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Biomedical subjects

C Andersson

Publications and source records attributed to C Andersson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX.

The cellular basis of cystic fibrosis (CF) is a defect in a cyclic adenosine monophosphate (cAMP)-activated chloride channel (CF transmembrane conductance regulator) in epithelial cells that leads to decreased chloride ion transport and impaired water transport across the cell membrane. This study investigated whether it was possible to activate the defective chloride channel in cystic fibrosis respiratory epithelial cells with 4-phenylbutyrate (4PBA), genistein and 8-cyclopentyl-1,3-dipropylxanthine (CPX). The CF bronchial epithelial cell line CFBE41o-, which expresses the deltaF508 mutation, was treated with these agents and loss of Cl-, indicating Cl- efflux, measured by X-ray microanalysis. 8-bromo-cAMP alone did not induce Cl- efflux in CFBE41o- cells, but after incubation with 4PBA a significant efflux of Cl- occurred. Stimulation of cells with a combination of genistein and cAMP also induced Cl- efflux, whereas a combination of pretreatment with 4PBA and a combined stimulation with genistein and cAMP induced an even larger Cl- efflux. Cl- efflux could also be stimulated by CPX, but this effect was not enhanced by 4PBA pretreatment. The deltaF508 mutation leads to impaired processing of the cystic fibrosis transmembrane conductance regulator. The increased efflux of chloride after 4-phenylbutyrate treatment can be explained by the fact that 4-phenylbutyrate allows the deltaF508 cystic fibrosis transmembrane conductance regulator to escape degradation and to be transported to the cell surface. Genistein and 8-cyclopentyl-1,3-dipropylxanthine act by stimulating chloride ion efflux by increasing the probability of the cystic fibrosis transmembrane conductance regulator being open. The combination of 4-phenylbutyrate and genistein may be useful in a potential pharmacological therapy for cystic fibrosis patients with the deltaF508 mutation.

Cell Line↗
PubMed2000

Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria.

OBJECTIVE: To assess signs of distal neuropathy in patients with acute intermittent porphyria (AIP). DESIGN: A population-based study. SUBJECTS: All patients with DNA-verified AIP >/= 18 years of age in the four most northerly counties of Sweden. INTERVENTION: Validated neuropathic signs and tests such as monofilament test, neuropathic pain, dry feet, extensor digitorum brevis (EDB) test, loss of forefoot arch, hammer toes and ulceration. RESULTS: A total of 356 patients were registered and 339 of them (95%) participated in the neuropathy study. The chronic neurological signs were symmetrical and similar to those in type 1 diabetic patients. Significant impairment was found concerning perception, EDB test, lower leg pain, ankle and knee tendon reflexes, but not concerning dry feet, loss of forefoot arch and hammer toes, on comparing patients with manifest versus latent AIP. The neurological signs were more severe in the diabetic patients (n = 298). Five AIP patients had permanent quadriplegia after severe attacks. CONCLUSIONS: Patients with manifest AIP had significantly more signs of distal chronic, symmetrical neuropathy of axonal type than did patients with latent AIP. More grave neurological lesions appear to develop after severe attacks.

Adolescent↗
PubMed2000

Renal symptomatology in patients with acute intermittent porphyria. A population-based study.

OBJECTIVE: Can renal insufficiency in subjects with acute intermittent porphyria (AIP) be due solely to DESIGN: A population-based study. SUBJECTS: Subjects with AIP > or = 18 years of age (n = 386) in the four most northerly counties of Sweden. INTERVENTIONS: Screening with creatinine clearance at 24 h. Patients below the lower reference level underwent a repeat clearance test and, if still low, also chromEDTA clearance. RESULTS: 286 (74%) subjects performed the creatinine clearance test and in 57 clearance was low; the second clearance proved normal in 23 who were then excluded. Eighteen subjects with other possible medical reasons for renal insufficiency, ethical reasons or refusing further examinations were also excluded. The 16 remaining subjects with no explanation for their renal insufficiency other than AIP were then studied in detail. All 14 women, mean age 52 years, and two uraemic men, 58 and 67 years, had manifest AIP. Twelve patients had hypertension (HT) and four were normotensive in spite of renal insufficiency. Histological findings of renal biopsies revealed diffuse glomerulosclerotic and interstitial changes with additional ischaemic lesions. CONCLUSION: Protracted vasospasm in attacks of AIP may be a cause of renal lesions. This is discussed.

Adolescent↗
PubMed2000

The W198X and R173W mutations in the porphobilinogen deaminase gene in acute intermittent porphyria have higher clinical penetrance than R167W. A population-based study.

In northern Sweden, 468 patients with DNA-verified acute intermittent porphyria (AIP) were registered. A higher prevalence of manifest AIP was found in patients with mutations W198X and R173W when separately compared with mutation R167W, indicating higher clinical penetrance. Signs of increased seriousness of the disease were also found in patients with the W198X and R173W mutations in relation to the number and duration of attacks, impaired renal function and chronic disability. One explanation could be lower PBGD enzyme activity resulting from the W198X and R173W mutations than from the R167W mutation, though other factors might also be the cause.

