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Biomedical subjects

I Andersson

Publications and source records attributed to I Andersson.

At least 109 records · Page 6Linked to original sources

Residues in three conserved regions of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase are required for quaternary structure.

To explore the role of individual residues in the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 4.1.1.39), small subunits with single amino acid substitutions in three regions of relative sequence conservation were produced by directed mutagenesis of the rbcS gene from Anabaena 7120. These altered small subunits were cosynthesized with large subunits (from an expressed Anabaena rbcL gene) in Escherichia coli. Mutants were analyzed for effects on quaternary structure and catalytic activity. Changing Glu-13S (numbering used is that of the spinach enzyme) to Val, Trp-67S to Arg, Pro-73S to His, or Tyr-98S to Asn prevented accumulation of stable holoenzyme. Interpretation of these results using a model for the three-dimensional structure of the spinach enzyme based on x-ray crystallographic data suggests that our small subunit mutants containing substitutions at positions 13S and 67S probably do not assemble because of mispairing or nonpairing of charged residues on the interfacing surfaces of the large and small subunits. The failure of small subunits substituted at positions 73S or 98S to assemble correctly may result from disruption of intersubunit or intrasubunit hydrophobic pockets, respectively.

Amino Acid Sequence↗

Radiographically guided fine-needle aspiration of nonpalpable breast lesions.

Radiographically guided fine-needle aspiration (X-FNA) in 215 nonpalpable, mammographically detected breast lesions was performed by means of a coordinate-grid localization system. Aspirates were categorized either into four cytologic groups or as simple cysts. Based on the most stringent cytologic criteria, the maximum sensitivity for detection of carcinoma was 97% and the specificity was 94%. However, according to these strict cytologic criteria, only 46% of aspirates contained representative material. Based on less stringent cytologic criteria, the maximum sensitivity was 68% and the specificity was 97%. Forty-one of 74 lesions proved to be malignant at biopsy. Thirty-four patients did not complete adequate mammographic follow-up. High sensitivity and specificity can be achieved with X-FNA. However, management decisions ultimately require integration of mammographic findings with cytologic results. Close cooperation among mammographer, surgeon, cytopathologist, and patient is mandatory for successful results.

Biopsy, Needle↗

Stereotactic fine-needle aspiration for cytologic diagnosis of nonpalpable breast lesions.

Fine-needle aspiration for cytologic diagnosis was performed on 219 nonpalpable breast lesions by using a stereotactic localization technique. Cytologic results were correlated with mammographic findings, and therapeutic decisions were based on the results of both procedures. Representative cytologic material was obtained in 74% of the lesions. Strict criteria of representativeness were observed. If only cases with representative cytologic yield are considered, the sensitivity was 93% and the specificity was 97%. The predictive values were high except for the predictive value of a negative cytologic finding in a spiculated lesion (50%). Sampling errors caused by abundant fibrosis, needle deviation, and difficulty in defining the lesion on the stereoscopic views are discussed. Another source of sampling error may be the mixed nature of some lesions consisting of benign and malignant components. Fine-needle aspiration of 219 nonpalpable breast lesions by using a stereotactic localization device yielded representative cytologic samples in 74% of the lesions.

Biopsy, Needle↗

Synthesis of 8-substituted derivatives of the 2-deoxy analogue of 3-deoxy-beta-D-manno-2-octulopyranosonic acid (2-deoxy-beta-KDO) as inhibitors of 3-deoxy-D-manno-octulosonate cytidylyltransferase.

The 2-deoxy analogue of 3-deoxy-beta-D-manno-2-octulopyranosonic acid (2-deoxy-beta-KDO, 2) is a potent inhibitor of the enzyme 3-deoxy-D-manno-octulosonate cytidylyltransferase, which is involved in the biosynthesis of lipopolysaccharide, an essential component of the outer membrane of Gram-negative bacteria. Since compound 2 lacks antibacterial activity, a series of 8-substituted derivatives of 2 has been synthesized in an attempt to find enzyme inhibitors suitable for modification as antibacterials. Compounds 9, 11, and 13, in which the 8-hydroxy group of 2 is replaced by F, H, and NH2, respectively, were as potent inhibitors of the enzyme as 2, but were devoid of antibacterial activity, with the exception of the amino acid 13, which showed weak activity against some strains of Salmonella typhimurium.

