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Biomedical subjects

K B Jensen

Publications and source records attributed to K B Jensen.

At least 37 records · Page 2Linked to original sources

Increased amount of zinc in the hippocampus and amygdala of Alzheimer's diseased brains: a proton-induced X-ray emission spectroscopic analysis of cryostat sections from autopsy material.

Zinc has been implicated as a contributing cause of the neuropathology of Alzheimer's disease (AD), but consensus on the zinc content of AD brains has not yet been established. In the present study, multi-element PIXE was used to measure zinc in cryostat sections of brain tissue from AD patients and from normal control subjects. Compared to their age-matched controls, the AD patients showed an increase in zinc in the hippocampal and amygdalar regions. The instrumental PIXE assays do not show whether the zinc changes are due to altered zinc in the boutons of Zinc-ENriched (ZEN) neurons, i.e., zinc ions in synaptic vesicles, or to changes in the amount of zinc tightly bound to macromolecules. We hypothesise that the increased zinc level is caused by an increase in the amount of ZEN terminals. Such an increase could be the result of a sprout of ZEN terminals in diseased areas of the brain.

Aged↗

Distinct differences in partial oxygen pressure at micrometer ranges in the rat hippocampal region.

A mapping at micrometer ranges of the partial oxygen pressure in the rat hippocampus was performed. The oxygen tension in the rat hippocampal region was measured using a glass oxygen microsensor in 30-microm steps along straight lines at a set of stereotactic coordinates. In the hippocampus the pattern of the oxygen tensions reflected the autometallographic zinc sulphide (AMG(ZnS)) pattern, i.e. the pattern of zinc enriched (ZEN) terminals. The highest levels of oxygen tension were recorded in the areas that are most heavily stained with the autometallographic zinc sulphide (AMG(ZnS)) method, like hilus fasciae dentatae. The zinc ions located in synaptic vesicles of the ZEN terminals can also be demonstrated by AMG silver amplification in brains from animals in vivo treated with sodium selenite. This method depends on the presence of a substantial reduction capacity of the tissues as selenite ions (SeO(2)(3)-) must to be reduced to selenide ions (Se2-) before the catalytic zinc selenide crystals can be formed. At some point, either during the transport from the infusion site to the actual target tissue or in the target tissue itself, selenium is reduced from Se(+ IV) to Se(- II). The importance of the reduction capacity of the target tissue in this process is demonstrated by the fact that areas found to have the highest concentration of zinc ions, e.g. hilus fasciae dentatae and the mossy fibres of CA3, are almost unstained after 1 h of i.p. Na2SeO3 exposure. An explanation of this phenomenon could be that the reduction process Se(+ IV) <==> Se(- II) leading to the formation of Se2- is moved to the left by the presence of oxygen, thus inhibiting the precipitation of ZnSe crystals. It is suggested that the subtle oxygen pressure pattern found in the rat hippocampus might also reflect essential biological zinc-related mechanisms vital to brain function.

Animals↗

Using in vitro selection to direct the covalent attachment of human immunodeficiency virus type 1 Rev protein to high-affinity RNA ligands.

We have used an in vitro selection procedure called crosslinking SELEX (SELEX = systematic evolution of ligands by exponential enrichment) to identify RNA sequences that bind with high affinity and crosslink to the Rev protein from human immunodeficiency virus type 1 (HIV-1). A randomized RNA library substituted with the photoreactive chromophore 5-iodouracil was irradiated with monochromatic UV light in the presence of Rev. Those sequences with the ability to photocrosslink to Rev were partitioned from the rest of the RNA pool, amplified, and used for the next round of selection. Rounds of photocrosslinking selection were alternated with rounds of selection for RNA sequences with high affinity to Rev. This iterative, dual-selection method yielded RNA molecules with subnanomolar dissociation constants and high efficiency photocrosslinking to Rev. Some of the RNA molecules isolated by this procedure form a stable complex with Rev that is resistant to denaturing gel electrophoresis in the absence of UV irradiation. In vitro selection of nucleic acids by using modified nucleotides allows the isolation of nucleic acid molecules with potentially limitless chemical capacities to covalently attack a target molecule.

