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Biomedical subjects

L Sandberg

Publications and source records attributed to L Sandberg.

At least 19 recordsLinked to original sources
PubMed1999

A fast and simple method to calculate protonation states in proteins.

A simple model for electrostatic interactions in proteins, based on a distance and position dependent screening of the electrostatic potential, is presented. It is applied in conjunction with a Monte Carlo algorithm to calculate pK(alpha) values of ionizable groups in proteins. The purpose is to furnish a simple, fast, and sufficiently accurate model to be incorporated into molecular dynamic simulations. This will allow for dynamic protonation calculations and for coupling between changes in structure and protonation state during the simulation. The best method of calculating protonation states available today is based on solving the linearized Poisson-Boltzmann equation on a finite difference grid. However, this model consumes far too much computer time to be a practical alternative. Tests are reported for fixed structures on bacteriorhodopsin, lysozyme, myoglobin, and calbindin. The studies include comparisons with Poisson-Boltzmann calculations with dielectric constants 4 and 20 inside the protein, a model with uniform dielectric constant 80 and distance-dependent dielectric models. The accuracy is comparable to that of Poisson-Boltzmann calculations with dielectric constant 20, and it is considerably better than that with epsilon = 4. The time to calculate the protonation at one pH value is at least 100 times less than that of a Poisson-Boltzmann calculation. Proteins 1999;36:474-483.

Algorithms↗
PubMed1999

General expression vectors for production of hydrophobically tagged immunogens for direct iscom incorporation.

A new general strategy for the production of recombinant protein immunogens has been investigated. The rationale involves the production of a recombinant immunogen as fused to a composite tag comprising one domain suitable for affinity purification and a hydrophobic tag designed for direct incorporation through hydrophobic interaction of the affinity-purified immunogen into an adjuvant system, in this case immunostimulating complexes (iscoms). Three different hydrophobic tags were evaluated: (i) a tag denoted IW containing stretches of hydrophobic isoleucine (I) and tryptophan (W) residues; (ii) a tag denoted MI consisting of the transmembrane region of hemagglutinin from influenza A virus; and (iii) a tag denoted PD designed to be pH-dependent in such a way that an amphiphatic alpha-helix would be formed at low pH. As an affinity tag, an IgG-binding domain Z derived from Staphylococcus aureus protein A (SpA) was used, and a malaria peptide M5, derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, served as a model immunogen in this study. Three different fusion proteins, IW-Z-M5, MI-Z-M5 and PD-Z-M5, were produced in Escherichia coli, and after affinity purification these were evaluated in iscom-incorporation experiments. Two of the fusion proteins, IW-Z-M5 and MI-Z-M5 were found in the iscom fraction following preparative ultracentrifugation, indicating iscom incorporation. This was further supported by electron microscopy analysis showing that iscoms were formed. Furthermore, these iscom preparations were demonstrated to induce efficient M5-specific antibody responses upon immunization of mice, confirming successful incorporation into iscoms. The implications of these results for the design and production of subunit vaccines are discussed.

Amino Acid Sequence↗
PubMed1996

[Painless femoral neck fracture in a patient with multiple sclerosis].

We describe a patient with multiple sclerosis who suffered a painless hip fracture. She was admitted to the hospital three weeks after falling on her left hip. She had been unable to walk after the trauma, but had had no pain. The condition was initially misinterpreted as multiple sclerosis schub. X-ray examination showed fracture of the left femoral neck, and by the time she was admitted to hospital the patient was paretic. She has improved substantially after an operation involving cementless total hip arthroplasty. Painless fractures in patients with multiple sclerosis may be confused with exacerbations of their neurological disease.

Adult↗
PubMed1994

Increased serum levels of anti-elastin antibodies in patients with Peyronie's disease.

The cause of Peyronie's disease is unknown. Immunological mechanisms in the pathogenesis have been previously suggested. Antibodies to elastin are present in all individuals. However, abnormal serum levels of anti-tropoelastin (reflecting elastin synthesis) and anti-alpha-elastin (reflecting elastin destruction) are seen in a variety of autoimmune diseases. We show that patients with Peyronie's disease have higher levels of antibodies to tropoelastin (p < 0.047) and alpha-elastin (p < 0.012) than age-matched controls, suggesting an increase in elastin synthesis and breakdown, respectively. These findings suggest the presence of autoimmune mechanisms in the pathogenesis of Peyronie's disease, which may have future diagnostic and therapeutic implications.

Antibodies↗
PubMed1993

Abnormal immune function in malignant hypertension.

OBJECTIVE: To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension. DESIGN: Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies. METHODS: The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test. RESULTS: The frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration. CONCLUSION: The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.

Antibody Formation↗
PubMed1987

"Panic disorder" in schizophrenia.

A patient is described with operationally diagnosed chronic schizophrenia who simultaneously experienced repeated "attacks" during which times he had intense apprehension and autonomic hyperactivity entirely similar to that usually described under the rubric of "panic attacks" in nonschizophrenic patients. Delusional and hallucinatory symptoms were also transiently exacerbated during these episodes. Alprazolam, as an adjunct to fluphenazine decanoate, was effective in ameliorating these symptoms. Diagnostic and treatment implications are discussed.

Adult↗
PubMed1986

Effect of heparin and heparin fractions on experimental abscess formation.

To evaluate the effectiveness of heparin and heparin fractions in decreasing abscess formation, rats were divided into six groups. A fibrin clot containing 10(9) live Escherichia coli was placed in the peritoneal cavity of each rat. Group 1 (controls) received daily subcutaneous (SQ) injections of 0.1 mL of saline solution. Group 2 received daily intramuscular injections of gentamicin, 12.5 mg/kg. Group 3 received a daily SQ dose of 30 U of porcine heparin. In addition to gentamicin, group 4 received heparin, group 5 received heparin fraction PK10169, and group 6 received heparin fraction CY216, all in daily SQ doses of 30 U. Survivors were killed at ten days and examined for intra-abdominal abscesses. All group 1 animals developed abscesses. Abscess formation was significantly decreased in all groups receiving gentamicin. When used with gentamicin, neither heparin nor heparin fractions decreased the number of abscesses formed when compared with gentamicin alone. Heparin or heparin fractions in combination with gentamicin did decrease abscess size significantly when compared with controls.

Abscess↗
PubMed1986

Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome.

A long-acting somatostatin analog, SMS 201-995, is now available to treat the hormonal manifestations of islet cell tumors. We report its use in a patient with a metastatic glucagonoma refractory to conventional therapy. This patient, who was severely disabled by the rash of necrolytic migratory erythema and brittle diabetes mellitus, allowed us to evaluate the therapeutic efficacy of SMS 201-995 and to gain insight into the origin of the rash. SMS 201-995 was administered subcutaneously (.05 mg twice a day). The rash improved markedly within 48 hours and was completely resolved within 1 week of treatment. Insulin requirements decreased from 90 U/day to zero during the first week of treatment. Corresponding to improvement in clinical symptoms circulating glucagon levels showed a marked decrease. There was no substantial change in plasma or urinary levels of zinc or in plasma amino acid levels. When SMS 201-995 was stopped, the rash recurred within 36 hours and it improved within 48 hours of readministration. The rash and diabetes have remained well controlled during 8 months of therapy but no change in tumor size has been seen on CT scan. The rapid changes in the rash related to the administration of SMS 201-995 indicate that the pathogenesis of necrolytic migratory erythema is probably due to circulating hyperglucagonemia or some other hormonal substance produced by the tumor.

Adenoma, Islet Cell↗