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Biomedical subjects

J Johansson

Publications and source records attributed to J Johansson.

229 records · Page 13Linked to original sources

Influence of sex hormones on pancreatic cancer.

A possible new approach to treating pancreatic cancer has been suggested, since the presence of estrogen receptors, estrogen binding proteins, estramustin binding protein, and androgen receptors have been demonstrated in human pancreatic adenocarcinomas of ductular origin. Moreover, there is some evidence that there is a dysfunction of the hypothalamic-sex-organ axis, resulting in low values of gonadotropins as well as testosterone in serum. Confirmatory evidence that all these findings have therapeutic implications in humans is still lacking, but in experimental studies, inhibition as well as growth potentiation of pancreatic cancer can be demonstrated after hormonal manipulations.

Androgens↗

Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids.

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial overgrowth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial overgrowth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Anti-Ulcer Agents↗

Clinical outcome and long-term survival rates after esophagectomy are not determined by age over 70 years.

Esophagectomy is considered a high-risk procedure in patients aged 70 years or older. This study evaluates the impact of two age groups (younger than 70 and 70 years or older) on clinical outcome and long-term survival rates following this procedure. This prospective study included survival analysis and clinical evaluations at 3, 6, and 12 months after esophagectomy. All esophagectomy patients undergoing gastric (n = 125), jejunal (n = 10), or colonic (n = 4) reconstructions at our institution from 1984 to 1996 were included. Fifty patients were older than 70 years, 89 were younger, and 120 of these 139 patients had tumors. The overall hospital mortality rate was 1.4% (2 of 139), both in the younger age group. All leaks from anastomoses and grafts were nonfatal, and these problems occurred in seven patients in the younger age group and two in the older group. The mean preoperative weight was 70 kg, and there was a mean weight loss of 5 kg during the first three postoperative months only but none thereafter (P <0.001). This was the same for patients with benign and malignant disorders, and for those aged over or under 70 years. Between 71% and 77% of the patients experienced no dysphagia at the three evaluations during the first postoperative year. The distribution of the different grades of dysphagia was equal in the two age groups at 3-month (P = 0.339) and 12-month (P = 0.669) follow-up. The 12-year survival rate was 28% and the 5-year rate was 31%, and this was correlated to tumor stage (P = 0.002) but not to age over or under 70 years (P = 0.299). The clinical outcome was the same regardless of whether patients were over or under 70 years of age. Tumor stage but not age over 70 years was the major predictive factor for long-term survival.

Age Factors↗

Telomerase reverse transcriptase expression is increased early in the Barrett's metaplasia, dysplasia, adenocarcinoma sequence.

Barrett's esophagus is a multistage polyclonal disease that is associated with the development of adenocarcinoma of the esophagus and esophagogastric junction. Telomerase activation is associated with cellular immortality and carcinogenesis, and increased expression of the telomerase reverse transcriptase catalytic subunit (hTERT) has been used for the early detection of malignant diseases. To identify biomarkers associated with each stage of the Barrett's process, relative mRNA expression levels of hTERT were measured using a quantitative reverse transcription-polymerase chain reaction method (ABI 7700 Sequence Detector (TaqMan system) in Barrett's intestinal metaplasia (n = 14), Barrett's dysplasia (n = 10), Barrett's adenocarcinoma (n = 14), and matching normal squamous esophagus tissues (n = 32). hTERT expression was significantly increased at all stages of Barrett's esophagus, including the intestinal metaplasia stage, compared to normal tissues from patients without cancer (intestinal metaplasia vs. normal esophagus, P <0.0001; dysplasia, P = 0.001; adenocarcinoma, P = 0.007; all Mann-Whitney U test ). hTERT expression levels were significantly higher in adenocarcinoma tissues than in intestinal metaplasia tissues (P = 0.003), and were higher in dysplasia compared with intestinal metaplasia tissues (P = 0.056). hTERT levels were also significantly higher in histologically normal squamous esophagus tissues from cancer patients than in normal esophagus tissues from patients with no cancer (P = 0.013). Very high expression levels ([hTERT x 100: beta-actin] >20) were found only in patients with cancer. These findings suggest that telomerase activation is an important early event in the development of Barrett's esophagus and esophageal adenocarcinoma, that very high telomerase levels may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread cancer "field" effect is present in the esophagus of patients with Barrett's cancer.

Adenocarcinoma↗

Artificial surfactants based on analogues of SP-B and SP-C.

