Search PubMed⌕ Search

Biomedical subjects

I Kramer

Publications and source records attributed to I Kramer.

At least 19 recordsLinked to original sources

HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping.

Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13.0% (0%) C282Y homozygotes, 5.8% (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The values for 420 Danish blood donors are shown in parentheses. The distribution of genotypes in group B was similar to that of the blood donors. Serum ferritin, transferrin iron saturation and pathological data were collected from 38 randomly selected C282Y homozygotes, 36 H63D/C282Y compound heterozygotes, 19 H63D heterozygotes, 17 S65C heterozygotes and 144 wild-types. All of the C282Y homozygotes and 28% of the compound heterozygotes were diagnosed as HH patients. There was no evidence of HH in the H63D homozygotes or S65C heterozygotes. Moreover, 7 wild-type patients, 2 C282Y heterozygote patients and one H63D heterozygote patient fulfilled the criteria for HH. The significant enrichment of HH among associated genotype samples submitted for HFE testing indicates that the clinical selection is generally adequate. However, the study showed substantial deviation in the selection efficiency among the various hospitals and general practitioners.

Blood Donors↗

Microbial diversity of cultivatable bacteria associated with the North Sea bryozoan Flustra foliacea.

The microbial diversity of cultivatable bacteria associated with the bryozoan species Flustra foliacea from the North Sea was investigated by a molecular approach. Amplified ribosomal RNA restriction analyses (ARDRA) and 16S rDNA partial sequence analysis revealed differences in the composition of cultivatable bacteria populations from single bryozoan colonies collected from two different sampling sites in the North Sea as well from one site taken at different points in time. Whereas gamma-Proteobacteria identified as Shewanella frigidimarina, Pseudoalteromonas ssp. and Psycbrobacter ssp. were predominant on samples of Flustra I (taken near the island of Helgoland), most bacteria isolated from Flustra II, originating from the Steingrund, could be affiliated to Gram-positive taxa. Survey of the bryozoan samples from the latter site in February 2000 led to the detection of a phylogenetically mixed bacterial population, consisting of gamma-, and alpha-Proteobacteria and Gram-positive bacteria with low and high GC-content (Flustra III). As these bacteria are among the most widely isolated organisms from the marine environment, it may be concluded that the bryozoan Flustra foliacea accepts colonization of surfaces by bacteria which are common inhabitants of the marine environment and which may have been transferred into this environment from terrestrial sites.

Animals↗

Pelczaria aurantia ATCC 49321T (=DSM 12801T) is a strain of Kocuria rosea (Flügge 1886) Stackebrandt et al. 1995.

Phylogenetic and chemotaxonomic analyses of Pelczaria aurantia ATCC 49321T (= DSM 12801T) indicate that this species is very closely related to Kocuria rosea. The DNA-DNA reassociation value of 87.1% determined for the type strains of the two species supports this finding. The results of phylogenetic analysis of the 16S rDNA of a subculture of the original strain of Pelczaria aurantia, deposited at the National Institutes of Health, Bethesda, MD, USA, as 'Neisseria aurantia', are identical to those for strain ATCC 49321T and indicate that Pelczaria aurantia ATCC 49321T is an authentic subculture of the original culture described by Poston (1993). On the basis of these findings it is concluded that P. aurantia ATCC 49321T and K. rosea DSM 20447T are members of the same taxon. The taxonomic consequences of this union are discussed.

DNA, Bacterial↗

Sustained elevated levels of VCAM-1 in cultured fibroblast-like synoviocytes can be achieved by TNF-alpha in combination with either IL-4 or IL-13 through increased mRNA stability.

