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K Magnusson

Publications and source records attributed to K Magnusson.

46 records · Page 3Linked to original sources
PubMed1986

Nucleotide sequence of the gene for cytochrome b558 of the Bacillus subtilis succinate dehydrogenase complex.

The nucleotide sequence was determined for the first part of the Bacillus subtilis sdh operon. An open reading frame corresponding to the structural gene, sdhA, for cytochrome b558 was identified. The predicted molecular weight of the cytochrome (excluding the N-terminal methionine) is 22,770. It is a very hydrophobic protein with five probable membrane-spanning segments. There is little homology between the B. subtilis cytochrome b558 and cytochrome b of mitochondrial complex III from different organisms or between cytochrome b558 and the hydrophobic sdhC and sdhD peptides of the Escherichia coli sdh operon. About 30 bases downstream of the sdhA stop codon, a new open reading frame starts. The nucleotide sequence predicts the presence of a typical flavin-binding peptide which identifies this reading frame as part of the sdhB gene. Seven bases upstream of the sdhA initiation codon ATG there is a typical B. subtilis ribosome binding site (free energy of interaction, -63 kJ), and further upstream, tentative sigma 55 and sigma 32 promoter sequences were found. The upstream region also contains two 12-base-long direct repeats; their significance is unknown.

Amino Acid Sequence↗
PubMed1985

Cloning and expression in Escherichia coli of sdhA, the structural gene for cytochrome b558 of the Bacillus subtilis succinate dehydrogenase complex.

Bacillus subtilis cytochrome b558 is a transmembrane protein which anchors succinate dehydrogenase (SDH) to the cytoplasmic membrane and is reduced by succinate. The structural gene for this cytochrome was cloned and expressed in Escherichia coli. Random BamHI or BglII fragments of B. subtilis 168 DNA were cloned in the BamHI site of plasmid pHV32. The derived plasmids were used to transform B. subtilis SDH mutants to chloramphenicol resistance by integration of the plasmid via DNA homology. Of some 3,000 transformants tested, 6 were SDH positive and had pHV32 integrated close to the sdh operon. Two plasmids, pKIM2 and pKIM4, with an insert of B. subtilis DNA of 5.7 and 3.4 kilobases, respectively, were generated by transforming E. coli with DNA from the SDH-positive transformants after cleavage with EcoRI or BglII and ligation. In E. coli carrying either of the two plasmids, about 4% of total membrane protein was B. subtilis cytochrome b558. E. coli (pKIM2) also contained antigen which reacted with antibodies specific for the flavoprotein and the iron-sulfur protein subunit of B. subtilis SDH. Enzymatically active, membrane-bound B. subtilis SDH could not be demonstrated in E. coli (pKIM2). The B. subtilis DNA insert in pKIM2 could transform B. subtilis sdhA (cytochrome b558), sdhB (flavoprotein), and sdhC (iron-sulfur protein) mutants to the wild type. The results suggest that pKIM2 carries the whole B. subtilis sdh operon. The data confirm the gene order and the proposed direction of transcription of the B. subtilis sdh operon. Most likely the sdh genes in E. coli(pKIM2) are controlled by their natural promoter.

Antigens, Bacterial↗
PubMed1985

Familial cranial diabetes insipidus: a report of five families. Genetic, diagnostic and therapeutic aspects.

Five families were studied in which cranial diabetes insipidus occurred. In the pedigrees presented, the disease clearly followed an autosomal dominant mode of inheritance. Linkage analysis was performed in one large family by calculating lod scores for linkage between loci for cranial diabetes insipidus and 18 polymorphic markers and chromosome heteromorphisms. No significant genetic linkage was found and only one of the polymorphic markers gave a positive hint of linkage. A water deprivation test was performed in nine patients from three of the families and in healthy control subjects. The plasma concentration of arginine vasopressin was very low or undetectable in the patients, and unlike the control subjects did not increase significantly during water deprivation. Arginine vasopressin and serum osmolality (Sosm) were significantly positively correlated in the controls, but not in the patients. The results indicated that an arginine vasopressin-level lower than 2 pg/ml strongly suggests a diagnosis of cranial diabetes insipidus if at the same time Sosm is higher than 295 mosmol/kg. Studies with different intranasal dosages of 1-deamino-D-arginine-vasopressin (DDAVP) given once or twice a day showed that 20 micrograms effectively reduced urinary output and that administration once a day could be sufficient.