Base Sequence↗

Phylogenetic relationships of the monogenomic species of the wheat tribe, Triticeae (Poaceae), inferred from nuclear rDNA (internal transcribed spacer) sequences.

Phylogenetic relationships of 30 diploid species of Triticeae (Poaceae) representing 19 genomes were estimated from the sequences of the internal transcribed spacer (ITS) region of nuclear ribosomal DNA. The ITS sequence phylogeny indicated that: (i) each genome group of species is monophyletic, concordant with cytogenetic evidence; (ii) Hordeum (I) and Critesion (H) are basal; (iii) Australopyrum (W) is closely related to Agropyron (P); (iv) Peridictyon (G), Heteranthelium (Q), and Dasypyrum (V) are closely related to Pseudoroegneria (S); (v) most of the annuals, Triticum s.l. (A, B, D), Crithopsis (K), Taeniatherum (T), Eremopyrum (F), Henrardia (O), Secale (R), and two perennials, Thinopyrum (J) and Lophopyrum (E), all of Mediterranean origin, are a monophyletic group. However, phylogenetic trees based on morphology group these Mediteranean species with various perennial lineages of the Arctic-temperate region. The molecular data and biogeography of the tribe suggest that the Mediterranean lineage is derived from the Arctic-temperate lineage and that the two lineages have evolved in parallel. Extensive morphological parallelism apparently obscures the true genealogical history of the tribe when only morphology is considered.

Africa, Northern↗

Characterization of an in vitro-selected RNA ligand to the HIV-1 Rev protein.

A small RNA ligand with high affinity for the HIV-1 Rev protein, generated by the SELEX in vitro evolution method, was used in a series of chemical modification studies to aid in determining the secondary structure of the ligand, to detect which modifications interfere with the binding of the ligand to Rev, and to find those modifiable groups that are protected from attack when bound to the Rev protein. This SELEX RNA ligand, like the high-affinity binding site of the Rev-responsive element, seems to bind the Rev protein within or along the major groove. There are two major regions of the RNA that interact with the Rev protein, and these regions appear to be close in space. Additionally, this high-affinity ligand has been used as the basis for an additional "biased randomization" SELEX procedure, in an effort to gain comprehensive information on the RNA sequences and structural elements necessary for efficient binding to the Rev protein. This complementary experimental approach supports the structural conclusions of our chemical modification data.

Base Composition↗

Biosystematic study of hexaploids Elymus tschimganicus and E. glaucissimus. I. Morphology and genomic constitution.

Elymus tschimganicus and E. glaucissimus are hexaploids (2n = 6x = 42) that inhabit stony slopes and swales in the middle and upper mountain belts of Central Asia. Chromosome pairing at metaphase I in E. tschimganicus and E. glaucissimus was typical of other Elymus hexaploids, averaging 20.94 and 20.98 bivalents per cell, respectively. Meiotic pairing of tetraploid hybrids derived by crossing E. tschimganicus and E. glaucissimus with P. spicata (2n = 2x = 14; genome = SS) averaged 4.97 and 4.90 bivalents per cell respectively, indicating the presence of the S genome in the target taxa. Pentaploid hybrids derived by crossing E. tschimganicus and E. glaucissimus with tetraploid analyzer species E. mutabilis and E. sibiricus (2n = 4x = 28; genome = SSHH) had mean bivalent frequencies of 5.61 and 4.64 respectively, suggesting the absence of the H genome in the target taxa. Mean bivalent associations were similar among hybrids derived by crossing the target taxa with E. nevski (2n = 4x = 28; genome = SSYY), which averaged 10.61 and 11.42 bivalents, respectively, suggesting the presence of the Y genome in E. tschimganicus and E. glaucissimus. Based on chromosome pairing in the hybrids, the genomic formula for both E. tschimganicus and E. glaucissimus should be SSSSYY.

