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Biomedical subjects

J Johansson

Publications and source records attributed to J Johansson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Interaction of the antidepressant mirtazapine with alpha2-adrenoceptors modulating the release of 5-HT in different rat brain regions in vivo.

Mirtazapine (MIR) is a novel antidepressant, reported to raise extracellular noradrenaline (NA) through blockade of alpha2-autoreceptors and serotonin (5-HT) output via (1) indirect activation of facilitatory alpha1-adrenoceptors on the cell bodies of ascending 5-HT neurones and (2) blockade of presynaptic release-modulating alpha2-heteroreceptors on 5-HT terminals in the forebrain. To further assess the effect of MIR on NA/5-HT system interplay, including putative regional differences in the effects of the drug on 5-HT release in rat forebrain, we used in vivo microdialysis in anaesthetised rats. Probes were implanted in the dorsal hippocampus (DH) and frontal cortex (FCx), representing median and dorsal raphe 5-HT projection areas, respectively. In the DH, MIR (10 mg/kg s.c.) completely blocked the 5-HT release-suppressing action of the selective alpha2-adrenoceptor agonist clonidine (0.1 mg/kg s.c.), but had no effect per se on the 5-HT output. Neither drug significantly changed the 5-HT levels in the FCx. MIR perfused locally (10 microM via reverse-dialysis) also failed to significantly elevate 5-HT output, and did not affect the clonidine response in either brain area. Thus, the data confirm the basic alpha2-adrenoceptor-blocking properties of MIR, but are only partly concordant with previous studies reporting an increase of 5-HT output after MIR alone. Moreover, we find no elevation in 5-HT by the reference alpha2-adrenoceptor antagonist idazoxan (0.3-1.0 mg/kg s.c.). The discrepancies encountered, and the potential ability of alpha2-adrenoceptor antagonists in general to raise the output of 5-HT, are discussed with particular reference to methodological and other factors that may influence the experimental outcome (e.g., brain regional aspects, different alpha2-adrenoceptor subtypes, potential differences in adrenoceptor tone under varying experimental conditions).

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2000

Anastomotic diameters and strictures following esophagectomy and total gastrectomy in 256 patients.

The prevalence of anastomotic strictures in esophageal anastomoses provides us with limited information about the anastomotic healing process. This prospective study evaluates the exact esophageal anastomotic diameters in 256 patients who underwent esophagectomy and esophagogastrostomy without pyloroplasty (n = 107) or total gastrectomy and Roux reconstruction (n = 149). No perioperative chemoradiotherapy was given. Anastomotic strictures and diameters were assessed during endoscopy by a separately inserted (inflated to the anastomotic width) balloon catheter. The anastomotic diameters increased significantly during the first postoperative year in the esophagectomy (p = 0.001) and gastrectomy (p < 0.001) groups. The anastomoses in the gastrectomy group were significantly wider than those in the esophagectomy group 3 (25.7 versus 19.9 mm), 6 (28.5 versus 22.0 mm), and 12 (30.5 versus 23.3 mm) months after surgery (p < 0.001). Neither the anastomotic site (neck or chest) in the esophagectomy group (p = 0.176) nor that in the gastrectomy group (abdomen or chest) (p = 0.577) influenced the anastomotic diameter. Benign anastomotic strictures were most frequently found after 3 months and after esophagectomy. Esophagojejunostomies performed with 2 linear stapling devices or cartridge size 28 mm showed the widest anastomoses with only 1 stricture. Esophagogastric anastomoses following esophagectomy are narrower and develop more strictures than esophagojejunal anastomoses after total gastrectomy, but both dilate during the first year.

Adult↗
PubMed2000

Synthetic surfactants to treat neonatal lung disease.

Pulmonary surfactant is a complex of surface-active lipids mixed with specific proteins. Two of these, SP-B and SP-C, are essential for adsorption of surfactant lipids to the air-liquid interfaces of the lungs and, hence, are also essential for alveolar stability and effective gas exchange. Surfactant substitutes must contain at least one of these proteins (or analogues of them) to be optimally effective when administered into the airways of babies with surfactant deficiency or dysfunction. This review describes how an increased understanding of the properties of surfactant proteins has led to the development of improved synthetic surfactants with the potential to treat a wide range of respiratory disorders.

