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Biomedical subjects

C Rasmussen

Publications and source records attributed to C Rasmussen.

At least 55 records · Page 3Linked to original sources

Structure-function analysis of the Autographa californica multinucleocapsid nuclear polyhedrosis virus homologous region palindromes.

Homologous regions (hrs), which are present at eight dispersed locations on the Autographa californica multinucleocapsid nuclear polyhedrosis virus genome, are composed of repeated imperfect palindromes within directly repeated sequences. Hrs act as transcriptional enhancers of RNA polymerase II-mediated transcription and as origins of DNA replication when incorporated into plasmids and tested in transient replication assays. To characterize the physical structure of these elements and to determine the role that mismatched nucleotides may play in hr function, oligonucleotides containing a consensus mismatched "imperfect" palindrome and a closely related "perfect" palindrome were synthesized. These sequences were cloned into individual plasmids and tested for their ability to form cruciform structures using nuclease P1 assays and two-dimensional (2-D) gel analyses of topoisomers. The perfect palindrome formed a cruciform structure and the energy requirement for its formation was predicted to occur under physiological conditions. In contrast, the construct containing an imperfect palindrome did not form a cruciform under these conditions. Both hr constructs were found to bind IE-1 in electrophoresis mobility shift assays and act as enhancers when cis-linked to the baculovirus 39K early gene promoter. However, a single oligonucleotide containing the palindrome sequence did not bind IE-1 when annealed under conditions conducive to hairpin formation.

Animals↗

Lumbar disc herniation: social and demographic factors determining duration of disease.

The study was set up to show whether certain social and demographic characteristics play any significant role in determining the duration of disease in patients with lumbar disc herniation. The study included 171 consecutive patients operated upon for the first time for lumbar disc herniation over a 1-year period. Records were made of each patient's age, sex, domicile (town, rural area), social group and employment status. For each patient, four dates were also recorded: onset of symptoms, referral to hospital, operation and recovery. On this basis six periods could be calculated. Statistical analysis was used to identify the relation between the social and demographic factors and the various time periods between the onset of symptoms and recovery. Being employed, especially in a higher social group, cuts down the period from onset of symptoms to recovery. This shortening in the total duration mainly takes place between onset of symptoms and referral to hospital. The influences of domicile, age and sex were of no statistical significance. The median of the total period from onset of symptoms to recovery was 224 days. Among patients operated upon for the first time for lumbar disc herniation, employment denoted faster referral to hospital and thus faster operation and recovery. Among those employed, the patients from higher social groups were referred quickest.

Adult↗

Acute surgical treatment of complicated peptic ulcers with special reference to the elderly.

The results of 136 consecutive patients treated surgically for the acute complications of peptic ulcers between 1990 and 1993 are reviewed. All patients required emergency operation. Among 136 patients, 91 had perforations, 42 hemorrhage, and 3 a penetrated peptic ulcer. The median age was 77 years; 65% were women; and 83% were more than 60 years old. Concurrent disease requiring medical treatment were present in 92 patients; 79 patients (58%) were currently or recently taking antiinflammatory drugs at the time of admission; 66% of the patients had duodenal ulcer. Only 46 patients (34%) had no postoperative complications; pneumonia, arrhythmia, bleeding, and septic complications were the most frequent. The overall mortality was 30%. Sepsis and multiple organ failure was the leading cause of death in most of the patients. It was concluded that elderly individuals using two or more antiinflammatory drugs should be considered potential peptic ulcer patients and should be treated prophylactically with ulcer-healing drugs.

Age Factors↗

[Fatal cases of poisonings among drug addicts in the county of Funen in 1993].

This study includes death from poisoning among drug addicts in 1993 in the county of Funen, in all 24. The development during the last five years shows an increase, especially in the largest city in the county. The drug addicts have several problems, and several of them were well-known in the social welfare system or by the police. Half of the drug addicts had received treatment for their abuse and three persons were receiving treatment at the time of their death. A few--primarily among the youngest--had only used drugs for a short time while one third had abused drugs for several years. The greater part of the deaths were caused by heroin, which is found in different concentrations in the illegal market. Five of the dead persons had just been released from prison and three people had just left 24-hour care centres when they were found dead. Co-operation between the various, treating authorities has to be given a high priority.

Adolescent↗

Regulation of calcineurin gene expression in Schizosaccharomyces pombe. Dependence on the ste11 transcription factor.