Chimera↗

Phylogenetic relationships of 10 grass species: an assessment of phylogenetic utility of the internal transcribed spacer region in nuclear ribosomal DNA in monocots.

Entire sequences of the internal transcribed spacers (ITSs) and 5.8S subunit of nuclear ribosomal DNA (nrDNA) were obtained from nine grass species by direct double-stranded sequencing of polymerase chain reaction (PCR) amplified DNA fragments. These sequences from subfamily Pooideae (Triticum aestivum, Crithodium monococcum, Sitopsis speltoides, Hordeum vulgare, Secale montanum, Avena longiglumis, Bromus inermis, Brachypodium distachyon) and subfamily Panicoideae (Sorghum bicolor) together with published ITS sequence of rice (Oryza sativa, Bambusoideae) were analyzed using Wagner parsimony (PAUP) and the neighbor-joining distance method to assess the phylogenetic utility of ITS sequences at various taxonomic levels. Among the aligned sequences that ranged from 588 to 603 nucleotides in length, 118 of 269 variable sites contained potential phylogenetic information. A member of Bromus, B. inermis, was the sister taxon to the Triticeae species. Brachypodium was more distantly related to Triticeae than was Bromus or Avena. These data, with Oryza sativa as the outgroup, indicate monophyly of the Pooideae species and of the members of the tribe Triticeae within Pooideae. Phylogenetic trees of the 10 grass species generated from the ITS sequence data were in general agreement with phylogenies based on molecular data from ribosomal RNA (rRNA) and chloroplast DNA (cpDNA) of similar grass taxa. This study reaffirms that sequences of the ITS region are useful for phylogenetic inference among closely related monocot species.

Base Sequence↗

Drug related admissions to medical wards: a population based survey.

1. In total 1999 consecutive admissions to six medical wards were subjected to a prospective high-intensity drug event monitoring scheme to assess the extent and pattern of admissions caused by adverse drug reactions (ADRs) or dose related therapeutic failures (TF), in a population-based design. The wards were sub-specialised in general medicine, geriatrics, endocrinology, cardiology, respiratory medicine and gastroenterology. 2. Considering definite, probable and possible drug events, the prevalence of drug related hospital admissions was 11.4% of which 8.4% were caused by ADRs and 3.0% by TFs. There were large inter-department differences. 3. The six classes of drugs most frequently involved in admissions caused by ADRs were anti-rheumatics and analgesics (27%), cardiovascular drugs (23%), psychotropic drugs (14%), anti-diabetics (12%), antibiotics (7%), and corticosteroids (5%). Noncompliance accounted for 66% of the TFs with diuretics and anti-asthmatics most frequently involved. 4. The pattern of drugs involved in ADRs was compared with the regional drug sales statistics. Drugs with a particularly high rate of ADR related admissions per unit dispensed were nitrofurantoin and insulin (617 and 182 admissions per 1,000,000 defined daily doses), while low rates were seen for diuretics and benzodiazepines (10 and 7 admissions per 1,000,000 defined daily doses). Confidence intervals were wide. 5. Patients who had their therapy prescribed by a hospital doctor had a slightly higher prevalence of drug events than those who were treated by a general practitioner (12.6% vs 11.8%). The reverse applied for drug events assessed as avoidable (3.3% vs 4.6%). Although these differences were not statistically significant, it may suggest general practitioners as the appropriate target for interventive measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Aberrations of chromosome 6 in 193 newly diagnosed untreated cases of chronic lymphocytic leukemia.