Amino Acid Sequence↗
PubMed2000

Cytogenetic findings in a population-based series of 787 childhood acute lymphoblastic leukemias from the Nordic countries. The NOPHO Leukemia Cytogenetic Study Group.

Different types of leukemia are characterized by different patterns of nonrandom chromosomal aberrations, but the frequencies with which the various karyotypic subtypes are seen differ among cytogenetic laboratories, countries, and geographic regions. During the 12-yr period 1986-1997, a total of 2054 children (< 15 yr of age) were diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden). Cytogenetic analyses were successfully performed in 1372 patients, 787 (57%) of whom displayed clonal chromosomal abnormalities. ALL with > or = 47 chromosomes was the most frequent cytogenetic subgroup (63%), with massive hyperdiploidy (> or = 52 chromosomes) and chromosome numbers in the tri- and tetraploid range, constituting 46% of all abnormal cases. ALL-associated translocations were found at low frequencies [11q23 translocations in 3.7%, t(9;22)(q34;q11) or del(22q) in 2.2%, t(4; 11)(q21;q23) in 2.0%, t(11;19)(q23;p13) in 1.40%, t(1;19)(q23;p13) in 1.3%, and t(8;14)(q24;q32) in 1%]. Two rearrangements not previously reported in childhood ALL, but recurrent in this population-based material, were identified: der(7;9)(q10;q10) and t(9;12)(q22;p11-12), the molecular genetic consequences of which are unknown. Hyperdiploid childhood leukemias, especially those with a high hyperdiploid modal number, thus seem to be more frequent and ALL-specific translocations less frequent in the Nordic countries than in other geographic regions. Although technical differences among laboratories cannot be ruled out as a cause of at least some of the frequency differences observed compared with previous studies, systematic differences in exposure to environmental oncogenic factors or in geographic/ethnic origin are an intriguing possibility.

Adolescent↗
PubMed2000

Neither low-calorie diet nor vertical banded gastroplasty influence gastro-oesophageal reflux in morbidly obese patients.

OBJECTIVE: Investigate the effect of a liquid diet, and of vertical banded gastroplasty, on gastro-oesophageal reflux in morbidly obese patients. DESIGN: Prospective study, patients being their own controls. SETTING: University hospital, Sweden. SUBJECTS: 25 morbidly obese patients, listed for vertical banded gastroplasty. INTERVENTIONS: 24 hour ambulatory intra-oesophageal pH-monitoring three weeks before operation and repeated after 10-14 days on a liquid very low calorie diet, and finally three weeks after operation, while still on a liquid very low calorie diet. MAIN OUTCOME MEASURES: Percentage of time that pH in the oesophagus was < or =4. RESULTS: There were no changes in the amount of reflux, either after a liquid diet or after vertical banded gastroplasty. CONCLUSIONS: Neither the liquid diet nor vertical banded gastroplasty alone had any appreciable effect on gastro-oesophageal reflux.

Adult↗
PubMed2000

Hereditary vascular dementia linked to notch 3 mutations. CADASIL in British families.

The most common form of familial vascular dementia is considered to be CADASIL or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, which is now also increasingly manifest in the United Kingdom. CADASIL has been previously dubbed as a familial form of Binswanger disease. However, unlike in Binswanger disease CADASIL does not involve hypertension or other risk factors associated with cardiovascular disease. CADASIL appears to be essentially a disorder of the arteries that is linked to single missense mutations in the NOTCH 3 gene locus on chromosome 19. The pathogenesis of the disorder or the genetic mechanism leading to brain infarcts and dementia is not known. The elucidation of the microvascular pathology evident in CADASIL may be an interesting way to delineate effects of defective genes on brain cells from systemic vascular influences.

Cardiovascular Diseases↗
PubMed2000

Role of C-peptide in human physiology.