Calmodulin and its target enzymes are important regulators of numerous cellular processes, including reversible protein phosphorylation. The calmodulin-dependent protein phosphatase (calcineurin) has been suggested to play roles in activation of T cells and in the mating response of yeast. Recently, studies have shown it to be the target of immunosuppressant drugs such as cyclosporin and FK-506. In this study, we have cloned the gene for the catalytic subunit of calcineurin, CnA, from the yeast Schizosaccharomyces pombe. The gene (named ppb1+) has been mapped to chromosome II by analysis of the hybridization of a genomic DNA probe to an ordered library. The gene produces a single mRNA species of 2.5 kilobases, which varies during the cell cycle in exponentially growing cells. In addition, expression of ppb1+ mRA is induced by nitrogen starvation, a condition that favors mating in S. pombe. The ppb1+ gene promoter contains a cis-acting element for the ste11 transcription factor, and we have shown that induction of the ppb1+ mRNA during nitrogen starvation is dependent on the ste11 gene product. Together with earlier studies showing that disruption of the ppb1+ gene in S. pombe results in sterility (Yoshida, T., Toda, T., and Yanagida, M. (1994) J. Cell Sci., 107, 1725-1735), our studies suggest that the ppb1+ gene plays a role in the gene expression cascade that is essential for mating and sporulation in S. pombe.

Amino Acid Sequence↗

The Autographa californica nuclear polyhedrosis virus homologous region 1a: identical sequences are essential for DNA replication activity and transcriptional enhancer function.

Hr1a consists of two 30-bp imperfect palindrome sequences separated by 58 bp and each palindrome contains a naturally occurring EcoRI site at its core. Plasmid subclones of the hr1a-containing AcMNPV HindIII-N fragment were examined for their ability to replicate in virus-infected (Spodoptera frugiperda) Sf9 cells, and to stimulate transcription when linked in cis with a 39K gene promoter-beta-glucuronidase fusion and cotransfected into cells along with a plasmid (ple-1) containing the gene encoding the trans-acting factor IE-1. Only those plasmids containing hr1a underwent infection-dependent replication and were able to stimulate transcription. Sequences mapping to the left of hr1a were required for maximal levels of replication. A single palindrome from hr1a was sufficient for supporting plasmid replication and for stimulating transcription, although both activities were more efficient when both palindromes were present. Plasmids containing only one-half of a palindrome or disruptions of the central EcoRI core either did not replicate, or replicated very poorly, and did not exhibit enhanced transcriptional activity from the 39K gene promoter. Gel retardation experiments showed that labeled hr1a-containing DNA fragments had retarded migration after incubation with extracts from cells transfected with ple-1. Supershift experiments using polyclonal antibodies to IE-1 indicated that IE-1 is a component of the protein complex bound to hr1a. Fragments containing disruptions of the EcoRI-core still bound IE-1, as shown by gel retardation assays, indicating that IE-1 binding alone is not sufficient to allow replication and transcriptional enhancement.

Animals↗

[Lumbar disk prolapse--who will recover first?].

This study was set up to show whether certain social and demographic characteristics play any significant role for the length of disease in patients with lumbar disc herniation. All patients operated upon during one year (n = 171), were included. Of these, 168 had been operated for the first time. Four dates were recorded: Onset of symptoms, referral to hospital, operation and recovery. They were grouped according to sex, age, domicile (town, rural area), employed/unemployed, socialclass and way of referral. The total period from onset of symptoms to recovery was significantly shorter for those who were employed as opposed to unemployed and even shorter with increasing socialclass. The period from onset of symptoms to referral was responsible for most of this difference. None of the factors sex, age or domicile were found to be related to outcome parameters. It is recommended that general practitioners are especially aware of the late referral of patients with lumbar disc herniation from the lower social groups.

Adolescent↗

First clinical experience with sonicated human serum albumin (Albunex) as an intrafallopian ultrasound contrast medium.

The safety and preliminary efficacy of a new ultrasound contrast medium. Albunex for evaluating Fallopian tube patency during transvaginal sonography were studied in seven women. All of the women had sought medical attention because of uterine fibroids and excessive menstrual bleeding and were scheduled for a subsequent hysterosalpingectomy 3 weeks after the ultrasound examination. Albunex was injected transcervically in doses ranging from 0.5 to 9 ml, alternating with saline, during concomitant transvaginal ultrasound scanning. There were no serious adverse reactions. Peroperative macroscopic and postoperative microscopic investigations of the endometrium. Fallopian tubes and peritoneal biopsies revealed no pathological changes. Agreement between hysterosalpingo contrast sonography (HyCoSy) and postoperative testing for the evaluation of tubal patency was observed in 12 out of 14 Fallopian tubes. These findings suggest that Albunex may safely be used as an intrafallopian contrast medium in ultrasound investigations.

Adult↗

Mutational analysis of the Prt1 protein subunit of yeast translation initiation factor 3.

