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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 163 records · Page 9Linked to original sources
PubMed1993

Infections in patients treated with high-dose chemotherapy for germ cell tumours.

25 patients with disseminated germ cell tumours were treated with high-dose cisplatin and etoposide (40 mg/m2 and 200 mg/m2 daily x five, respectively) leading to severe myelosuppression. A comprehensive study was undertaken in order to identify and describe the bacterial, viral and fungal infections in this group of patients. Fever (> 38.5 degrees C) and leucopenia (white blood cell count < 1.0 x 10(9)/l) were observed in 61 of 90 treatment cycles (68%). A microbiological aetiology compatible with the clinical manifestations of infection could be identified in 33 of the 61 febrile episodes (54%). Bacteraemia occurred in 14 episodes in 12 patients. Eight episodes (57%) involved gram-positive aerobic bacteria.

Adult↗
PubMed1993

Activation of human phagocytes by Helicobacter pylori. A novel interaction with neutrophils and monocytes distinct from that of N-formylated oligopeptides.

Sonicate proteins from Helicobacter pylori activate human neutrophils and monocytes for chemotactic and oxidative burst responses. The molecular nature of this activity and its interaction with the phagocyte membrane is unknown. Cross-stimulation experiments were performed with human neutrophils and monocytes preincubated in H. pylori sonicate and subsequently stimulated with the established and characterised stimuli N-f-methionyl-leucyl-phenylalanine (fMLP), the complement split product C5a (in zymosan-activated serum, ZAS), and phorbol-myristate-acetate (PMA). Checkerboard experiments confirmed the sonicate to be truly chemotactic, whereas no chemokinetic activity was demonstrated. At high concentrations of sonicate (1 mg/ml), a depressed chemotactic and oxidative burst response was observed, whereas the viability was > 98%. At lower concentrations (0.01-0.1 mg/ml), only weak deactivation could be induced for monocytes, i.e. the cells had a normal function. With neutrophils, even low concentrations of sonicate depressed the oxidative burs responsiveness. However, the reduced activity was unrelated to the stimulus applied indicating that H. pylori protein(s) activate human neutrophils and monocytes by a membrane binding site distinct from that of previously described receptors.

Chemotaxis, Leukocyte↗
PubMed1993

Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis.

After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease the next day to < 0.050 x 10(9) l-1, and this complete agranulocytosis continued for 10 days. As no response was obtained after 1 week the dosage of filgrastim was increased to 10 micrograms kg-1 day-1 with immediate improvement. A rapid and pronounced leucocytosis developed with maximal value of neutrophil granulocytes (including immature forms) of 33.108 x 10(9) l-1 on day 12 after admission. The patient only had minor infectious complications during the neutropenic period. In conclusion, early treatment with filgrastim seems warranted in severe cases of clozapine-induced agranulocytosis. A dosage of 10 micrograms kg-1 day-1 can be recommended.

Adult↗
PubMed1993

Tetranectin: a novel secretory protein from human monocytes.

Tetranectin is a recently described human plasma protein, which is found in most secretory cells throughout the body, including neutrophils. We present evidence for the presence of tetranectin in human monocytes and macrophages as well, and that these cells upon adherence or weak stimulation release a 20 kDa protein identified as tetranectin by immunoblotting. The amount of tetranectin released is 3-18 ng/h/10(6) monocytes. The possible influence of tetranectin on cellular functions was tested in migration and oxidative metabolism assays. Monocyte spontaneous migration was significantly stimulated by preincubation with purified tetranectin, whereas chemotactic and chemiluminescence responses to fMLP and C5a were unchanged. Neutrophil functions were not affected. It is concluded that tetranectin is secreted from human mononuclear phagocytes upon weak stimulation, and that the secreted tetranectin facilities spontaneous migration of these cells.

Blood Proteins↗
PubMed1993

8-Methoxypsoralen DNA interstrand cross-linking of the ribosomal RNA genes in Tetrahymena thermophila. Distribution, repair and effect on rRNA synthesis.

The distribution and repair of 8-methoxypsoralen-DNA interstrand cross-links in the ribosomal RNA genes (rDNA) in Tetrahymena thermophila have been studied in vivo by Southern blot analysis. It is found that the cross-links at a density of < or = 1/2 x 10(4) base pairs (bp) are distributed equally between three domains (terminal spacer, transcribed region and central spacer) as defined by restriction enzyme analysis (BamHI and ClaI). It is furthermore shown that a dosage resulting in approximately one cross-link per rDNA molecule (21 kbp, two genes) is sufficient to block RNA synthesis. Finally, it is shown that the cross-links in the rDNA molecules are repaired at equal rate in all three domains within 24 h and that RNA synthesis is partly restored during this repair period. The majority of the cells also go through one to two cell divisions in this period but do not survive.