The C-peptide of proinsulin is important for the biosynthesis of insulin but has for a long time been considered to be biologically inert. Data now indicate that C-peptide in the nanomolar concentration range binds specifically to cell surfaces, probably to a G protein-coupled surface receptor, with subsequent activation of Ca(2+)-dependent intracellular signaling pathways. The association rate constant, K(ass), for C-peptide binding to endothelial cells, renal tubular cells, and fibroblasts is approximately 3. 10(9) M(-1). The binding is stereospecific, and no cross-reaction is seen with insulin, proinsulin, insulin growth factors I and II, or neuropeptide Y. C-peptide stimulates Na(+)-K(+)-ATPase and endothelial nitric oxide synthase activities. Data also indicate that C-peptide administration is accompanied by augmented blood flow in skeletal muscle and skin, diminished glomerular hyperfiltration, reduced urinary albumin excretion, and improved nerve function, all in patients with type 1 diabetes who lack C-peptide, but not in healthy subjects. The possibility exists that C-peptide replacement, together with insulin administration, may prevent the development or retard the progression of long-term complications in type 1 diabetes.

Amino Acid Sequence↗
PubMed2000

Screening for oesophageal adenocarcinoma: an evaluation of a surveillance program for columnar metaplasia of the oesophagus.

BACKGROUND: Screening patients with columnar metaplasia of the oesophagus for adenocarcinoma is controversial owing to the low cancer incidence and diverging opinions as to whether screening improves the prognosis of these patients. Our aim was to evaluate a screening program for adenocarcinoma in patients with columnar metaplasia in the oesophagus, with focus on cancer incidence and costs. METHODS: One hundred and ninety-nine patients with columnar metaplasia of the oesophagus were identified through an endoscopy database, and the original patient records were reviewed. RESULTS: The patients were followed up for 797 years in total and during this time were subjected to 1071 upper gastrointestinal endoscopies. During the screening period 5 patients presented with adenocarcinoma; thus the cancer-incidence was 1 in 159 patient-years. The cost of detecting one cancer was 294,950 SEK (US$ 37,815). However, only four of the five patients were suitable for oesophagectomy, and of these, one patient turned out to have an advanced cancer. All patients developing cancer had columnar metaplasia of the oesophagus longer than 3 cm and specialized columnar epithelium (intestinal metaplasia/Barrett oesophagus). CONCLUSIONS: Low cancer incidence, high costs, and the doubtful prognosis for the patients with identified cancer question the benefits and cost-effectiveness of cancer screening among patients with columnar metaplasia in the oesophagus.

Adenocarcinoma↗
PubMed2000

Prospects for a new synthetic surfactant.

Physiologically active artificial surfactants can be made from lipids and analogs of SP-C and SP-B, the latter serving as cross-linking peptides promoting the formation of a surface-associated surfactant reservoir. Artificial surfactants can probably be tailored to maximize resistance to inactivation by meconium and plasma proteins by modifying the amino acid sequence of the protein analogs or adding non-ionic polymers to the final product. Comparative clinical trials are required to evaluate the efficacy of these new artificial surfactants in various forms of neonatal lung disease.

Animals↗
PubMed1999

Amyloid fibril formation by pulmonary surfactant protein C.

Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric alpha-helix into beta-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.

Adolescent↗
PubMed1999

A method for S- and O-palmitoylation of peptides: synthesis of pulmonary surfactant protein-C models.

A method for O- and S-palmitoylation of non-protected peptides has been developed. The peptides are treated with excess of palmitoyl chloride in 100% trifluoroacetic acid for 10 min at room temperature. The acidic conditions prevent acylation of amino groups, which is only significant after prolonged treatment (hours to days). The tripeptides Gly-Cys-Phe and Gly-Ser-Phe were converted into the respective S- and O-palmitoylated compounds, and the hydrophobic pulmonary surfactant protein-C model peptides, LRIPCCPVNLKRLLVVV [SP-C(1-17)] and FGIPSSPVLKRLLILLLLLLLILLLILGALLMGL [SP-C(Leu)] were converted into their respective S,S- and O,O-dipalmitoylated peptides. The reactions were virtually quantitative, and the palmitoylated peptides were isolated in about 75-80% yield after reversed-phase HPLC purification. CD spectroscopy showed that S, S-dipalmitoylation of SP-C(1-17) affects the peptide secondary structure (substantial increase in the alpha-helix content) in dodecylphosphocholine micelles.

Amino Acid Sequence↗
PubMed1999

Porcine pulmonary surfactant preparations contain the antibacterial peptide prophenin and a C-terminal 18-residue fragment thereof.