Rheumatoid arthritis is characterized by hyperplasia of the synovial lining and invasion of cartilage and bone by a subset of resident synovial cells named fibroblast-like synoviocytes. They are characterized by elevated expression of the vascular cell adhesion molecule-1 (VCAM-1). The intensity of VCAM-1 expression correlates with the degree of inflammation of the synovial joint. Differential VCAM-1 expression may determine inflammatory cell accumulation through its interaction with leukocytes that express the counterreceptor integrins alpha4beta1 and alpha4beta7. Elevated levels of VCAM-1 expression are thought to be a consequence of the presence of inflammatory mediators, in particular IL-1beta and TNF-alpha. Fibroblast-like synoviocytes rapidly up-regulate VCAM-1 expression in response to IL-1beta and TNF-alpha, but also to IL-4. However, we now show that the response to IL-1beta or TNF-alpha is of a brief transient nature, even when applied continuously over a period of 12 days, whereas the response to IL-4 or IL-13 is sustained. Great synergy is obtained by combining either IL-4 or IL-13 with TNF-alpha, which results in a highly elevated but also sustained expression of VCAM-1. The mechanism by which IL-4 or IL-13 prolongs VCAM-1 expression can be explained by a dramatic increase in the half-life of VCAM-1 mRNA.

Arthritis, Rheumatoid↗

Phylogenetic analysis of Formivibrio citricus, Propionivibrio dicarboxylicus, Anaerobiospirillum thomasii, Succinimonas amylolytica and Succinivibrio dextrinosolvens and proposal of Succinivibrionaceae fam. nov.

The phylogenetic position of Gram-negative, strictly anaerobic, non-spore-forming bacteria, representing four different genera, was determined by analysis of their 16S rDNA sequences. Formivibrio citricus and Propionivibrio dicarboxylicus are members of the beta-subclass of the class Proteobacteria. While Formivibrio citricus stands phylogenetically isolated, Propionivibrio dicarboxylicus is moderately related to members of the genus Rhodocyclus. Succinimonas amylolytica and Succinivibrio dextrinosolvens are members of the gamma-subclass of the class Proteobacteria in which they, together with members of the genus Anaerobiospirillum and Ruminobacter amylophilus, form a separate line of descent. This phylogenetic group is described as Succinivibrionaceae fam. nov.

DNA, Bacterial↗

Ornithinicoccus hortensis gen. nov., sp. nov., a soil actinomycete which contains L-ornithine.

Two Gram-positive coccoid, non-motile bacteria with L-ornithine as diagnostic diamino acid of the peptidoglycan and an interpeptide bridge of L-Orn<--Gly(1,2)<--D-Glu were isolated from a sample of garden soil. The major menaquinone is MK-8(H4). 13-methyl and 12-methyl tetradecanoic acids are the predominant fatty acids. The polar lipids are phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylserine and two unknown phospholipids. Mycolic acids are absent. The DNA base composition is 72 mol% G + C. Recent comparative 16S rDNA studies revealed that strains HKI 0125T and HKI 0131 represent a novel lineage adjacent to the family Intrasporangiaceae of the order Actinomycetales but distinct from the previously described genera of this family. On the basis of the genotypic, chemotaxonomic, morphological and physiological characteristics of these two isolates it is proposed to classify HKI 0125T and HKI 0131 in a new genus and species for which the name Ornithinicoccus hortensis gen. nov., sp. nov. is proposed. The type strain is HKI 0125T (= DSM 12335T).

Actinomycetales↗

Beutenbergia cavernae gen. nov., sp. nov., an L-lysine-containing actinomycete isolated from a cave.

Two aerobic, Gram-positive bacteria, strains HKI 0122T and HKI 0132, were isolated from a cave. Cells are not acid-fast, non-motile, non-spore-forming and exhibit a rod-coccus growth cycle. The cell wall peptidoglycan contains lysine in position 3 of the peptide subunit and an interpeptide bridge of L-Lys<--L-Glu. The major menaquinone is MK-8(H4), 13-methyl and 12-methyl tetradecanoic acids are the predominating fatty acids. The polar lipids consist of phosphatidylinositol, diphosphatidylglycerol and three unknown phospholipids. Mycolic acids are absent. The DNA base composition is 71 mol% G + C. Phylogenetic analysis revealed that strain HKI 0122T forms a novel taxon among the families and unassigned genera of the suborder Micrococcineae, within the order Actinomycetales. On the basis of the genotypic, chemotaxonomic, morphological and physiological characteristics of these two isolates it is proposed to assign strains HKI 0122T and HKI 0132 to a new genus and species for which the name Beutenbergia cavernae gen. nov., sp. nov. is proposed. The type strain is HKI 0122T (= DSM 12333T).