Animals↗
PubMed1993

Peptic ulcer: an infectious disease?

Since the ingestion studies by Marshall and Morris, Helicobacter pylori has been known to cause both acute and chronic infection in the human stomach activating both the cellular and the humoral immune system. It is of little or no value to evaluate the causative relationship of an infectious agent using Koch's criteria. The more recent criteria for causative relationships used in the science of epidemiology are more useful. These criteria include: (i) the characteristic of the association which is fulfilled for most cases of both duodenal and gastric ulcer; (ii) the temporal relationship which is fulfilled for duodenal ulcer and has not been investigated for gastric ulcer; (iii) the biological gradient which has been fulfilled for duodenal ulcer in a few studies but not investigated for gastric ulcer; (iv) the biological plausibility which is easily fulfilled for both duodenal and gastric ulcer; (v) the effect of an intervention which has been fulfilled for duodenal ulcer and in a few studies for gastric ulcer; and (vi) the coherence of these data with what is known about the disease which is fulfilled for both duodenal and gastric ulcer. Even though there is no need for all criteria to be fulfilled, further studies are necessary to confirm the temporal relationship between H. pylori and peptic ulcer, and the biological gradient of H. pylori in relation to the gastric ulcer. Even so, there is a strong indication that most of the peptic ulcers, apart from those caused by non-steroid anti-inflammatory drugs and Zollinger-Ellison-like syndromes, are caused by H. pylori infection.

Chronic Disease↗
PubMed1993

Survival and ultrastructural changes of Helicobacter pylori after phagocytosis by human polymorphonuclear leukocytes and monocytes.

Few studies have been carried out on the phagocytosis and killing of Helicobacter pylori by both polymorphonuclear leukocytes (PMNs) and monocytes. In this study, H. pylori was incubated for up to 60 min either alone or with phagocytes in the presence or absence of human serum. Both non-immune serum and immune serum were used. Reduction in the number of H. pylori, which corresponds to the killing of H. pylori, was analysed by a colony count and ultrastructural changes were studied by electron microscopy. No reduction in the number of H. pylori was found when the bacteria were incubated alone or with phagocytes in the absence of serum. It is remarkable that unopsonized H. pylori was phagocytosed. When immune serum was added to the suspensions of bacteria and phagocytes, the killing rate of H. pylori was found to depend on the ratio of H. pylori to phagocytes. Thus an excess of monocytes reduced the number of H. pylori, whereas an excess of PMNs resulted in complete killing of H. pylori. On incubation with PMNs and serum, ultrastructural changes were observed in the majority of the bacteria whether they were phagocytosed or not. Controls without serum did not show any changes in the morphology of H. pylori, indicating that components in the serum play an important role in the phagocytosis and killing of H. pylori. In contrast, several of the phagocytosed bacteria were found to be unaffected after incubation with monocytes and serum. Such preparations often contained large aggregates of platelets surrounding unaffected H. pylori. In the gastric mucosa, H. pylori is often found in excess as compared to the phagocytes. If these results can be compared to the situation in vivo, the phagocytes seem to be ineffective in the killing of H. pylori, and other immune mechanisms may therefore be of importance for the elimination of H. pylori from the gastric epithelium. The possible intracellular survival of H. pylori should be taken into account when treatment regimes for H. pylori infections are chosen.

Helicobacter pylori↗
PubMed1992

Structural organization of the genes encoding the small nuclear RNAs U1 to U6 of Tetrahymena thermophila is very similar to that of plant small nuclear RNA genes.

We report the sequences of the genes encoding the small nuclear RNAs (snRNAs) U1 to U6 of the ciliate Tetrahymena thermophila. The genes of the individual snRNAs exist in two to six slightly different copies per haploid genome. Sequence analyses of the gene-flanking regions indicate that there are two classes of snRNA genes. Both classes are characterized by several conserved sequence elements, some of which are unique to each class and some of which are found in both classes. Comparison of the promoter structure of the snRNA genes of T. thermophila with the promoter structures of snRNA genes of other organisms revealed several similarities to plant snRNA genes. These similarities include the overall promoter architecture as well as specific sequence elements. The structural organization of the 3' flanking region of some of the T. thermophila snRNA genes is not observed in other organisms. This finding is discussed in relation to a possible role in snRNA 3'-end formation.

Animals↗
PubMed1992

A novel class of nucleolar RNAs from Tetrahymena.