Surfactant preparations obtained from porcine lungs by extraction with chloroform/methanol followed by chromatography over Lipidex-5000 are used for treatment of respiratory distress syndrome in preterm infants. These preparations contain about 98% phospholipids and 1-2% of the hydrophobic pulmonary surfactant-associated proteins B and C (SP-B and SP-C). Separation of the proteins in the surfactant preparation by reversed-phase high performance liquid chromatography revealed, in addition to SP-B and SP-C, the presence of three peptides derived from the cathelicidin family of antibacterial peptides. The 79-residue proline-rich peptide prophenin (identical to that isolated from leukocytes), an 80-residue prophenin with an N-terminal pyroglutamic acid residue, and a C-terminal 18-residue fragment of prophenin were found in approximate molar ratios of 1:20:5. A synthetic version of the C-terminal 18-residue peptide exhibits salt-dependent antibacterial activity (higher activity in the absence of salt) against the Gram-positive bacterium Bacillus megaterium Bm11 and, to a lesser extent, against Gram-negative Escherichia coli D21 cells. It appears possible that the presence of prophenin peptides may contribute to the antibacterial properties of surfactant preparations.

Amino Acid Sequence↗
PubMed1999

Differential protease-mediated turnover of H-NS and StpA revealed by a mutation altering protein stability and stationary-phase survival of Escherichia coli.

The Escherichia coli proteins H-NS is recognized as an important component among the major nucleoid-associated proteins. In studies of E. coli strains with defects in H-NS, we discovered a mutant that phenotypically restored stationary-phase viability (Rsv) of such strains. The Rsv phenotype was the result of a mutation that led to severalfold higher levels of the functionally and structurally related StpA protein. This mutation was a base pair change in the stpA structural gene, and the amino acid substitution in the StpA protein altered its turnover properties, suggesting a role for this residue in a cleavage site for proteolysis. We determined the stability of the StpA and the H-NS proteins and found that the StpA protein was degraded relatively rapidly in strains lacking functional H-NS, whereas H-NS remained stable irrespective of the presence/absence of StpA. Using protease-deficient mutants, we obtained evidence that the Lon protease was responsible for the degradation of StpA. The differential turnover of the nucleoid-associated proteins is suggested to contribute to the regulation of their stoichiometry and ratio in terms of homo- and heteromer formation. We conclude that StpA, in contrast to H-NS, is present mainly in heteromeric form in E. coli.

ATP-Dependent Proteases↗
PubMed1999

Biophysical activity of an artificial surfactant containing an analogue of surfactant protein (SP)-C and native SP-B.

Natural surfactant preparations containing phospholipids and the hydrophobic surfactant proteins B and C (SP-B and SP-C) are effective in the treatment of respiratory distress syndrome in premature infants. The limited supply, and the risk of infectious agents and immunological reactions have promoted the evaluation of synthetic peptides in surfactant preparations. However, the folding of synthetic SP-C into an alpha-helix is inefficient and alpha-helical SP-C analogues with Val-->Leu substitutions form oligomers. In order to circumvent these problems we have synthesized an SP-C analogue, named SP-C(LKS), which differs from SP-C mainly by the exchange of most of the Val residues in positions 16-28 with Leu residues to promote an alpha-helical conformation, and by the introduction of Lys residues at positions 17, 22 and 27 in order to locate positive charges around the helical circumference and thereby avoid self polymerization. CD spectroscopy showed a spectrum typical for alpha-helical peptides and SDS/PAGE disclosed a single band. The biophysical activity of artificial surfactant preparations containing SP-C(LKS) and phospholipids, with and without native SP-B, was measured using a Wilhelmy balance and a pulsating bubble surfactometer. SP-C(LKS) (3%, w/w) in a mixture of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol/palmitic acid (68:22:9, by wt.) suspended in 150 mM NaCl, showed rapid spreading at the air-liquid interface and produced a surface tension of <1 mN/m at minimum bubble size (gammamin) and 42 mN/m at maximum bubble size (gammamax) in the pulsating bubble surfactometer. The addition of 2% (w/w) SP-B to the preparation reduced the maximum surface tension to 33-35 mN/m, i.e. both gammamin and gammamax values were similar to those of natural surfactant preparations. Optimal in vitro characteristics were also obtained from a preparation containing SP-C(LKS), SP-B, DPPC and phosphatidylglycerol, i.e. when palmitic acid was omitted from the lipid mixture. SP-B containing surfactant preparations made up in Hepes buffer at pH 6.9, instead of in 150 mM NaCl, had similar biophysical activity provided that palmitic acid was omitted, but decreased activity in the presence of palmitic acid.