Aberrations of chromosome 6 were observed in 11 of 193 cases of chronic lymphocytic leukemia diagnosed January 1, 1984-November 1, 1988 and investigated cytogenetically within 30 days after diagnosis. The 6p was rearranged in 5 cases: 4 balanced and 1 unbalanced translocation. The 6q was involved in 6 cases: 4 deletions and 2 balanced translocations. Three of the del(6q) may be identical: del(6)(q13q27). In two cases there were no additional aberrations. Aberrations of chromosome 6 correlated significantly with an advanced clinical stage, diffuse pattern of bone marrow infiltration, and increased SmIgM-fluorescence intensity. All these factors are associated with poor prognosis. Although the number of cases with 6q aberrations is still too small and the observation period too short to show significant influence on survival, the presence of 6q aberrations at diagnosis may prove useful in delineating a subtype of chronic lymphocytic leukemia with poor prognosis.

Bone Marrow↗

Drug-related admissions to a department of medical gastroenterology. The role of self-medicated and prescribed drugs.

Three hundred and twenty-eight consecutive patients admitted to a department of medical gastroenterology were evaluated in a high-intensity study of drug-related hospitalizations (DRH). The drug events considered were adverse drug reaction and dose-related therapeutic failures (DTF). With regards to the 'definite' and 'probable' drug events, DRHs accounted for 26 admissions (7.9%; 95% confidence interval (CI), 5.2-11.4%), and with the additional inclusion of 'possible' drug events DRHs accounted for 39 admissions (11.9%; CI, 8.6-15.9%). Of these, five and seven admissions, respectively, were caused by DTF. Patients admitted because of drug events took significantly more drugs than others. An evaluation of the circumstances of the 26 'definite' or 'probable' DRH showed none to be 'definitely avoidable', 6 to be 'possibly avoidable', and 20 to be 'not avoidable' by efforts from the prescribing physicians. Gastroduodenal lesions causally related to non-steroidal anti-inflammatory drug (NSAID) or aspirin use accounted for 17 of the definite, probable, or possible DRHs (44%). Only 1 of the 11 cases related to NSAID use was rated as possibly avoidable by efforts from the health service personnel. In 13 cases self-medication with aspirin played a substantial role in the DRH. Self-medication was largely characterized by poor indication, uncontrolled use, polypharmacy, treatment of epigastric pain with aspirin, and the patient's unawareness of potential adverse reactions. This suggests the need for intensified information to the public concerning the adverse effects of aspirin and NSAID.

Adult↗

Aclarubicin plus cytosine arabinoside versus daunorubicin plus cytosine arabinoside in previously untreated patients with acute myeloid leukemia: a Danish national phase III trial. The Danish Society of Hematology Study Group on AML, Denmark.

A regimen of aclarubicin (ACR) of 75 mg/m2 daily for 3 days plus a continuous intravenous infusion of cytosine arabinoside (ara-C) of 100 mg/m2 per day for 7 days was compared with daunorubicin (DNR) 45 mg/m2/day for 3 days plus ara-C for 7 days as first-line chemotherapy of de novo acute myeloid leukemia (AML) in a randomized, nationwide Danish study. A total of 180 patients aged between 17 and 65 years were entered onto the protocol. Patients who achieved complete remission (CR) were given five courses of intensive consolidation therapy consisting of two courses of high dose ara-C, two courses of amsacrine plus etoposide, and one course of DNR plus ara-C. Of 174 evaluable patients, 99 achieved CR. The rate of CR was significantly higher on ACR plus ara-C than on DNR plus ara-C [66% versus 50% (p = 0.043)] and decreased significantly with increasing age. The hematological toxicity was identical for the two regimens. A total of 83 patients entered consolidation therapy. At 4 years, 37% of patients with CR following ACR were still in remission compared with 33% following DNR (p = 0.48), and the total survival at 4 years was 29% versus 20% (p = 0.26). The duration of remission and total survival both decreased with increasing age. ACR plus ara-C seem at least as good or better than DNR plus ara-C as first-line chemotherapy of AML.

Aclarubicin↗

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial.

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p less than 0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine. This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.

Adolescent↗