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Biomedical subjects

C Ericsson

Publications and source records attributed to C Ericsson.

At least 19 recordsLinked to original sources

Diastereocontrol by trialkylaluminums in the synthesis of tetrahydrofurans via radical cyclization.

[reaction: see text]. The influence of various Lewis acids in the radical cyclization of beta-allyloxyalkyl phenyl selenides was investigated. Whereas the unperturbed cyclization afforded trans-2,4-disubstituted tetrahydrofurans as the major products (cis/trans approximately 1/4.5), cyclization in the presence of trialkylaluminums (3 equiv) afforded predominantly (cis/trans approximately 7/1) the corresponding cis-isomers.

Journal Article↗

Association of HLA class I and class II antigen expression and mortality in uveal melanoma.

PURPOSE: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLA antigens mediate interactions of tumor cells with T cells and NK cells. Uveal melanoma is a highly malignant tumor of the eye and is characterized by a hematogenic spread to the liver. Little is known about the role of HLA expression in progression of this malignant disease. METHODS: In the present study HLA class I antigen, beta(2)-microglobulin (beta(2)-m), and HLA class II antigen expression was analyzed in primary uveal melanoma lesions by immunoperoxidase staining with monoclonal antibodies of 65 archival clinical samples. The results were correlated with the clinical course of the disease. RESULTS: HLA class I antigen expression and beta(2)-m expression were downregulated in 40 and 35 lesions, respectively. HLA class II antigens were expressed in 30 lesions. Patients with high HLA class I, including beta(2)-m, and HLA class II antigen expression in their primary melanoma lesions had a significantly decreased survival (P = 0.009, P < 0.001, and P = 0.006, respectively). CONCLUSIONS: The findings argue against a major role of cytotoxic T-lymphocyte (CTL)-mediated control of tumor growth in the clinical course of uveal melanoma and are compatible with a potential role of NK-cell-mediated control of hematogenic metastatic spread.

Adult↗

Kidney donors don't regret: follow-up of 370 donors in Stockholm since 1964.

BACKGROUND: The aim of the study was to present the views of our kidney donors since 1964, at the time of donation, as well as later on--and to assess their current subjective health. METHODS: A total of 451 living-donor nephrectomies were performed on Swedish residents in Stockholm from April 1964 until the end of 1995. A questionnaire with 11 questions about the donation and a standardized health form (SF-36) were sent to all donors alive in 1997 (n=403). RESULTS: The mean age (+/-SD) of the donors was 61+/-14 years at follow-up and the time-since-donation was 12.5+/-7.7 years. The response rate was very good (92%). Current health, as assessed by form SF-36, was satisfactory. Donors scored somewhat better than those reported in a random sample of the Swedish population. The decision to donate had been easy: 86% made the decision themselves, without being pushed. Twenty-three percent thought that the nephrectomy had been troublesome. A higher percentage of young donors had felt that the postoperative period was difficult. Most donors (56%) stated that it had taken more than 2 months before they returned to a "normal" life, and 5% felt that they never completely recovered. Less than 1% of the donors regretted the donation. The commonest current medical prescription was antihypertensives (15%). The actual mean serum creatinine was 103+/-22 (range 48-219) micromol/L. CONCLUSIONS: The results indicate that the degree of health is at least as high as in the general population. The decision to donate was easy for most of the donors, but surgery and the recovery period were troublesome and lasted longer than expected. Kidney function was acceptable.

Adult↗

Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.

We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.

Amino Acid Sequence↗

Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group.

BACKGROUND: Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control. OBJECTIVE: To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections. DESIGN: Multicenter, randomized clinical trial. SETTING: Five university-based medical centers. PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters. INTERVENTION: 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls. MEASUREMENTS: Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections. RESULTS: The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs. CONCLUSIONS: Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.

Adolescent↗

Islet cell antibodies, but not glutamic acid decarboxylase antibodies, are decreased by plasmapheresis in patients with newly diagnosed insulin-dependent diabetes mellitus.

