Search PubMed⌕ Search

Biomedical subjects

L Backman

Publications and source records attributed to L Backman.

At least 55 records · Page 3Linked to original sources

Cloning, expression and characterization of two putative calcium-binding sites in human non-erythroid alpha-spectrin.

The C-terminus of alpha-spectrins contains two putative calcium-binding sites or EF-hands. To characterize the binding, we have isolated clones from a human fetal liver cDNA library and expressed several fragments comprising either one or both of these sites. When the isolated clones were sequenced, we found that three consecutive nucleotides differed compared to the published sequence. The discrepancy affected two codons in the first of the two putative calcium sites. These codons translated into glutamate and phenylalanine, which are identical to the residues present at the same position in other alpha-spectrins. In the presence of magnesium, only recombinant peptides comprising the second putative site bound calcium as determined by a calcium overlay assay. Although the first putative EF-hand appeared to bind some calcium in the absence of magnesium, no binding could be detected under stringent conditions. Therefore, it is likely that the second EF-hand constitutes the only functional calcium-binding site in the C-terminus of human non-erythroid alpha-spectrin. Since peptides comprising the second EF-hand bound calcium nearly as well as intact spectrin, it is also apparent that the second EF-hand constitutes the major binding site for calcium in spectrin. The relative change in negative ellipticity, induced by the binding of calcium, indicates a dissociation constant of approximately 120 microM.

Amino Acid Sequence↗

Increased liver carnitine content in obese women.

In experimental animals the enhancement of hepatic fatty acid oxidation and ketogenic capacity is accompanied by a rise in the concentration of liver carnitine. Massive obesity is characterized by enhanced fatty acid turnover, insulin resistance, and often a fatty liver. Carnitine concentrations were determined in liver, abdominal muscle tissue, and blood in morbidly obese women. The liver and muscle carnitine concentrations were significantly higher in the obese subjects than in the lean control subjects. These findings suggest an increase of the whole-body carnitine pool. In the obese subjects there was also a significant positive correlation between liver and muscle carnitine concentrations. In the majority of the obese subjects fatty changes could be demonstrated in the liver. The plasma insulin concentration tended to be positively correlated with the degree of fat infiltration and negatively correlated with the liver carnitine content. It is concluded that the liver carnitine content is significantly increased in obese women, which agrees with the finding in experimental animals.

Adult↗

Does the Size of the Upper Pouch Affect Weight Loss after Vertical Banded Gastroplasty.

BACKGROUND: The importance of creating a small 10-20 ml upper pouch when performing a vertical banded gastroplasty (VBG) is often stated in the literature. In order to test the hypothesis that weight loss is superior in patients with a small upper pouch, we examined the weight loss curves for three different pouch sizes in our patients operated with VBG. METHOD: Retrospective analysis of patients operated with VBG at our institution between November 1986 and April 1994 was done. A modified Mason VBG was performed with intraoperative balloon measurements of the size of the upper pouch. Three groups were identified according to different pouch volumes: 20 ml (n = 65), 30 ml (n = 46), and >/= 40 ml (n = 47). RESULTS: Of the 198 patients operated with VBG, pouch volume measurement was successful in 158 patients. Mean pouch volume was 32 ml at 50.5 cm of water. Loss of body mass index at 6, 12, 24, 48, 60 months did not significantly differ in the three groups. The rate of late reoperative procedures was also similar in the three groups. The incidence of staple-line breakdown (SLB) and endoscopically verified esophagitis was higher in the >/= 40 ml group. CONCLUSION: We have been unable to demonstrate a difference in weight loss after VBG for differing pouch volumes. There is an increased rate of SLB and esophagitis in the group with largest pouch volume; however, length of follow-up was longest for this group.

Journal Article↗

Characterization of the binding of calmodulin to non-erythroid spectrin.

Both brain and erythrocyte spectrin bound calmodulin in a calcium-dependent manner when immobilized on a polyvinylidene difluoride (PVDF) membrane, though the affinity of the non-erythroid spectrin was much greater than that of the erythroid isoform. The interaction was characterized further using equilibrium partition. In the presence of calcium, the partition behavior of calmodulin was affected by both spectrins, though brain spectrin caused a much larger change in partition. However, in both cases it was evident that the observed partition behavior of calmodulin was due to complex formation with spectrin. Analysis of the equilibrium partition data indicated the presence of a high-affinity site characterized by a dissociation constant of about 0.3 microM and probably one or more much weaker sites (> 0.3 mM). The presence of at least two distinct binding sites was substantiated by the observation that truncated recombinant spectrin fusion proteins comprising either the middle part or the C-terminal of non-erythroid alpha-spectrin bound calmodulin.