Actinomycetales↗

Phylogenetic basis for a taxonomic dissection of the genus Clostridium.

The 16S rDNA-based phylogenetic analysis of the genus Clostridium has been completed by determination of the phylogenetic position of the type strains of 15 species and two non-validated species. These strains are members of phylogenetic clusters I, III, IV, V, IX, XIVa and XVIII as defined previously by Collins et al. [Int. J. Syst. Bacteriol. 44 (1994) 812-826]. Members of the genus Clostridium span a large evolutionary distance and the genus is not a phylogenetically coherent taxon but is intermixed with members of different genera, exhibiting a combination of Clostridium- and non-Clostridium-type properties. Anaerobacter polyendosporus, Syntrophococcus sucromutans and Acetivibrio multivorans also cluster within the radiation of Clostridium species. Although several taxa have been described for former Clostridium species with distinct phenotypic properties, the majority of Clostridium species, which are not members of the core cluster I, can at present not be reclassified as long as taxon-specific, phenotypic properties are not available.

Base Sequence↗

Polynucleotide probes that target a hypervariable region of 16S rRNA genes to identify bacterial isolates corresponding to bands of community fingerprints.

Temperature gradient gel electrophoresis (TGGE) is well suited for fingerprinting bacterial communities by separating PCR-amplified fragments of 16S rRNA genes (16S ribosomal DNA [rDNA]). A strategy was developed and was generally applicable for linking 16S rDNA from community fingerprints to pure culture isolates from the same habitat. For this, digoxigenin-labeled polynucleotide probes were generated by PCR, using bands excised from TGGE community fingerprints as a template, and applied in hybridizations with dot blotted 16S rDNA amplified from bacterial isolates. Within 16S rDNA, the hypervariable V6 region, corresponding to positions 984 to 1047 (Escherichia coli 16S rDNA sequence), which is a subset of the region used for TGGE (positions 968 to 1401), best met the criteria of high phylogenetic variability, required for sufficient probe specificity, and closely flanking conserved priming sites for amplification. Removal of flanking conserved bases was necessary to enable the differentiation of closely related species. This was achieved by 5' exonuclease digestion, terminated by phosphorothioate bonds which were synthesized into the primers. The remaining complementary strand was removed by single-strand-specific digestion. Standard hybridization with truncated probes allowed differentiation of bacteria which differed by only two bases within the probe target site and 1.2% within the complete 16S rDNA. However, a truncated probe, derived from an excised TGGE band of a rhizosphere community, hybridized with three phylogenetically related isolates with identical V6 sequences. Only one of the isolates comigrated with the excised band in TGGE, which was shown to be due to identical sequences, demonstrating the utility of a combined TGGE and V6 probe approach.

Actinobacillus↗

p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase/PKB, mediated signaling pathways in T lymphocytes.