The effects of plasmapheresis on islet autoantibody levels, C-peptide (beta-cell function), and hemoglobin-A1c (HbA1c, metabolic control) were tested in a prospective blinded study of 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients randomly assigned to receive plasmapheresis (P), carried out as double filtration, or sham (S) treatment at diagnosis and 3 months thereafter. At diagnosis, 6 of 8 patients (75%) in group P and 9 of 10 patients (90%) in group S had islet cell antibodies (ICA), whereas 4 of 8 (50%) and 7 of 10 (70%) patients, respectively, had glutamic acid decarboxylase antibodies (GAD65-Ab), with no significant differences between the groups in ICA and GAD65-Ab levels. After 6 months, P patients showed significantly lower ICA levels than S patients (11 +/- 6 and 128 +/- 47 Juvenile Diabetes Foundation International Units, respectively; P < 0.02) due to an increase in ICA levels in 8 of 9 (88%) of the S patients not seen in P patients (P < 0.002). Concurrently, HbA1c stabilized in P, but not in S, patients and was significantly lower by 24 months (6.58 +/- 0.54% vs. 9.76 +/- 1.21%; P < 0.05). Moreover, fasting C-peptide increased significantly (214 +/- 11 pmol/L; P < 0.05) over the first 6 months in P. After the initial 6 months, ICA levels tended to decrease in all patients and were not detected after 60 months. GAD65-Ab levels were not influenced by plasmapheresis and, also in contrast to ICA, increased significantly (P < 0.05) in the whole study population after 60 months. In fact, 4 initially negative patients became GAD65-Ab positive after diagnosis (in 2 patients > 24 months after diagnosis). We conclude that plasmapheresis of newly diagnosed IDDM patients does not change subsequent GAD65-Ab levels, but ICA are significantly decreased with associated improved C-peptide and HbA1c levels.

Adolescent↗

Latex agglutination-negative methicillin-resistant Staphylococcus aureus recovered from neonates: epidemiologic features and comparison of typing methods.

An unusual strain of methicillin-resistant Staphylococcus aureus (MRSA) was repeatedly isolated from infants in a newborn special care unit (NBSC) and a newborn intensive care unit. Between January 1989 and March 1990, approximately 100 isolates from infected or colonized infants were recovered. Surveillance cultures taken during this time revealed a 20% colonization rate, which was defined as recovery of MRSA from the nares, umbilicus, or groin. Isolates were identified as S. aureus by tube coagulase reactivity and heat-stable nuclease production but were unreactive in a latex agglutination assay. Representative isolates that were collected during the outbreak and that were found to share the latex agglutination assay-negative phenotype were compared by antibiogram (12 isolates), bacteriophage typing (20 isolates), capsular polysaccharide typing (30 isolates), and plasmid as well as chromosomal DNA analyses (20 isolates). All isolates known to be associated with the outbreak had nearly identical antibiograms and were notably susceptible to clindamycin. Staphylococcal bacteriophage typing was not useful in determining the relatedness of the isolates, since the majority were nontypeable. Plasmid pattern analysis revealed one large plasmid (approximately 100 kb) of equivalent size among the isolates. Capsular polysaccharide typing revealed that 14 of 30 isolates tested were type 5. Isolates identified in children at two other hospitals in the city which were also unreactive by the latex agglutination assay and clindamycin susceptible had plasmid and antibiogram patterns identical to those of isolates from the NBSC. Pulsed-field gel electrophoresis of restriction enzyme-digested genomic DNAs from the outbreak isolates demonstrated identical patterns which could be clearly differentiated from those of other unrelated MRSA. The strain from the NBSC is, therefore, unique and underscores the need for caution in interpreting the latex agglutination reactivities of MRSA isolates.

Bacterial Typing Techniques↗

The Balbiani ring 3 gene in Chironomus tentans has a diverged repetitive structure split by many introns.

A set of approximately 15 secretory proteins is synthesized by the salivary gland cells in the midge Chironomus tentans. These proteins are secreted but do not form insoluble fibers until they are transported out of the gland lumen. A Balbiani ring (BR) gene family consisting of four genes (BR1, BR2.1, BR2.2 and BR6) have previously been shown to encode four of these proteins, sp-I a to d, with relative molecular weights of 1 x 10(6). Each BR gene contains an uninterrupted block in which about 100 repeats are tandemly arranged. The repeats are virtually identical and efficient homogenization mechanisms must operate within each block. Here we describe a new BR gene, the BR3 gene, which according to structural similarities may belong to the BR gene family, but at the same time exhibits a strikingly different structure. The gene encodes a 10.9 kb transcript that contains 38 introns and is spliced into a 5.5 kb mRNA. The mRNA is translated into a cysteine-rich 185 kDa major component of the gland secretion. The coding sequence in the gene is built from diverged repeats in which mainly the cysteine codons are preserved and the sequence is split by the introns into 17 to 678-bp long exons. The introns are located at defined positions in relation to the repeat structure. In sharp contrast to the uninterrupted array of identical repeats in the BR1-BR6 genes, the repeats in the BR3 gene are not efficiently homogenized and have diverged extensively from each other. We propose that the splitting of the repeat structure into variable sized exons prevents homogenizations dependent on unequal aligning of homologous sequences.