The hydrophobic proteins SP-B and SP-C are important components of natural surfactant preparations currently used in clinical practice, and physiologically active surfactants can be made from isolated SP-B and/or SP-C reconstituted with synthetic lipids. Efforts have been made to produce these polypeptides, or analogues with similarfunction, by organic synthesis or expression in heterologous systems. It is important to obtain proper folding of the synthetic peptides, as required for optimal interaction with the surfactant lipids. Another issue is to avoid loss of SP-C activity due to alpha-helix to beta-sheet transition. This latter problem can be circumvented by replacing the polyvaline stretch of SP-C with a polyleucine stretch containing a few lysines. Palmitoylation of cysteines or serines at positions 5 and 6 also seems important for the properties of SP-C. SP-B, which is too big a molecule to be easily produced by organic synthesis. apparently can be replaced in an artificial surfactant by a peptide capable of cross-linking phospholipid bilayers. The development of synthetic analogues of the surfacant proteins might make it possible to tailor artificial surfactants for specific therapeutic missions, for instance by enhancing resistance to inactivation by meconium, plasma proteins, or oxygen radicals or maximizing bacteriostatic effects.

Animals↗

High density lipoprotein particle size distribution in cord blood.

Cord blood from 73 full term healthy newborns and blood from adults were analysed for the protein content of high density lipoprotein subclasses separated by gradient gel electrophoresis. Cholesterol and triglyceride concentrations of very low (VLDL), low (LDL) and high (HDL) density lipoproteins were also analysed and newborns had lower concentrations of cholesterol and triglycerides in VLDL, LDL and HDL (p less than 0.001) than adults. The HDL3c subclass, comprising the smallest particles of the HDL particle spectrum, was the major component for newborns and the minor one for adults and was the only lipoprotein fraction with a higher concentration in cord than in adult blood. No sex differences were present for any of the lipoprotein levels of the newborns. Serum cholesterol concentrations were positively correlated to HDL2b (r = 0.49, p less than 0.001) and HDL2a levels (0.42, p less than 0.001), correlations confined to the cholesterol contents of HDL (r = 0.72 and r = 0.67 respectively, both p less than 0.001). Serum triglycerides were inversely correlated to HDL2b and HDL2a levels in male newborns only (r = 0.38 and r = 0.34 respectively, both p less than 0.05). Irrespective of sex, gestational age and birthweight the newborns had 2 typical HDL subclass distributions, characterized by high or low levels of HDL2b and HDL2a. The newborns with high HDL2b and HDL2a levels also had low VLDL lipid levels and high HDL cholesterol concentrations.

Adult↗

High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients.

The relations of high density lipoprotein (HDL) subclasses to severity and rate of progression of coronary atherosclerosis were investigated in 60 men who had survived a myocardial infarction before the age of 45 years and who had subsequently undergone two coronary angiographies, with an intervening time interval of 4-7 years between angiographies. Five HDL subclasses with different particle sizes were determined by gradient gel electrophoresis, and the major serum lipoprotein classes were separated by preparative ultracentrifugation in connection with the second angiography. Highly significant inverse correlations were found between the plasma levels of the largest HDL particles, the HDL2b subclass, and both disease severity as observed on the second coronary angiogram (r = -0.53, p less than 0.001) and progression of coronary lesions between angiographies (r = -0.38, p less than 0.01). Grouping the patients according to the presence or absence of very low density lipoprotein (VLDL) triglyceride elevation revealed striking differences in the relations of HDL subspecies to coronary atherosclerosis between normotriglyceridemic and hypertriglyceridemic subjects. There were strong inverse correlations between the plasma HDL2b concentration and both severity of lesions (r = -0.72, p less than 0.001) and rate of lesion progression (r = -0.58, p less than 0.01) in the normotriglyceridemic patients, whereas this relation was absent in subjects with hypertriglyceridemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Arthroscopic staple capsulorrhaphy for anterior shoulder instability.

We reviewed the results of the arthroscopic staple capsulorrhaphy on 47 patients with a followup of 4 years. Thirty-four of the 47 shoulders had a history of traumatic dislocation, while the remaining 13 had a history of subluxation. The recurrence rate was 25%, with 8 shoulders developing recurrent frank dislocation and 4 developing subluxation. Only 21 of the 47 patients were able to resume normal sporting activities after surgical repair. We had no cases of staple loosening within the joint, but we did have 3 patients whose staples were removed because of persistent pain in the shoulder.

Adolescent↗

[Determination of the amino acid spectrum as an aid in the up-dating of skeletal findings].

Estimation of the age of skeletal remains is usually based on subjective evaluation of the morphological grade of decomposition. This assumes, that the investigator is provided with pertinent experience. Experimentally elaborated physical and chemical methods proposed for objectification of the statements did not yet assest until today due to lacking temporal correlation. Our investigations were stimulated by observations on fossil bones indicating that the collagenbound amino acids diminish very slowly dependent on geological age. Samples of 53 skeletons of five to 2500 years were pulverized and subjected to acid hydrolysis. The amino acids released from bone collagen were separated by means of thin-layer chromatography and detected by isatin and ninhydrin reagents. The dye complexes of alanine, hydroxyproline, proline, tyrosine, and valine were measured densitometrically and quantified through calibration curves. We established, that the concentrations of the amino acids exhibited a time dependent reduction as equivalent of a loss collagen. The temporal correlation is very narrow (r less than -- 0,8) and sufficient for datings within plus/minus ten years of the more recent bones. Environmental conditions during post-mortem decay seem to have little influence on this process.

Alanine↗