Anti-Bacterial Agents↗

Dissection of the human antibody response to the malaria antigen Pf155/RESA into epitope specific components.

The development of vaccines is presently receiving major attention in malaria research. As it is not possible to base malaria vaccines on the use of killed or attenuated organisms, the vaccines which are being developed are subunit vaccines in which the immunogens consist of defined parasite antigens or antigenic fragments. Since protective immunity to malaria involves both antibody-dependent and antibody-independent mechanisms, the immunogens in a subunit vaccine must have the capacity to induce relevant B- and T-cell responses in the majority of vaccinees. In turn, this requires good knowledge of these responses in humans who have acquired immunity through natural infection. In this paper we have summarized our recent work on the dissection into epitope-specific components of the human antibody response to the Plasmodium falciparum antigen Pf155/RESA, a recognized candidate for a vaccine against the asexual blood stages of this parasite. Epitope mapping of the antigen by means of short synthetic peptides led to the identification in several molecular regions of short amino acid sequences constituting linear and probably immunodominant B-cell epitopes. The antigenically most active region was located in the C-terminus of the molecule. This region, which consists of approximately 40 related, 4- or 8-amino acid long repeats, induced higher antibody concentrations in a larger number of malaria-immune donors than any of the other regions. A large fraction of these antibodies bound to short synthetic peptides representing the major repeat motifs of Pf155/RESA. Although these repeats are made up of closely related amino acid sequences, the antibody response to them was highly polyclonal, indicating the presence of several linear and probably also conformational epitopes which gave rise to a variety of cross-reacting as well as monospecific antibodies. Further analysis revealed that the levels of antibodies differing in specificity and/or avidity for different peptides varied independently of each other in individual donors. In an area (Liberia) where malaria transmission is holoendemic and perennial, these antibody profiles remained constant when individual donors were followed over several years. Since the C-terminal repeat region of Pf155/RESA is conserved in different P. falciparum strains, the results reflect differences in the genetic regulation of epitope-specific host responses rather than antigenic differences between infecting parasites. In donors living in an area with high but seasonal malaria transmission, antibody levels usually drop to lower levels when there is no transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Ductal carcinoma in situ: atypical mammographic appearances.

The authors retrospectively analyzed the mammograms of 190 women with biopsy-proved ductal carcinoma in situ (DCIS). Excluded from the current study were 117 (62%) women whose radiographs showed suspicious clustered microcalcifications, a well-known finding in DCIS. Of the remaining 73 (38%) women, 30 (16%) had negative mammograms, and 43 (23%) had mammographic manifestations of breast malignancy other than microcalcifications. Of the latter 43, 15 had circumscribed masses, and 12 had various focal nodular patterns. The remaining 16 patients showed other mammographic signs of malignancy, including asymmetry (n = 1); dilated retroareolar ducts (n = 2); ill-defined, rounded tumor (n = 2); focal architectural distortion (n = 4); subareolar mass (n = 3); and developing density (n = 4). Of the 73 women in the study, 60 presented with clinical findings related to the tumor. Since DCIS has a high survival rate with proper treatment, radiologists should be aware of the unusual radiographic manifestations of this disease.

Adult↗

Energy intake of obese women.

In connection with a weight reduction study over 12 weeks we included a dietary history of obese women before and during the study. The first interview was geared to find out their usual energy intake, the second to monitor compliance. All interviews were performed in the homes of the obese women by the same research dietitian. A pilot study was carried out in the spring with 19 women. The subsequent complete study was performed in the autumn when 33 women were interviewed. After the first interview, the women were taught to eat 1500 kcal/day. The anthropometric data of women in the spring and autumn group were similar. The mean energy intake calculated from the first spring interview was 2203 +/- 643 (s.d.) kcal/day, range 1053-3474 kcal, whereas the daily intake in the autumn group was 2805 +/- 803 kcal/day, range 1113-4042 kcal (P less than 0.01). Thus, after a pilot study a 27 per cent higher energy intake could be revealed in a group of obese women. The second dietary history showed a good compliance with the programme in both spring and autumn groups with a calculated daily intake of 1535 +/- 363 kcal, range 984-2612 kcal, and 1639 +/- 481 kcal, range 616-2995 kcal respectively and an accompanying weight loss of 5.7 +/- 4.1 kg and 4.9 +/- 3.0 kg. Our data indicate that after a dietitian run-in period a substantially higher energy intake can be detected in obese women than has generally been reported.