Amino Acid Sequence↗

Presence of histone H1 on an active Balbiani ring gene.

We have investigated whether histone H1 is present on active Balbiani ring genes in the salivary glands of Chironomus tentans using immunoelectron microscopy. The genes were studied in two activity states: maximally activated genes with a fully extended template and repressed genes in a 30 nm fiber conformation. Histone H1 was recorded on the gene in both conformations; the immunosignal was considerably stronger in the transcriptionally active state, probably reflecting the increased accessibility of histone H1 to the antibody in unfolded versus compacted chromatin. We conclude that during transcription the DNA template is extended and the nucleosomes are disrupted at the RNA polymerases, but histone H1, and most likely also the core histones, remains bound to the template.

Animals↗

A new member of a secretory protein gene family in the dipteran Chironomus tentans has a variant repeat structure.

We describe the structure of a gene expressed in the salivary gland cells of the dipteran Chironomus tentans and show that it encodes 1 of the approximately 15 secretory proteins exported by the gland cells. This sp115,140 gene consists of approximately 65 copies of a 42-bp sequence in a central uninterrupted core block, surrounded by short nonrepetitive regions. The repeats within the gene are highly similar to each other, but divergent repeats are present in a pattern which suggests that the repeat structure has been remodeled during evolution. The 42-bp repeat in the gene is a simple variant of the more complex repeat unit present in the Balbiani ring genes, encoding four of the other secretory proteins. The structure of the sp115,140 gene suggests that related repeat structures have evolved from a common origin and resulted in the set of genes whose secretory proteins interact in the assembly of the secreted protein fibers.

Amino Acid Sequence↗

The ultrastructure of upstream and downstream regions of an active Balbiani ring gene.

When active, the 37 kb Balbiani ring genes are known to form transcription loops with an almost fully extended chromatin axis. Here we examine the upstream and downstream regions of such transcription loops by electron microscopy. We demonstrate that a loop starts and ends in tightly packed chromatin; the two anchoring sites are clearly separated from each other in space. The upstream, nontranscribed region consists of a thin, extended, apparently flexible and nucleosome-free fiber corresponding to about 0.5 kb DNA. The downstream, nontranscribed region appears as a 200 nm long nucleofilament loosely coiled into a short, thick chromatin fiber and estimated to contain about 3 kb DNA.

Animals↗

Inhibition of transcription does not affect the total amount of ubiquitinated histone 2A in chromatin.

Using a polyclonal anti-ubiquitin antibody in Western blotting experiments, we detected three antibody-binding components in a HeLa cell extract: ubiquitin, a ubiquitin-histone 2A conjugate (uH2A) and a 17 kD protein, probably corresponding to an additional ubiquitin conjugate. Since ubiquitination of histone 2A (H2A) has been invoked in the transcription process, the amount of uH2A was studied after inhibition of ribosomal RNA (rRNA) synthesis with actinomycin D and of heterogeneous nuclear RNA (hnRNA) synthesis with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). The amount of uH2A did not change, suggesting that the overall level of ubiquitination of histone 2A is not directly coupled to on-going transcription of either rRNA or hnRNA. Since the uH2A content of protein coding genes constitutes a considerable portion of total chromatin uH2A, it seems also likely that there is no major change in the degree of ubiquitination on the templates of the protein-coding genes themselves upon cessation of transcription. It is proposed that the pattern of ubiquitination of histone 2A is established on a long-term basis and that it is related to the overall organization and distribution of the chromatin material in the interphase nucleus.

Chromatin↗

Low degree of ubiquitination of histone 2A in the dipteran Chironomus tentans.

A polyclonal antibody to ubiquitin has been prepared and shown to react with both ubiquitin and ubiquitinated histone 2A (uH2A). Applying this antibody in Western blotting experiments, we have observed that the salivary glands of Chironomus tentans contain an unusually low amount of uH2A (1% of histone 2A), while the amount of free ubiquitin is as abundant as in other animal cells, e.g. HeLa cells. The same low content of uH2A was also found in diploid epidermal cells of Chironomus origin suggesting that the low amount is not a characteristic of the polytene state of chromatin in salivary gland cells but rather a property of C. tentans as a species. The significance of the low degree of ubiquitination is discussed in relation to the information available on the organization of Chironomus chromatin into unusually large chromomeric entities.

Animals↗