p21ras is activated by the T cell antigen receptor (TCR) and then co-ordinates important signaling pathways for T lymphocyte activation. Effector pathways for this guanine nucleotide binding protein in T cells are mediated by the serine/threonine kinase Raf-1 and the Ras-related GTPase Rac-1. In fibroblasts, an important effector for the Ras oncogene is Phosphatidylinositol 3-kinase (PtdIns 3-kinase). Activation of this lipid kinase is able to induce critical Rac-1 signaling pathways and can couple p21ras to cell survival mechanisms via the serine/threonine kinase Akt/PKB. The role of PtdIns 3-kinase in Ras signaling in T cells has not been explored. In the present study, we examined the ability of PtdIns 3-kinase to initiate the Rac-1 signaling pathways important for T cell activation. We also examined the possibility that Akt/PKB is regulated by Ras signaling pathways in T lymphocytes. The results show that Ras can initiate a Rac-1 mediated pathway that regulates the transcriptional function of AP-1 complexes. PtdIns 3-kinase signals cannot mimic p21ras and induce the Rac mediated responses of AP-1 transcriptional activation. Moreover, neither TCR or Ras activation of AP-1 is dependent on PtdIns 3-kinase. PKB is activated in response to triggering of the T cell antigen receptor; PtdIns 3-kinase activity is both required and sufficient for this TCR response. In contrast, p21ras signals are unable to induce Akt/PKB activity in T cell nor is Ras function required for Akt/PKB activation in response to the TCR. The present data thus highlight that PtdIns 3-kinase and Akt/PKB are not universal Ras effector molecules. Ras can initiate Rac-1 regulated signaling pathways in the context of T cell antigen receptor function independently of PtdIns 3-kinase activity.

Calcium-Calmodulin-Dependent Protein Kinases↗

NCAM 180 in the postnatal development of cat visual cortex: an immunohistochemical study.

The neural cell adhesion molecule (NCAM) consists of three major isoforms with differing extents of intracellular domains. The largest, NCAM 180, may play an important role in the development and stabilization of cell contacts because of its interaction with the cytoskeleton, its accumulation at contact sites between cells, and age-dependent modifications of the immunoreactivity of its intracellular domain. The developmental expression pattern of NCAM 180 was examined in the cat visual cortex to explore its relation with the age-dependent decline of synaptic malleability. Western blot and immunohistochemical analyses were carried out by using a monoclonal antibody (D3) directed against an epitope of the intracellular domain specific to NCAM 180 and antibodies against all NCAM isoforms. The latter revealed a similar time course of increased expression during development by both Western blot and immunohistochemical analysis. In contrast, the D3 antibody showed an age-dependent increase of immunoreactivity by Western blot analysis and a decrease of reactivity by immunohistochemistry. In addition, the D3 antibody revealed characteristic developmental changes of immunoreactivity in the neuropil and distribution of immunopositive neuronal cell bodies in the different cortical laminae. The observations from this and another study (Kramer et al., 1997) suggest that the D3 antibody-specific NCAM 180 epitope is masked during the stabilization of connectivity.

Animals↗

Developmentally regulated masking of an intracellular epitope of the 180 kDa isoform of the neural cell adhesion molecule NCAM.

The neural cell adhesion molecule NCAM is a cell surface glycoprotein that occurs in several isoforms. It was previously shown that the largest 180-kDa isoform of NCAM (NCAM 180) accumulates at sites of cell contact and in postsynaptic densities and may be responsible for the stabilization of cell contacts by its interaction with the membrane-cytoskeleton linker protein brain spectrin. In immunohistochemical studies on the expression of the NCAM 180, we noticed that two NCAM 180 specific monoclonal antibodies, termed 481 and D3, showed different patterns of immunoreactivity in sections of fresh-frozen adult mouse brain. Here we show that the D3-specific, but not the 481-specific epitope becomes inaccessible to the antibody during development of the hippocampal formation, coincident with the establishment of stable cell-cell contacts. In contrast, in the olfactory bulb with its continually regenerating olfactory nerve fibers, both NCAM 180 antibodies remain fully immunoreactive throughout development and adulthood. We also show that the D3-specific epitope becomes inaccessible in primary cerebellar neuron cultures with time in culture. Electrophoretic separation of hippocampal membrane proteins under nondenaturating conditions showed NCAM to be present in protein complexes of different molecular weights at different developmental stages. We propose that NCAM is involved in the formation of developmentally regulated, noncovalent complexes with as yet unknown partner molecules that could be responsible for the masking of the D3-specific epitope.