The Saccharomyces cerevisiae PRT1 gene product Prt1p is a component of translation initiation factor eIF-3, and mutations in PRT1 inhibit translation initiation. We have investigated structural and functional aspects of Prt1p and its gene. Transcript analysis and deletion of the PRT1 5' end revealed that translation of PRT1 mRNA is probably initiated at the second in-frame ATG in the open reading frame. The amino acid changes encoded by six independent temperature-sensitive prt1 mutant alleles were found to be distributed throughout the central and C-terminal regions of Prt1p. The temperature sensitivity of each mutant allele was due to a single missense mutation, except for the prt1-2 allele, in which two missense mutations were required. In-frame deletion of an N-terminal region of Prt1p generated a novel, dominant-negative form of Prt1p that inhibits translation initiation even in the presence of wild-type Prt1p. Subcellular fractionation suggested that the dominant-negative Prt1p competes with wild-type Prt1p for association with a component of large Prt1p complexes and as a result inhibits the binding of wild-type Prt1p to the 40S ribosome.

Alleles↗

The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans.

The gene encoding the homologue of the catalytic subunit of the Ca2+/calmodulin-regulated protein phosphatase 2B (calcineurin A) has been isolated from Aspergillus nidulans. This gene, cnaA+, is essential in this fungal system. Analysis of growth-arrested cells following gene disruption by homologous recombination reveals that they are blocked early in the cell cycle. The cnaA+ gene encodes a 2.5 kb mRNA and the deduced protein sequence is highly homologous to the calcineurin A subunit of other species. The mRNA varies in a cell cycle-dependent manner with maximal levels found early in G1 and considerably before the G1/S boundary. As calmodulin is also essential for A. nidulans cell cycle progression and levels rise before the G1/S boundary, our data suggest that calcineurin may represent a primary target for calmodulin at this cell cycle transition point.

Amino Acid Sequence↗

The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans.

The gene encoding the homologue of the catalytic subunit of the Ca2+/calmodulin-regulated protein phosphatase 2B (calcineurin A) has been isolated from Aspergillus nidulans. This gene, cnaA+, is essential in this fungal system. Analysis of growth-arrested cells following gene disruption by homologous recombination reveals that they are blocked early in the cell cycle. The cnaA+ gene encodes a 2.5 kb mRNA and the deduced protein sequence is highly homologous to the calcineurin A subunit of other species. The mRNA varies in a cell cycle-dependent manner with maximal levels found early in G1 and considerably before the G1/S boundary. As calmodulin is also essential for A.nidulans cell cycle progression and levels rise before the G1/S boundary, our data suggest that calcineurin may represent a primary target for calmodulin at this cell cycle transition point.

Amino Acid Sequence↗

Thromboembolic prophylaxis with low molecular weight heparin during pregnancy.

OBJECTIVE: The objective of this study was to show that low molecular weight heparin (LMWH) can be used in preventing veno-pulmonary thromboembolic diseases in pregnancy. METHODS: Twenty-four women carrying 27 pregnancies with known risk of veno-pulmonary thromboembolic diseases in pregnancy were prophylactically treated with LMWH (dalteparin) during part of their pregnancy. Our therapeutic target was a plasma concentration of 0.20-0.50 anti-Xa U/ml measured 2-6 h after subcutaneous administration of LMWH into the abdominal wall. To obtain this anti-Xa activity the patients were given total doses of 2500-10,000 anti-Xa U daily. Monitoring of anti-Xa activity in patients receiving < or = 5000 U/day was not necessary. RESULTS: Twelve out of the 24 women received LMWH at the time of delivery. Our biochemical assay could not show the presence of anti-Xa activity in the blood samples from the babies although it was possible to show anti-Xa activity in their mothers. In three out of 24 women, blood samples showed activation of coagulation. These patients were changed to the vitamin K antagonist phenindione. CONCLUSIONS: None of the treated women showed any clinical or paraclinical signs of thromboembolic diseases during pregnancy or 6 weeks postpartum. All the babies were born healthy. None of the women had any side effects due to the treatment.

Factor Xa Inhibitors↗

Characterization of the Spodoptera frugiperda TATA-binding protein: nucleotide sequence and response to baculovirus infection.

A cDNA clone containing a 921 bp open-reading frame (307 amino acids; 34 kDa) homologous to the TATA-binding protein (TBP) was isolated and sequenced from a Spodoptera frugiperda cell line that is commonly used in the baculovirus expression system. Analysis of the S. frugiperda TBP (SfTBP) sequence showed that the amino-terminal portion of SfTBP diverged significantly from that of other TBP sequences including Drosophila melanogaster whereas the carboxy-terminal sequence was highly conserved. Southern blot analysis indicated that SfTBP was encoded by a single gene in the S. frugiperda genome. Northern blot analysis indicated that steady-state levels of the 1.3 kb SfTBP transcript declined by 24 h post-infection corresponding to the time of virus-induced inhibition of host-cell transcription. Corresponding western blot analysis showed that TBP protein levels remain constant up to 72 h post-infection.