We describe a family of at least four nucleolar RNAs (snoRNAs) from the ciliate, Tetrahymena. The snoRNAs are 120-140 nucleotides long, moderately AU-rich and contain no modified nucleotides. Their 5' ends are blocked by a cap of unknown nature. The snoRNAs can be folded into similar secondary structures consisting of two hairpins separated by a single-stranded AU-rich spacer. The sequences and secondary structures show no extensive sequence or secondary structure resemblance to any other small RNAs in the public databases.

Animals↗
PubMed1992

[Angiofollicular lymph node hyperplasia (Castleman disease)].

Angiofollicular lymph node hyperplasia (Castleman's disease) is a relatively rare disease of differential diagnostic interest in patients with lymphadenopathy. The etiology and pathogenesis are still not elucidated. The disease is classified into localized and systemic types. The localized form is divided histologically into hyaline-vascular type and plasma cell types. The former is usually demonstrated incidentally as a widening of the mediastinum in otherwise asymptomatic patients. The plasma cell type usually presents in the abdominal lymph nodes and is accompanied by fever, loss of weight, anemia and hypergammaglobulinemia. Surgical treatment is curative in the localized disease. The systemic disease involves multiple lymph nodes, and multiple organs are affected. The prognosis is dubious, and frequently the patients rapidly die from septicemia or other infectious complications. Some patients develop malignancies. Treatment with glucocorticosteroids and chemotherapy has only demonstrated a limited effect. The diagnosis requires both a characteristic histopathology and typical clinical symptoms. A current illustrative case report is presented.

Castleman Disease↗
PubMed1992

Inheritance of the group I rDNA intron in Tetrahymena pigmentosa.

We have previously argued from phylogenetic sequence data that the group I intron in the rRNA genes of Tetrahymena was acquired by different Tetrahymena species at different times during evolution. We have now approached the question of intron mobility experimentally by crossing intron+ and intron- strains looking for a strong polarity in the inheritance of the intron (intron homing). Based on the genetic analysis we find that the intron in T. pigmentosa is inherited as a neutral character and that intron+ and intron- alleles segregate in a Mendelian fashion with no sign of intron homing. In an analysis of vegetatively growing cells containing intron+ and intron- rDNA, initially in the same macronucleus, we similarly find no evidence of intron homing. During the course of this work, we observed to our surprise that progeny clones from some crosses contained three types of rDNA. One possible explanation is that T. pigmentosa has two rdn loci in contrast to the single locus found in T. thermophila. Some of the progeny clones from the genetic analysis were expanded for several hundred generations, and allelic assortment of the rDNA was demonstrated by subcloning analysis.

Alleles↗
PubMed1992

Defective monocyte oxidative metabolism in a child with Smith-Lemli-Opitz syndrome.

We present a patient with Smith-Lemli-Opitz syndrome with immunodeficiency. The patient suffered numerous infectious episodes, atopic dermatitis and wheezing. Immunological investigations demonstrated severely reduced oxidative burst-responsiveness of the blood monocytes, whereas chemotaxis, phagocytosis and interleukin-1 production were normal. Tests of neutrophils and lymphocytes were normal excluding previously described immune deficiency disorders. The father proved to have diminished monocyte oxidative metabolism as well, whereas the mother had normal monocyte function. The genetic and immunological aspects are discussed in relation to the syndrome.

Abnormalities, Multiple↗
PubMed1992

Activation of human phagocyte oxidative metabolism by Helicobacter pylori.

A characteristic feature of chronic antral gastritis is the abundant inflammatory response in close association with Helicobacter pylori, but the immunopathological mechanisms of tissue damage are unknown. Because reactive oxygen radicals have been implicated in the tissue damage of other chronic inflammatory disorders, we investigated the potential ability of H. pylori sonicate to influence the oxidative burst responsiveness of human polymorphonuclear leukocytes and monocytes. For both cell types, a dose-dependent stimulation in a chemiluminescence system was observed. Furthermore, preincubation in sonicate caused a marked priming of the cells to subsequent stimulation with the oligopeptide N-f-methionyl-leucyl-phenylalanine and phorbol-myristate-acetate. The sonicate activity was nondialysable, completely destroyed by proteinase and resistant to heat treatment. However, dialysis of boiled sonicate significantly reduced the activity, suggesting the breakdown of a larger molecule(s) to smaller fragments still biologically active. Preliminary experiments suggest that the activity is 25-35 kilodaltons. The demonstration of a protein with stimulatory activity for production of reactive oxygen radicals by human phagocytes may contribute to the understanding of the immunopathology associated with H. pylori infection.

Adult↗