endoscopy Unit, in order to study the degree of mental impairment induced by the procedure and the medication. All patients had complete colonoscopies of the same duration in both groups. Discomfort during colonoscopy was rated the same in both groups (2p = 0.6413). Both groups of patients scored identically in the precolonoscopy recollection test. Most patients had a lower score after colonoscopy, but Entonox-treated patients scored significantly better than those with KHM (2p = 0.0250). Patients treated with Entonox opted to leave the Unit directly after the procedure (median 0 minutes; interquartile range 0-5 minutes) compared to 38 minutes for those with KHM (interquartile range 10-75 min), 2p < 0.001. It seems from our data that nitrous oxide gives pain relief equal to that in our standard treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Preoperative Intermaxillary Fixation has no Influence on Weight Loss Induced by Vertical Banded Gastroplasty.

Surgery is the only therapeutic modality that has shown lasting results in the treatment of morbid obesity. Ability to lose weight by voluntary dieting has been associated with unsatisfactory weight loss after gastroplasty. This report examines the effect of preoperative inter-maxillary fixation (IMF) on weight reduction induced by vertical banded gastroplasty (VBG). Twenty-four patients entered the study and were randomly assigned to either 10 weeks of IMF or 10 weeks on the waiting-list. Patient groups were similar in respect to age, gender and Body Mass Index (BMI). All patients were urged to lose weight preoperatively. Patients in the IMF group lost 18 kg (-12 to -36; median, range) and the waiting list group lost 3 kg (+ 3 to -30) during the 10 weeks prior to surgery. Total weight loss from time of inclusion to 24 months postoperatively was the same in both groups. Our results suggest that weight loss up to 2 years after VBG is not Influenced by short-term preoperative IMF. Although we found no obvious advantage in having patients pre-treated by IMF, our findings indicate that jaw wiring can be used for patients in whom moderate preoperative weight loss is desired without endangering the effect of VBG on body weight development.

Journal Article↗