Animals↗

HLA compatibility and liver transplant outcome. Improved patient survival by HLA and cross-matching.

In liver transplantation (LTx), numerous studies have failed to demonstrate an adverse effect of HLA-A,B,DR incompatibility or of donor-specific positive cross-match on survival of the recipients. In this study, we examined the effect of antidonor cytotoxic antibody and HLA compatibility in 800 LTx recipients with CsA-based immunosuppression. Thirty-four of 482 (7%) recipients were transplanted across a positive donor-specific T cell cross-match. Four-year patient and graft survival was 71% and 67%, respectively, in negative cross-match recipients and 53% and 50%, respectively, in positive cross-match recipients (P = 0.0051 and P = 0.023). Neither B cell-positive cross-match nor the presence of panel reactive antibody (PRA) had an adverse impact on the liver allograft outcome. Interestingly, 21/58 (36.2%) patients with PRA > or = 10% had a positive T cell cross-match, whereas only 7/382 (1.8%) patients with PRA < 10% did (P < 0.0001). This indicates the predictive value of PRA cross-match results. B lymphocyte cross-match results also were strongly correlated with the presence of PRA, as 26/57 (45.6%) of the patients with PRA > or = 10% had a positive cross-match, whereas only 22/394 (5.6%) with PRA < 10% did (P < 0.0001). Analysis of HLA compatibility demonstrated a significant impact on patient's survival, comparing only 0-2 vs. 6 HLA-A+B+DR mismatches and 0 vs. 1 vs. 2 HLA-DR mismatches. Four-year patient survival rate for 0 to 2 antigen mismatches was 86%, whereas for 6 antigen mismatches it was 62% (P = 0.025). Overall actuarial 4-year patient survival rate in HLA-DR-mismatched groups (0 vs. 1 vs. 2) was 84%, 73%, and 64%, respectively (P = 0.033). In no mismatched category was graft survival rate significantly different. Sepsis or rejection was the cause of graft loss in 1/10 (10%), 21/75 (28%), and 34/85 (40%) patients with 0, 1, and 2 HLA-DR mismatches, respectively. The difference between patient and graft survival was accounted for by survival after retransplantation, which was lower in patients with more HLA-DR mismatches in primary transplants. The latter group received intensive immunosuppressive therapy during the first month after primary transplantation, as compared with those with fewer HLA-DR mismatches (P = 0.04). The above data suggest that prospective cross-match should be performed in patients with > or = 10% PRA if it is logistically feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Sodium selenite as modulator of red cell shape.

Addition of sodium selenite to human red cells, under ATP deplete conditions, induces a rapid oxidation of both glutathione and protein sulphydryl groups. Selenite also inhibits the discocyte-echinocyte shape transformation and stops the process before completion. Parallel to the effect on shape, selenite reduces the dephosphorylation of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate. Therefore our results support a shape change mechanism based on the metabolism of phosphoinositides and compatible with the bilayer-couple hypothesis.

Adenosine Triphosphate↗

Imaging human erythrocyte spectrin with atomic force microscopy.

Isolated spectrin covalently attached to a surface in a liquid environment as well as dried on mica has been studied with a contact-mode atomic force microscope. Both pyramidal and conical-type cantilever tip facets were used in the AFM. Our images show structures and give dimensions that correlate well with previous structural studies using transmission electron microscopy.

Erythrocyte Membrane↗

Marlex Mesh Gastric Banding: A 7-12 Year Follow-up.

This paper presents a 7-12 year (mean 9.8 years) follow-up of 92 extremely obese patients treated with Marlextrade mark mesh gastric banding (GB). The follow-up rate was 92% (85 patients). Weight loss was initially good (an average reduction in BMI of 13 during the first year), but late weight gain has been a common complaint and a reason for reoperation. Other complications that necessitated reoperation were severe vomiting and esophagus not amenable to medical treatment. Four patients have developed signs of Barrett's esophagus at late follow-up. Forty-six patients (50%) were reoperated 70 times for correction of the band or conversion to vertical banded gastroplasty (VBG). The most common reoperative procedure was conversion to VBG (38 patients). Only 25 (31%) of the 80 patients with long-term follow-up have an intact band. Our results show the need of long follow-up and that this GB cannot be recommended for the treatment of morbid obesity.