Amino Acid Sequence↗
PubMed1999

[Growing genes cause neurological diseases].

A growing number of hereditary neurodegenerative disorders have been found to be caused by expansion of trinucleotide repeats. A smaller number of diseases such as fragile X syndrome, myotonic dystrophy, and Friedreich's ataxia, have been found to be due to expansions in non-coding DNA. In a large group of diseases, the expansion consists of CAG repeats in the coding region of the gene, producing an expanded polyglutamine sequence in the protein. Nine diseases have so far been identified as belonging to this group: Huntington's disease, spinobulbar muscular atrophy (SBMA), dentatorubral pallidoluysian atrophy (DRPLA), autosomal dominant "pure" spastic paraplegia (ADPSP), and five forms of spinocerebellar ataxia (SCA 1,2,3,6 and 7). Except for SBMA, all of the CAG repeat disorders are characterised by autosomal dominant heredity and anticipation (i.e., earlier onset age and increasing severity in successive generations). The mutated protein causes disease via an as yet unidentified gain-of-function mechanism in specific subsets of neurones. Today, DNA analysis permits the diagnosis of a trinucleotide disease in individual cases.

Anticipation, Genetic↗
PubMed1999

Endoscopic grading of the gastroesophageal valve in patients with symptoms of gastroesophageal reflux disease (GERD).

BACKGROUND: It has been suggested that endoscopic grading of the gastroesophageal flap valve is a good predictor of the reflux status. METHODS: To test this hypothesis, 268 symptomatic patients underwent endoscopic grading of the gastroesophageal valve using Hill's classification, with grades I through IV. Esophageal acid exposure, lower esophageal sphincter characteristics, and the degree of esophageal mucosal injury were compared among the groups. RESULTS: The prevalence of a mechanically defective sphincter, abnormal esophageal acid exposure, erosive esophagitis, and Barrett's esophagus increased with increasing alteration of the gastroesophageal valve. The presence of a grade IV valve indicated increased esophageal acid exposure in 75% of patients. As a predictor, this is similar to lower esophageal sphincter pressure but not as good as the presence of esophageal mucosal injury. CONCLUSIONS: Endoscopic grading of the gastroesophageal valve provides useful information about the reflux status but is less useful as an indicator of gastroesophageal reflux disease (GERD) than the presence of esophageal mucosal injury.

Adolescent↗
PubMed1999

Pharyngeal reflux after gastric pull-up esophagectomy with neck and chest anastomoses.

OBJECTIVE: Pharyngeal reflux after a gastric pull-up esophagectomy may cause aspiration. This study evaluates acid exposure to the esophageal remnant and to the pharynx after gastric pull-up esophagectomy and evaluates the impact of additional dissection of the esophagus that is necessary for neck anastomoses versus no neck exploration and proximal chest anastomoses. METHODS: Forty-seven patients had circular stapled anastomoses in the apex of the right chest (n = 27 patients) or manually sutured neck anastomoses (n = 20 patients). A 24-hour double-pH study with the probes placed 3 cm cranial and 3 cm distal to the cricopharyngeal muscle was performed. The percent time pH less than 4 was registered 3, 6, and 12 months after the operation. RESULTS: Mean acid exposure to the proximal pH probe ranged between 0.2% and 0.96% and between 1.45% and 6.5% to the distal pH probe during the 3 measurements. Acid exposure was always lower to the proximal than to the distal probe (P =.001). Patients with neck anastomoses had increasing acid exposure to the distal (P =.023) and proximal (P =.002) pH probes during the study year, whereas patients with chest anastomoses had similar acid exposure. CONCLUSIONS: Acid exposure to the esophageal remnant and to the pharynx increased during the first postoperative year in patients with neck anastomoses but not in patients with proximal chest anastomoses. The results suggest a less favorable acid clearance in patients with the neck approach.

Anastomosis, Surgical↗