Biomedical subjects

T Christensen

Publications and source records attributed to T Christensen.

At least 37 records · Page 2Linked to original sources

PubMed2001

Structural brain abnormalities in unselected in-patients with major depression.

OBJECTIVE: Several studies have indicated an increased frequency of cerebral atrophy and white matter lesions in patients with major depression, especially in older age groups. METHOD: Forty-four representative in-patients with major depression in which neurological disorders were clinically excluded, and 49 age- and gender-matched controls were MR scanned. RESULTS: Unexpectedly, two of the patients had severe brain pathology which could account for their psychiatric symptoms. Analysis of the remaining patients (mean age 42 years) did not reveal an increased frequency of cerebral atrophy. The number of white matter lesions increased with age to an odds ratio greater than 3 for patients aged 50, but this was not statistically significant. CONCLUSION: Brain atrophy and white matter lesions did not occur with significantly increased frequency in these relatively young unselected depressives, but the finding of severe brain pathology stresses the importance of brain imaging in late-onset psychiatric disorders.

Adult↗

PubMed2001

Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload.

The aim of the present study was to investigate the relationship between different measures of iron status, and the expression of CD2, and the activation markers CD25, CD71, CD45RO, HLADR CD38 within the Th-cell subset in patients with progressive transfusional iron overload. We estimated the expression of the activation surface markers on the Th cells of peripheral blood by flow cytometry from 22 multiply transfused patients. The number of CD2 binding sites (BS) on Th cells was significantly higher in the patients (82 917 +/- 30 801) than in age-matched normal controls (41 145 +/- 6989, P < 0.0001). When investigating whether this difference could be due to the iron overload we found the number of CD2 BS closely related to the iron saturation of serum transferrin (TfS) (R2 = 0.78, P < 0.001). The relationship to the serum ferritin concentration and to the number of blood units given was weaker, but also significant (R2 = 0.22, P < 0.027, respectively, R2 = 0.21, P < 0.032). Also the fraction of mature memory Th cells which express CD45RO at a high level was directly related to the TfS (R2 = 0.57, P < 0.0001), while the expression of CD38 within the Th cell fraction was inversely related to the TfS (R2 = - 0.43, P = 0.009). The expression of HLA-DR (but not of CD25 and CD71) was also directly related to the TfS (R2 = 0.29, P = 0.01). Our results show a clear, statistical relationship between the iron status and the expression of surface markers within Th cells in multiply transfused patients.

ADP-ribosyl Cyclase↗

PubMed2001

A simulation study of the reliability of recombination detection methods.

There exist many methods to detect recombination or mosaic structure in a sample of DNA sequences. But how reliable are they? Four methods were investigated with respect to their power to detect recombination in simulated samples with different amounts of recombination and mutation. In addition, we investigated the impact of the shape of the underlying genealogy on their performances. We found that the methods detected far fewer recombinations than were theoretically possible and that methods based on the principle of incompatibility in general had more power than methods that did not make use of this principle explicitly. This seemed, in particular, to be the case for phylogenies generated under population expansion scenarios which result in long branches at the tips and small deep branches. In addition to the results obtained through simulations, a series of new theoretical results on recombination is presented.

Algorithms↗

PubMed2001

The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33.

Cholecystokinin (CCK) occurs in multiple molecular forms; the major ones are CCK-58, -33, -22, and -8. Their relative abundance in human plasma and intestine, however, is debated. To settle the issue, extracts of intestinal biopsies and plasma from 10 human subjects have been examined by chromatography, enzyme cleavages, and measurements using a library of sequence-specific RIAs. Plasma samples were drawn in the fasting state and at intervals after a meal. The abundance of the larger forms varied with the 8 C-terminal assays in the library, as 2 assays overestimated and 3 underestimated the amounts present. One assay, however, measured carboxyamidated and O:-sulfated CCKs with equimolar potency before and after tryptic cleavage. This assay showed that the predominant plasma form is CCK-33, both in the fasting state ( approximately 51%) and postprandially ( approximately 57%), whereas CCK-22 is the second most abundant ( approximately 34% and 30%, respectively). In contrast, CCK-58 is less abundant in human intestines ( approximately 18%) and plasma ( approximately 11%). Its predominance in feline intestines, however, was confirmed. Hence, the results show a significant species variation and emphasize the necessity of highly specific and well characterized assays in molecular studies of CCK.

Animals↗

PubMed2001

The occurrence of sinusitis in HIV-infected patients with fever.