Energy Intake↗

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

STUDY OBJECTIVE: To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN: Birth year cohorts of city population separately randomised into study and control groups. SETTING: Screening clinic outside main hospital. PATIENTS: Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS: Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT: Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS: All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS: In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS: Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Age Factors↗

X-ray guided fine-needle aspiration for the cytologic diagnosis of nonpalpable breast lesions.

X-ray guided localization of 215 nonpalpable, mammographically detected, breast lesions for fine-needle aspiration biopsy was performed using a two-dimensional coordinate grid. Representative material was obtained in 64% of the lesions. Very strict criteria of representativity were observed. The sensitivity of the cytologic procedure was 92%, the specificity 95%, the predictive value of positive cytologic diagnosis 88%, and the predictive value of a negative cytologic diagnosis 97%. Potential pitfalls in the localization and aspiration procedures are discussed. The results of cytologic examination should always be correlated with the mammographic findings, and further diagnostic and therapeutic decisions should be based on both modalities. In this setting, x-ray guided fine-needle aspiration cytologic study is a highly valuable diagnostic tool.

Biopsy, Needle↗

Feeding green-cut forage contaminated by radioactive fallout to dairy cows.

Grass contaminated by radioactive fallout from the Chernobyl accident was cut with 150 mm (Treatment 1) and 50 mm (Treatment 2) stubble height and fed to 20 dairy cows. The transfer of 137Cs and 131I from the greencut forage to milk was studied during a four-week and a two-week period, respectively. The four-week period was followed by a three-week period with nearly uncontaminated feeds. Cutting with high stubble height significantly reduced the activity concentration in forage compared with low stubble cutting, the average contents kg-1 dry matter being 385 Bq 137Cs and 24 Bq 131I in Treatment 1 versus 6656 Bq 137Cs and 249 Bq 131I in Treatment 2. Apparent treatment effects were also demonstrated by the 137Cs concentration in milk, with maximum weekly means of 23 Bq kg-1 (Treatment 1) and 92 Bq kg-1 (Treatment 2). Single day maximum concentrations of 131I in milk were 4 Bq kg-1 (Treatment 1) and 9 Bq kg-1 (Treatment 2). The mean transfer coefficients (d kg-1) were calculated to be 0.67 X 10(-2) and 0.19 X 10(-2) for 137Cs (weeks 2-4) and 1.8 X 10(-2) and 0.2 X 10(-2) for 131I (week 2) in Treatments 1 and 2, respectively. The lower value for 137Cs might possibly be associated with an enhanced ash content of the forage. Feeding nearly uncontaminated rations rapidly decreased the 137Cs levels in milk in both treatments with calculated effective half-times over the three-week period of 10 and 7 d, respectively.

Accidents↗

Changes in neck muscles in Swedish reindeer bucks during rutting season.

Three neck muscles in Swedish reindeer bucks have been studied before and during the rutting season. These were M. splenius, M. sternocephalicus and M. brachiocephalicus. For comparison, M. longissimus dorsi was chosen. Fibre composition and fibre size were studied in the four muscles as also was the metabolic potential of three enzymes, representing respiratory chain (cytochrome oxidase), beta-oxidation of fatty acids (3-hydroxyacyl-CoA dehydrogenase) and anaerobic glycolysis (lactate dehydrogenase). The extreme increase in size of certain muscles in the neck in connection with the rutting season (e.g. sternocephalicus, which increases from 250 g to 1,500 g) was to a great extent due to an increase in fibre size. In splenius, all three fibre types studied increased (I, IIA, IIB); in brachiocephalicus, mainly IIA and IIB; and in sternocephalicus, only the IIB. No corresponding fibre increase could be found in longissimus dorsi. In splenius and sternocephalicus from bucks older than 54 months, 60-70% of the fibres were of type I, and in brachiocephalicus, only about 40%. In all muscles but one, oxidative capacity (cytochrome oxidase) and beta-oxidation of fatty acids (3-hydroxyacyl-CoA dehydrogenase) decreased significantly during the rutting season. This indicates that purposes other than the enhancement of energy production by fatty acid oxidation must account for the enlargement of the neck muscles.

3-Hydroxyacyl CoA Dehydrogenases↗