Female↗
PubMed2000

Protection against respiratory syncytial virus (RSV) elicited in mice by plasmid DNA immunisation encoding a secreted RSV G protein-derived antigen.

Plasmid vectors encoding two different variants, one cytoplasmic and one secreted version, of a candidate vaccine BBG2Na to respiratory syncytial virus (RSV), were constructed and evaluated in a nucleic acid vaccination study. The two different vectors, which employed the Semliki Forest virus gene amplification system, were found to express BBG2Na appropriately in in vitro cell cultures. Immunisation of mice with the plasmid vectors elicited significant serum anti-BBG2Na IgG responses only in the mice receiving the plasmid encoding the secreted version of BBG2Na. Consistent with antibody induction data, sterilising lung protection against RSV-A challenge was also only observed in this group. These results indicate that the targeting of antigen expression (intracellular versus secreted) would be an important factor to consider in the design of nucleic acid vaccines.

Animals↗
PubMed1999

[Big differences in leadership and management training within health care services. Leadership and issues concerning cooperation should be more emphasized in basic medical education].

A recent survey of medical management programmes at universities across the country showed manifest national differences to exist, both quantitative and qualitative. Using a questionnaire, the Swedish Society of Medical Management examined the programmes for physiotherapists, occupational therapists, social workers, nurses and physicians, with respect to such issues as leadership, self-awareness and communication, health economics, and administration. It was concluded that knowledge acquired differs between fields; that physiotherapy programmes tend to have a very didactic approach; that nurses are taught the importance of participation in developmental processes; that doctors are exposed to somewhat the same approach but to a large extent on a voluntary basis; and that social workers obtain good insight into the administrative skills necessary to their work. In the article it is concluded that students would benefit from orientation in the diverse approaches used in the other fields than their own, and that pooling of resources among different programmes might be a more economic alternative to current practice.

Communication↗
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↗
PubMed1999

The mean hydration of carbohydrates as studied by normalized two-dimensional radial pair distributions.

The hydration of carbohydrates plays a key role in many biological processes. Molecular dynamics simulations provide an effective tool for investigating the hydration of complex solutes such as carbohydrates. In this article we devise an algorithm for the calculation of two-dimensional radial pair distributions describing the probability of finding a water molecule in a site defined by two reference atoms. The normalized 2D radial pair distribution is proposed as an effective tool for investigating and comparing localized or ordered water sites around flexible molecules such as carbohydrates when analyzing molecular dynamics simulations and the utility of 2D radial pair distributions is demonstrated using sucrose as an example. In this relatively simple structure, 2D radial pair distributions were able to characterize and quantify the importance of two unique interresidue hydration sites in which a water molecule is forming a bridge between the glycopyranosyl and fructofuranosyl residues. The approach is proposed to be a valuable tool for comparing and understanding the hydration of flexible biomolecules such as carbohydrates.

Algorithms↗
PubMed1999

Effects of diabetes mellitus on patients with acute intermittent porphyria.

OBJECTIVES: To study the effects of diabetes mellitus in patients with acute intermittent porphyria (AIP). Haeme deficiency in the liver of AIP patients stimulates an increase in ALA-synthase which triggers an escalating metabolic chain reaction, leading to an increase in the porphyrin content. This reaction can be reduced by treating AIP patients with haeme arginate or with glucose. DESIGN: A population-based study of all patients > 18 years of age having DNA-verified AIP (n = 328) living in the two most northerly counties of Sweden (Norrbotten and Västerbotten, with 550,000 inhabitants) of whom 16 had type 2 diabetes. Prevalence of diabetes was studied retrospectively in 26 AIP patients with hepatocellular carcinoma (HCC). RESULTS: None of the patients showed symptoms of AIP after the onset of their diabetes. Three patients had had recurrent, severe attacks for many years but when their diabetes became manifest, their urinary ALA and PBG levels decreased and the AIP symptoms resolved, to the relief of the patients. Amongst the 26 AIP patients with HCC, only one with signs of diabetes was identified (impaired glucose tolerance test). CONCLUSIONS: This study raises the possibility that diabetes mellitus may be beneficial for patients with severe AIP.

Age of Onset↗
PubMed1998

Emerging roles for novel antipsychotic medications in the treatment of schizophrenia.

Antipsychotic medications are the mainstay of treatment for schizophrenia. The recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophrenia. It is not yet clear how each different drug will fit within the therapeutic armamentarium and this lack is most evident with considering patients with treatment refractory schizophrenia. On the other hand, the expectation of superior efficacy, more benign side effect profile and potential to impact the longitudinal course of schizophrenia provide a rationale for the use of novel antipsychotics as a first-line treatment of schizophrenia.

Antipsychotic Agents↗
PubMed1998

Selection bias in a study on how women experienced induced abortion.

