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Biomedical subjects

B Norberg

Publications and source records attributed to B Norberg.

At least 37 records · Page 2Linked to original sources

Serum homocysteine and methylmalonic acid in patients with rheumatoid arthritis and cobalaminopenia.

OBJECTIVE: To analyze the significance of cobalaminopenia (< 200 pmol/l) in patients with severe rheumatoid arthritis (RA). METHODS: We studied 42 patients with RA and cobalaminopenia (incidence 4%). Most patients had severe and longstanding disease. Concentrations of homocysteine, methylmalonic acid (MMA), gastrin, and pepsinogen 1 were analyzed in sera that had been stored frozen. A capillary gas chromatographic mass spectrometric technique was used to determine homocysteine and MMA. RESULTS: As a group, patients had significantly higher levels of serum homocysteine and serum MMA than laboratory reference probands (p < 0.0001 and p < 0.005, respectively). Individually, 20 of 39 patients had elevated serum levels of homocysteine (> 15 micromol/l). In 12 of 39 patients serum levels of MMA were elevated (> 0.37 micromol/l). Twenty of 42 patients had biochemical signs of disturbed gastric function. CONCLUSION: Our findings were compatible with the hypothesis that cobalaminopenia is one of several biochemical signs of gastrointestinal dysfunction in patients with severe RA. It is suggested that the hyperhomocysteinemia associated with vitamin B12 deficiency, folate deficiency, vitamin B6 deficiency, and impaired renal function may have a role in promoting high cardiovascular morbidity in patients with RA.

Adult↗

Isolation, characterization, and radioimmunoassay of Atlantic halibut somatolactin and plasma levels during stress and reproduction in flatfish.

Somatolactin (SL), a recently identified teleost pituitary hormone which is a member of the growth hormone/prolactin family, was isolated from pituitary tissue of Atlantic halibut (Hippoglossus hippoglossus). Pituitary proteins were extracted in ammonium bicarbonate (pH 7.8), fractionated using gel filtration chromatography, and purified using reversed-phase high-performance liquid chromatography. Halibut SL was identified on the basis of molecular size (determined by gel electrophoresis and mass spectroscopy), cross-reactivity of the putative hormone with antisera to cod SL, and N-terminal amino acid sequence. Polyclonal antibodies to purified halibut SL were raised in rabbits, and a radioimmunoassay (RIA) was developed for measurement of plasma concentrations of SL using purified halibut SL as a standard. The RIA was tested in several flatfish species including Pacific halibut (Hippoglossus stenolepis), English sole (Pleuronectes vetulus), and rock sole (Lepidopsetta bilineata). The assay was specific for SL as indicated by absence of cross-reactivity with Atlantic halibut growth hormone, prolactin, and GTH alpha subunit. Dilutions of plasma and pituitary extracts from Pacific halibut, English sole, and rock sole were parallel to the Atlantic halibut SL standard curve, indicating that the assay is valid for a range of flatfish species. Using halibut SL antiserum, SL was localized in the pars intermedia of English sole pituitary, where it has been identified in previously examined teleost species. The RIA was used to measure plasma levels of SL in Atlantic halibut and English sole during reproductive development, and in English sole subjected to various types of environmental stressors, including handling and crowding. In both sole and halibut, plasma SL concentrations remained relatively constant throughout gonadal development, but dropped during or following ovulation. Plasma SL levels in English sole tended to increase in response to acute stress, in parallel with plasma cortisol levels.

Amino Acid Sequence↗

Synthesis, structure and biological properties of Z-17alpha-(2-iodovinyl)-11beta-chloromethyl estradiol-17beta (Z-CMIV), a high affinity ligand for the characterization of estrogen receptor-positive tumors.

Linkage of a 11beta-chloromethyl group to estradiol-17beta (E2) dramatically increases the binding affinity of the steroid for the estrogen receptor (ER) with the formation of a quasi-irreversible steroid-receptor complex. We have synthesized the two isomers of 11beta-chloromethyl-17alpha-iodovinyl-estradiol (E-CMIV and Z-CMIV) by a novel route. Both derivatives demonstrated high binding affinity and selectivity for ER (RBAs: ER = 820 and 1008; SHBG = 1.2 and 0.25, respectively; E2 = 100). On the basis of X-ray crystallographic data for Z-CMIV and its precursor, we have postulated that Z-CMIV might interact strongly with aromatic amino-acids within a hydrophobic groove of the ER hormone binding domain (HBD) that incorporates pockets corresponding to the 11beta and 17alpha steroid substituents. The binding properties of Z-CMIV labeled with 125I were investigated, especially its ability to detect and quantify altered ER forms with low binding affinity for E2. Sucrose density gradient analysis revealed that Z-CMIV has a higher activation potency than E2 as it converts a higher proportion of non-activated monomers in the cytosol into activated monomers with the potential to dimerize. In in vitro (MCF-7 cells) and in vivo (rat uterus) determinations of estrogenic activity, Z-CMIV was as potent as E2 in increasing progesterone receptor (PgR) concentrations and decreasing ER levels and in stimulating uterine growth. [125I]-Z-CMIV could open the way to new applications in the diagnosis and therapy of ER-positive breast cancers, especially those containing altered (variant) ERs.