Adolescent↗
PubMed1983

Characterization of a pleiotropic succinate dehydrogenase-negative mutant of Bacillus subtilis.

A succinate dehydrogenase-negative mutant of Bacillus subtilis is described which lacks all three subunits of the membrane-bound succinate dehydrogenase complex: flavoprotein, iron protein, and cytochrome b558. The corresponding mutation is revertible and it maps at one extreme of the sdh region. The results presented suggest that the structural genes for the subunits of the succinate dehydrogenase complex are part of one operon.

Bacillus subtilis↗
PubMed1983

Interferon therapy in recurrent renal carcinoma.

Seven patients with recurrent renal carcinoma, who had previously been treated with progesterone and vinblastine for progressive disease, were treated with human leukocyte interferon (HuIFN alpha). Five patients received daily escalating i.m. IFN doses from 4 X 10 up to 16 X 10(6) U during a minimum of 4 weeks, while two patients received intralesional IFN, 20 X 10(6) U/dose. No serious side-effects were observed. No tumor response was found in any of these patients.

Adenocarcinoma↗
PubMed1982

Reconstitution of succinate dehydrogenase in Bacillus subtilis by protoplast fusion.

Bacillus subtilis succinate dehydrogenase (SDH) is composed of two unequal subunits designated Fp (Mr, 65,000) and Ip (Mr. 28,000). The enzyme is structurally and functionally complexed to cytochrome b 558 (Mr, 19,000) in the membrane. A total of 21 B. subtilis SDH-negative mutants were isolated. The mutants fall into five phenotypic classes with respect to the presence and localization of the subunits of the SDH-cytochrome b558 complex. One class contains mutants with an inactive membrane-bound complex. Membrane-bound enzymatically active SDH could be reconstituted in fused protoplasts of selected pairs of SDH-negative mutants. Most likely reconstitution is due to the assembly of preformed subunits in the fused cells. On the basis of the reconstitution data, the mutants tested could be divided into three complementation groups. The combined data of the present and previous work indicate that the complementation groups correspond to the structural genes for the three subunits of the membrane-bound SDH-cytochrome b558 complex. A total of 31 SDH-negative mutants of B. subtilis have now been characterized. The respective mutations all map in the citF locus at 255 degrees on the B. subtilis chromosomal map. In the present paper, we have revised the nomenclature for the genetics of SDH in B. subtilis. All mutations which give an SDH-negative phenotype will be called sdh followed by an isolation number. The designation citF will be omitted, and the citF locus will be divided into three genes: sdhA, sdhB, and sdhC. Mutations in sdhA affect cytochrome b558, mutations in sdhB affect Fp, and mutations in sdhC affect Ip.

Bacillus subtilis↗
PubMed1982

Combined irradiation and three-drug chemotherapy in inoperable colorectal carcinoma.

Forty patients with inoperable or not radically resected tumours in the rectum or rectosigmoideum were treated with irradiation combined with 5-fluorouracil, methotrexate and cyclophosphamide. The acute toxicity was moderate, but 3 patients developed late complications such as fibrosis and fistulation in the irradiated area. Twenty-one patients had a measurable tumour within the radiation fields and were included in the evaluation of the tumour response. Of these patients 8 achieved complete and 5 partial tumour remission. Nevertheless, it is emphasized that this treatment cannot be recommended because of severe complications observed in a following randomized series of patients receiving irradiation combined with 5-fluorouracil and methotrexate.