OBJECTIVE: One third of the women who had an induced abortion at the department of gynecology and obstetrics in Malmö 1989 refused to participate in an interview a year later to explore their experience and the care they had received. Using data from the mandatory preoperative visit it was then possible to compare participants with non-participants with regard to socio-demographic characteristics. reproductive history and stated reason for abortion. By continued follow-up of medical records it has furthermore been possible to ascertain how many women conceived within a year, and how many of them applied for another abortion and how many elected to continue the pregnancy to term. SETTING: Department of Obstetrics and Gynecology, Lund University, University Hospital, Malmö Sweden. This is the sole referral hospital serving the population of Malmö (approx. 230000). SUBJECTS: All 1285 women who underwent induced abortion at the department in 1989. + STUDY DESIGN: In each case information on socio-demographic characteristics, reproductive history and stated reasons for abortion was collected at the mandatory clinical visit prior to the abortion. This information was used for comparison of participants and non-participants in the planned 1-year follow-up interview. RESULTS: Young, unmarried women of low educational status and without full-time employment or studying were overrepresented in the non-participant group. The proportion of women with children was however smaller in that group. Within 12 months after the abortion, 118 women 66 (7.7%) of the participants in the follow-up interview and 52 (12%) of the non-participants conceived again but elected to continue the pregnancy to term (P<0.05). whereas 124 of the women 80 (9.5%) and 44 (10.2%) of the respective subgroups again applied for abortion within 12 months. CONCLUSION: One third of the women who underwent induced abortion did not wish to be interviewed about their emotional and somatic experience of the abortion 1 year later. Non-participation at the follow-up interview was associated with socio-demographic factors which in studies about other medical problems have been shown to be associated with increased vulnerability and morbidity. Non-participation was also associated with an increased childbirth rate during the following 2 years. The large proportion of non-participants is a matter for concern as to some extent it reflects inability of the health care system to establish trustful relationships with these women. How the participants in the follow-up study experienced this relationship will soon be published in our next paper. Support from the women's surroundings and the adviser the women met at the public health care system clearly influenced the women's psychological reactions after the abortion. It is therefore important to ascertain to what extent the management of abortion applicants in fact fulfils their individual needs and expectations.

Abortion, Induced↗
PubMed1997

Structural and functional aspects of rat microsomal glutathione transferase. The roles of cysteine 49, arginine 107, lysine 67, histidine, and tyrosine residues.

Rat liver microsomal glutathione transferase is rapidly inactivated upon treatment with the arginine-selective reagent phenylglyoxal or the lysine-selective 1,3,5-trinitrobenzenesulfonate. Glutathione sulfonate, an inhibitor of the enzyme, gives nearly complete protection against inactivation and prevents modification, indicating that these residues form part of or reside close to the active site. Sequence analysis of peptides from peptic and tryptic digests of [7-14C]phenylglyoxal- and 1,3,5-trinitrobenzenesulfonate-treated microsomal glutathione transferase indicated arginine 107 and lysine 67 as the sites of modification. A set of mutant forms of microsomal glutathione transferase was constructed by site-directed mutagenesis and heterologously expressed in Escherichia coli BL21(DE3). Arginine 107 was exchanged for alanine and lysine residues. The alanine mutant (R107A) exhibited an activity and inhibition profile similar to that of the wild type enzyme but displayed a decreased thermostability. Thus, arginine 107 does not appear to participate in catalysis or substrate binding; instead, an important structural role is suggested for this residue. Lysine 67 was mutated to alanine and arginine with no effect on activity. All three histidines were replaced by glutamine, and the resulting mutant proteins had activities comparable with that of the wild type. It can thus be concluded that the chemical modification experiments indicating that arginine 107, lysine 67, and one of the histidines partake in catalysis can be disproved. However, protection from modification by a competitive inhibitor indicates that these residues could be close to the glutathione binding site. All tyrosine to phenylalanine substitutions resulted in mutants with activities similar to that of the wild type. Interestingly, the exchange of tyrosine 137 appears to result in activation of the enzyme. Thus, the microsomal glutathione transferase must display an alternate stabilization of the thiolate anion of glutathione other than through interaction with the phenolic hydroxyl group of a tyrosine residue. Substitution of cysteine 49 with alanine resulted in a semiactivated mutant enzyme with enzymatic properties partly resembling the activated form of microsomal glutathione transferase. The function of this mutant was not altered upon reaction with N-ethylmaleimide, and cysteine 49 is thus demonstrated as the site of modification that results in activation of microsomal glutathione transferase.

Amino Acid Sequence↗
PubMed1997

Hydroxylamine-induced cleavage of the asparaginyl-glycine motif in the production of recombinant proteins: the case of insulin-like growth factor I.

Hydroxylamine-induced cleavage at the asparaginyl-glycine dipeptide site inserted between the two moieties of recombinant fusion proteins has been used at both the analytical and the preparative scale to obtain the mature protein. In this study a model protein containing a fusion precursor of insulin-like growth factor I was used to investigate the influence of the operating conditions on the cleavage reaction and the formation of undesired side products such as hydroxamate and deamidated analogs. Moreover, the stability of the cleavage site toward deamidation was examined and a chemometric study performed to define the effect of the reaction conditions on the cleavage yield and on the formation of side products.

Amino Acid Sequence↗