Adenocarcinoma↗

Oral anticoagulant treatment in a medical care district--a descriptive study.

OBJECTIVE: To describe how oral anticoagulant therapy is performed in a defined catchment area in order to improve the quality of care. DESIGN: Two study periods of 8 weeks were compared with reference to monitoring sites, i.e. hospital departments and primary health care centres. SETTING: The health care district of Umeå in northern Sweden, with 125,300 inhabitants. PARTICIPANTS: Patients on oral anticoagulant therapy at the department of Internal Medicine, Umeå University Hospital, in 1987 (n = 243) were compared with all patients treated in 1990 at health centres (n = 175) and at the department of Internal Medicine (n = 290) in the Umeå district. MAIN OUTCOME MEASURES: The prevalence of treatment failures and complications was calculated per patient year, as well as the relative frequencies of patients within treatment recommendations. RESULTS: 80-83% of the patients were within treatment recommendations. Treatment failures were 3.6% of hospital patients, and 2.6% of primary care patients. Corresponding figures for bleeding complications were 8.9% and 5.1%, respectively. The differences are partly explained by differences in the studied groups, e.g. age, indications for treatment, and concomitant diseases.

Administration, Oral↗

Cell cycle effects of the anti-rheumatic agent CPH82.

The benzylidated podophyllotoxin glycoside CPH82, a potentially useful drug for treatment of RA, was tested in vitro on nine human haematopoietic cell lines for cell kinetic effects. Previous studies have shown CPH82 to behave like a colchine-type 'metaphase' blocker. The distribution of cells within different cell cycle compartments (G1, S, G2 and M) was analysed by a novel method using dual parameter flow cytometric analysis of stage specific antigens (proliferating cell nuclear antigen and Ki-67). With CPH82 concentrations chosen to mimic clinical conditions, eight out of nine lines showed an accumulation of cells in the G2 phase of the cell cycle. In many lines a delayed progress through S seemed to occur. Three lines were blocked in both G1 and G2, whereas the major effect on one line (HL-60) was an accumulation of cells in the G1 phase. Progression of M cells seemed only slightly delayed for some cell lines. In comparison with two related 'metaphase' blocking agents (podophyllotoxin and taxol), CPH82 had a different and dose-dependent pattern of cell cycle retardation. It is speculated that the cell kinetic action of CPH82 might give insight into the question why it, unlike other 'metaphase' blockers, has proved valuable in the treatment of RA.

Anti-Inflammatory Agents, Non-Steroidal↗

Hodgkin's disease in northern Sweden 1971-1981. I. A histopathological reevaluation of 223 cases.

A histopathological reexamination was made of diagnostic material in 223 patients with Hodgkin's disease (HD) collected between 1971 and 1981. The diagnosis of HD was considered to be incorrect in 90 cases (40%). Change of diagnosis to non-Hodgkin's lymphoma was made in 56 cases, of which 23 were high-grade and 26 were low-grade lymphomas (7 not determined), and to angioimmunoblastic lymphadenopathy in 10 cases. These discrepancies were considered to be due mainly to progress in the understanding and classification of malignant lymphomas, which stresses the importance of review of histologic material in retrospective studies on Hodgkin's disease.

Follow-Up Studies↗

Hodgkin's disease in northern Sweden 1971-1981. II. A retrospective analysis of prognostic factors.

Factors relevant for prognosis were retrospectively studied in a series of 133 morphologically reviewed patients with Hodgkin's disease collected between 1971 and 1981. For the whole material complete remission rate was 74% and 5-year survival was 62%. These seemingly rather poor results could be explained by a high mean age (48 years) in this relatively unselected material, in combination with a very unfavourable outcome for the elderly patients. In a multivariate analysis of prognostic factors age of the patient turned out to be the only independent factor with a significant bearing on the prognosis.

Adolescent↗

Hodgkin's disease in northern Sweden 1971-1981. III. The clinical and prognostic impact of age.

A retrospective material of 133 patients with Hodgkin's disease treated between 1971 and 1981 was analysed. In part II of this study it was shown that the prognosis was closely associated with age of the patient. In this part some clinical factors, including therapy, were compared between 66 patients less than 50 years of age and 67 patients 50 years or more. The groups differed mainly in the outcome of primary chemotherapy. Older patients with Hodgkin's disease were particularly vulnerable to chemotherapy, probably as an effect of the disease itself.

Adolescent↗

The role of sex and age in yeast cell phagocytosis by monocytes from healthy blood donors.

Possible sex differences and possible age decline of monocyte phagocytosis was studied in healthy blood donors (n = 306). Monocytes from women phagocytosed yeast cells more efficiently than monocytes from men, but the difference was slight. The sex difference was located mainly in the adherence step of phagocytosis. In contrast, no age decline in monocyte phagocytosis could be demonstrated within the age range (18--65 years) represented by healthy blood donors. It is suggested that sex difference and age decline are negligible in the phagocytosis by monocytes from healthy blood donors.

Adolescent↗