Adenocarcinoma↗
PubMedDate not supplied

Effect of quarterly treatments with a chlorhexidine and a fluoride varnish on approximal caries in caries-susceptible teenagers: a 3-year clinical study.

The aim of this study was to compare the effect of two different dental varnishes on approximal caries incidence in teenagers with proven caries susceptibility during a 3-year period. Two hundred 13- to 14-year-old subjects exhibiting at least two approximal enamel caries lesions were selected to take part in the study. One hundred and eighty subjects participated after informed consent and were randomly assigned to two equally sized groups. One group was treated with a fluoride varnish (FV, Fluor Protector) containing 0.1% F every 3rd month and the participants of the other group were treated in the same mode with a chlorhexidine varnish (CV, Cervitec((R))) containing 1% chlorhexidine and 1% thymol. In total, each subject was treated 12 times during the experimental period. Approximal caries including enamel lesions (DMFS(appr)) were recorded from four bitewing radiographs exposed at the start and end of the study. The mean (+/-SD) caries prevalence at baseline was 2.2+/-3.4 in the FV group and 2.5+/-4.0 in the CV group. After 3 years, the average approximal caries incidence was 2.7+/-3.1 and 3.1+/-3.5 in the FV and CV groups, respectively. The differences at baseline and after 3 years were not statistically significant. In conclusion, treatments every 3rd month with either a fluoride- or a chlorhexidine/thymol-containing varnish showed a promising effect with low approximal caries incidence and progression in teenagers with proven caries susceptibility.

Adolescent↗
PubMedDate not supplied

Acute hematologic feasibility of G-CSF supported dose-escalated FEC therapy as adjuvant treatment after breast cancer surgery.

A study of the feasibility of gradually increased epirubicin and cyclophosphamide dosage in an FEC regimen with G-CSF (granulocyte colony stimulating factor) support in 18 high-risk breast cancer patients as adjuvant treatment was carried out. The FEC regimen was initiated with 5-fluorouracil 600 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 900 mg/m2 together with G-CSF 5 micrograms/kg subcutaneously on days 2-15 q 3 weeks for nine cycles, increasing individually through four dose levels to a maximum of 5-FU 600 mg/m2 (not escalated), epirubicin 120 mg/m2 and cyclophosphamide 1800 mg/m2. Transient cytopenias were regularly observed without major clinical complications. Rapid recovery and a biphasic overshoot of granulocytes required individualization of G-CSF support. During the 6-month treatment period, a general decline in granulocytes, platelets and haemoglobin was observed, resulting in maximal dose intensity in the middle of the treatment period. Compared to a conventional FEC regimen (5-Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2, Cyclophosphamide 600 mg/m2 q 3 w) without dose reductions, it was feasible to increase the dose of epirubicin by more than 50 per cent with an increased dose intensity between 25 and 70 per cent. The dose of cyclophosphamide was increased by more than 100 per cent. All patients suffered from complete alopecia and moderate nausea, but there was no acute cardiac or severe mucosal toxicity. It was concluded that intensified, G-CSF supported FEC therapy can be safely administered in an outpatient setting, provided the patients are thoroughly informed and adequately monitored. High-risk patients are enrolled in a study comparing the described regimen and a myeloablative regimen including peripheral stem-cell support. Breast cancer seems to respond to chemotherapy in a dose dependent manner, suggesting the use of dose intensified regimens (1,8,9,11). This approach is currently under investigation in studies comparing standard regimens with myelo-ablative regimens in high-risk primary breast cancer (3,10). In a Scandinavian multicenter study (2), two high dose regimens, G-CSF supported dose-escalated FEC and myeloablative cyclophosphamide-thiotepacarboplatin with peripheral stem cell support, are compared as adjuvant therapy in operable high-risk breast cancer. This phase I study was performed to assess the feasibility and achievable dose intensity of an individually dose-escalated FEC regimen not in previous use.

Adult↗