Journal Article↗

Hepatic esterification rate of cholesterol and biliary lipids in human obesity.

Obesity is often associated with an increased hepatic secretion rate of cholesterol and saturated gallbladder bile. In order to evaluate the role of hepatic esterification of cholesterol in this phenomenon, we assayed the activity of acyl CoA:cholesterol acyl transferase (ACAT), which catalyzes the esterification of cholesterol, in liver microsomes obtained from 19 morbidly obese patients without gallstones undergoing vertical banded gastroplasty. Gallbladder bile was obtained and analyzed for lipid composition, cholesterol saturation, nucleation time, and occurrence of cholesterol crystals. Fourteen non-obese gallstone-free subjects undergoing cholecystectomy because of suspected polyp or adenomyoma in the gallbladder served as controls. The hepatic content of esterified cholesterol was increased by about 70% in the obese patients (P < 0.05). Still, the mean levels of the ACAT activity were equal in the obese and non-obese patient groups (11 +/- 1 and 11 +/- 2 pmol/min per mg protein, respectively). When exogenous cholesterol was added to the assay system, the activity was increased markedly in both groups. The ACAT activity was higher in obese patients with steatosis of the liver compared with those displaying normal liver morphology (12 +/- 1 vs 8 +/- 1 pmol/min per mg, P < 0.05). Obese patients did not have significantly more saturated gallbladder bile than the non-obese controls (84 +/- 7 and 77 +/- 8%, respectively). They had a normal nucleation time and their gallbladder bile did not contain any cholesterol crystals. We conclude that obese patients without gallstones usually have a normal esterification rate of cholesterol in the liver. Steatosis of the liver was associated with increased ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lymphocyte and granulocyte function in nutritionally depleted patients. The effect of 2 weeks of total parenteral nutrition.

Parenteral nutrition has been reported to restore impaired immune function in nutritionally depleted patients. Lymphocyte and granulocyte function were studied before and after 2 weeks of total parenteral nutrition (TPN) in 9 depleted patients, 5 with gastrointestinal cancer and 4 with benign gastrointestinal disorders. The ability of purified blood lymphocytes to incorporate (14)C-labelled thymidine spontaneously and following mitogenic and antigenic stimulation was studied. Before TPN spontaneous lymphocyte activity was significantly increased and mitogen and antigen responsiveness significantly decreased in comparison to healthy controls. These abnormalities were more pronounced in patients with malignant disorders while the remaining patients showed a moderate impairment. No improvement in lymphocyte capacity was observed following 2 weeks of TPN. Granulocyte function measured as chemotaxis, phagocytosis, NBT-reduction and bactericidal capacity did not differ significantly between patients and controls and no changes were seen following nutritional treatment. These findings support the concept that the underlying disease and/or other factors rather than the secondary nutritional depletion are the main reasons for immune impairment. Furthermore, no immunomodulating effects of lipid emulsions on lymphocyte and granulocyte function, under these experimental conditions, were apparent.

Journal Article↗

Vertical Banded Gastroplasty: One Treatment for Esophagitis and/or Weight Gain after Gastric Banding.

Gastric banding (GB) was the method of choice for the surgical treatment of obesity at our institution between 1981 and 1986. We abandoned the method in 1986 because of poor results. Reflux esophagus and weight gain after a period of weight loss were common problems despite attempts at surgical correction. Of the 92 patients who underwent GB, 36 were reoperated with vertical banded gastroplasty (VBG) due to endoscopically verified esophagus, weight gain or both. Postoperatively, the patients reported ameliorated reflux symptoms without any substantial weight gain after the initial weight loss during the study period. The VBG, after GB, was performed with a rate of complications similar to that of primary VBG performed at our institution. Five patients (14%) were reoperated after the conversion with VBG, compared to 11% (15/134) and 55% (51/92) reoperated patients after primary VBG and GB respectively at our Institution. GB, by our technique, seems to be a poor procedure, and VBG is in comparison the method of choice.

Journal Article↗