Amino Acid Sequence↗

Inhibition of G2/M progression in Schizosaccharomyces pombe by a mutant calmodulin kinase II with constitutive activity.

Intracellular signaling by the second messenger Ca2+ through its receptor calmodulin (CaM) regulates cell function via the activation of CaM-dependent enzymes. Previous studies have shown that cell cycle progression at G1/S and G2/M is sensitive to intracellular CaM levels. However, little is known about the CaM-regulated enzymes involved. Protein phosphorylation has been shown to be important for cell-cycle regulation. Because CaM regulates several protein kinases, and at least one protein phosphatase, our studies are focusing on the roles of these enzymes within the cell cycle. As an initial approach to this problem, cDNAs encoding either normal or mutant calcium/calmodulin kinase II (CaMKII) have been expressed in Schizosaccharomyces pombe. The results show that overexpression of a constitutively active mutant CaMKII caused cell-cycle arrest in G2. Arrest was associated with a failure to activate the p34/cdc2 protein kinase. Expression of the mutant CaMKII in strains of S. pombe with altered timing of mitosis revealed that this effect is not mediated either by cdc25+ or wee1+, suggesting that CaMKII may regulate G2/M progression by another mechanism.

Animals↗

The optimal dosing regimen for citalopram--a meta-analysis of nine placebo-controlled studies.

Optimal dosing schedules for an antidepressant drug can only be established during clinical studies in depressed patients. The benefits of antidepressant therapy are usually progressive, and thus patients must be maintained on a particular treatment for at least 3-4 weeks to assess the efficacy of different doses. Meta-analysis, a widely accepted statistical technique which allows the combination of the results of multiple studies, was used to assess the efficacy of several doses of citalopram over nine placebo-controlled clinical trials. Statistically significant differences between citalopram and placebo were found at both the 20 and 40 mg dose levels. The minimal effective dose of citalopram was shown to be 20 mg. However, analysis of patient subgroups revealed a tendency for those patients suffering from severe or recurrent depression to achieve better results with a higher dosage (40 mg), while patients experiencing their first period of depression or with less severe depression responded well to the minimally effective dose of 20 mg.

Adolescent↗

A change in the isoforms of human chorionic gonadotropin occurs around the 13th week of gestation.

hCG exhibits a considerable heterogeneity in blood during pregnancy. The overall charge of the isoforms of hCG has been shown to be more negative in the early than in the latter part of pregnancy. The present study analyzes the change in median charge and the charge heterogeneity as pregnancy progresses. The hCG activity in sera from 76 women from weeks 6-43 of gestation was measured with a noncompetitive time-resolved sandwich fluoroimmunoassay. The median charge and degree of charge heterogeneity of the isoforms of hCG in each serum was determined by electrophoresis in 0.10% agarose suspension. Median charge was expressed as median electrophoretic mobility. Electrophoresis with a high resolution revealed that the number of isoforms of hCG in a serum specimen from week 36 of gestation was 20-30. A change in median charge was found to occur at a limited time period of gestation, around the 13th week. All 16 sera from weeks 6-10 had isoforms of hCG with a more negative median charge than that of hCG in 21 sera from weeks 16-43 of gestation. The change in charge was accompanied by an increased degree of charge heterogeneity. There was a significant (P < 0.01) correlation between median mobility and the concentration of hCG during weeks 11-15 of gestation, but not before or after this period. There was no relationship between the sex of the fetus and the median charge of the isoforms of hCG. The data show that a change in the isoforms of hCG, revealed by a change in median charge of hCG, occurs at a limited time around the 13th week of gestation. This change occurs when the hCG concentration in blood decreases, and the placental production of estradiol and progesterone rapidly increases.

Adult↗

Frequency of proximal tubal obstruction in patients undergoing infertility evaluation.

Fallopian tube recanalization is a technique for treatment of proximal tubal obstruction caused by debris. The true frequency of infertile women for whom this treatment is suitable is not well known. In this study all hysterosalpingograms (HSGs) performed over a 3-year period (1986-88) were reviewed. The HSGs were performed as part of an infertility evaluation program in 494 women, with a mean duration of infertility of 2.4 years. Bilateral proximal tubal obstruction was found in 3% and unilateral proximal obstruction in 2% of the cases. In women examined in the first 2 years (1986-87) (n = 328), the birth frequency after HSG was 25%. When HSG was performed with optimal technique the number of patients who were suitable for Fallopian tube recanalization was low.

Adult↗