Animals↗

Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects.

Only in the past decade has a role of heredity in substance abuse been established as a result of extensive twin and family studies. More recently, several candidate genes have been investigated for their possible role in alcoholism and cocaine abuse. Specific genetic factors in opioid substance abuse have not been investigated in man, although animal studies suggest that quantitative trait loci (QTLs) can be identified that predispose mice both to morphine and alcohol preference. Central dopaminergic pathways figure prominently in drug-mediated reinforcement suggesting that dopamine receptors are likely candiadates for association with substance abuse in man. In addition, we recently reported an association between a human personality trait, Novelty Seeking and the long alleles (represented chiefly by the 7-repeat) of the D4 dopamine receptor (D4DR) exon III polymorphism. The personality trait of Novelty Seeking is also more pronounced in substance abusers, who score higher in this dimension than control subjects. The twin role of dopamine receptors in mediating Novelty Seeking and drugreinforcement prompted us to examine a group of Israeli heroin addicts for prevalence of the D4DR repeat polymorphism. We now show that the 7-repeat allele is significantly over-represented in the opioid-dependent cohort and confers a relative risk of 2.46. To our knowledge this is the first report of an association between a specific genetic polymorphism and opioid addiction.

Adult↗

Influence of short-term dietary measures on dioxin concentrations in human milk.

Breast-feeding may expose infants to high levels of toxic chlorinated dioxins. To diminish intake of these lipophilic compounds by the baby, two diets were tested for their ability to reduce concentrations of dioxins in human milk. The diets were a low-fat/high- carbohydrate/low-dioxin diet. (about 20% of energy intake derived from fat) and a high fat /low-carbohydrate/low-dioxin diet. These diets were tested in 16 and 18 breast-feeding women, respectively. The test diets were followed for 5 consecutive days in the fourth week after delivery. Milk was sampled before and at the end of the dietary regimen, and dioxin concentrations and fatty acid concentrations were determined. Despite significant influences of these diets on the fatty acid profiles, no significant influence on the dioxin concentrations in breast milk could be found. We conclude that short-term dietary measures will not reduce dioxin concentration in human milk.

Adult↗

Otitis media.

Explore the source record for details and available documents.

Child↗

T cell receptor/CD3 and CD28 use distinct intracellular signaling pathways.

Ligation of the T cell membrane antigen CD28 strongly enhances cytokine secretion in human T lymphocytes that are activated via T cell receptor (TcR)/CD3 or CD2 molecules. This study was undertaken to investigate whether, as has been indicated for activation via TcR/CD3, stimulation via CD28 is dependent on the activation of protein kinase C (PKC). Two inhibitors of PKC, 1-alkyl 2-methyl-glycerol and staurosporine, caused a dose-dependent inhibition of T cell proliferation induced by anti-CD3 monoclonal antibodies (mAb). The induction of interleukin (IL) 2 secretion was found to be more sensitive to the effects of the PKC inhibitors than the up-regulation of IL 2 receptor expression. In marked contrast, the anti-CD28 mAb-mediated enhancement of T cell proliferation and IL 2 secretion were insensitive to the action of either compound. We conclude that two independent signaling pathways may be operational in human T cells. The first used by TcR/CD3 depends on the activation of PKC, whereas the second is employed by CD28 and functions independently of PKC.

Alkaloids↗

[Physical characteristics of endometric instruments].

A method for measuring and documentation of the physical characteristics of electronic root canal length determination instruments is presented and illustrated by evaluation of ten different devices. Important parameters such as the influence of the capacitive component in alternating current resistances are presented by means of impedance-charts. All devices examined worked with alternating current; regarding frequency, signal form and resistances, which the devices interpreted as "Apex", the measurements obtained varied. The advantages of this method for clinical and experimental studies are discussed by the author.

Dental Instruments↗