Sinusitis is commonly occurring in patients infected with Human Immunodeficiency Virus I (HIV), but the occurrence and etiology have not been established. The purpose of this study was prospectively to determine the occurrence, site and type of paranasal sinus abnormalities seen on MRI in HIV-infected patients with fever, to relate the abnormalities to clinical and immunological parameters, and to determine the microbiological agents found in the sinus aspirates. MRI was performed in 54 HIV-infected patients with 70 evaluable episodes of fever. Patients receiving antibiotics were excluded. Bactrim was permitted, when given as prophylaxis of Pneumocystis carinii pneumonia. If abnormalities were found on MRI, sinus aspiration was performed and the aspirate investigated. MRI abnormalities were found in 54.3% of the patients with a significantly higher occurrence of pathological changes in AIDS patients compared with HIV-infected without AIDS. In approximately 2/3 of the aspirates a probable, etiologic agent was found. However, 1/3 of these agents were atypical such as cytomegalovirus and mycobacteriae; in one patient Non-Hodgkin's lymphoma was found. The high occurrence of sinusitis in HIV-infected patients and the atypical findings in the sinus aspirates stress the importance of searching for sinusitis and the etiology to ensure the correct treatment.

Acquired Immunodeficiency Syndrome↗

PubMed2000

[Magnetic resonance imaging of patients with perianal fistulas].

Magnetic resonance imaging (MRI) of the anal canal was retrospectively evaluated during a three year period in 67 patients with suspected perianal fistulae. In six cases the surgeon, who knew the results of the MRI, found a fistula not seen on MRI while MRI showed a fistula in one patient which could not be found at surgery. We recommend MRI in cases where an experienced surgeon has difficulties mapping the fistula tract.

Adolescent↗

PubMed2000

Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins.

MCM2-7, a complex of six subunits, is an essential component of the prereplication chromatin that is assembled at Saccharomyces cerevisiae replication origins during G(1) phase. It is also believed to be the processive helicase at growing forks. To elucidate the action of MCM2-7 during the transition from initiation to elongation replication, we have focused our studies on Mcm10, a replication initiation protein that physically interacts with members of the MCM2-7 complex. We show that Mcm10 is a chromatin-associated protein that mediates the association of the MCM2-7 complex with replication origins. Furthermore, diminished interaction between Mcm10 and Mcm7, a subunit of the MCM2-7 complex, by a mutation in either Mcm10 or Mcm7 inhibits replication initiation. Surprisingly, a double mutant containing both the mcm10-1 and mcm7-1 (cdc47-1) alleles restores interaction between Mcm10 and Mcm7 and corrects all of the defects exhibited by each of the single mutants, including the stalling of replication forks at replication origins typically seen in mcm10-1 cells. This mutual compensation of defects between two independently isolated mutations is allele specific. These results suggest that Mcm10, like Mcm7, is a critical component of the prereplication chromatin and that interaction between Mcm10 and Mcm7 is required for proper replication initiation and prompt release of origin-bound factors.

Alleles↗

PubMed2000

Bilirubin- and light induced cell death in a murine lymphoma cell line.

Cells from the mouse lymphoma cell line L5178Y-R were exposed to blue light from phototherapy lamps in the presence of solutions of 160 microM bilirubin supplemented with serum albumin. HPLC analysis showed that the bilirubin solution was photooxidised as a function of increasing light dose. The cells were stained with trypan blue to score necrosis, and apoptosis was assayed by the terminal deoxynucleotide transferase assay (TdT) or by studying the nuclear structure in cells stained with propidium iodide. A rapidly developing apoptosis was observed after light doses killing 60-80% of the cells as judged from the trypan blue exclusion test. The fraction of apoptotic cells was smaller than the fraction of necrotic cells. Exposure of the cells to fractions of light at a high dose rate was compared to the effect of the same total dose at a lower dose rate given as a single fraction. No large differences were found, however, there was a tendency of a higher degree of necrosis as well as apoptosis in the cells receiving the light in fractions at a high dose rate.

Animals↗

PubMed2000

Molecular characterization of HERV-H variants associated with multiple sclerosis.

Our objective was to characterize retroviral sequences by RT-PCR with gag and env primers on RNA from RT-positive retroviral particles produced by multiple sclerosis (MS) derived B-lymphoblastoid cell lines. Sequence variants with high homology to the potentially functional subgroup RGH of the human endogenous retrovirus RTVL-H/HERV-H family were found. The same sequences were also specifically found in the particulate fraction of a series of MS patient plasma samples and were absent in controls. South-Western blots demonstrate the presence of a nucleic acid binding protein, corresponding in size and function to the nucleocapsid protein, Gag NC, of other retroviruses. We also present indications for transmission of the retrovirus to PHA-stimulated lymphocytes from healthy individuals.

B-Lymphocytes↗

PubMed2000

beta relaxation of nonpolymeric liquids close to the glass transition

Dielectric beta relaxation in a pyridine-toluene solution is studied close to the glass transition. Loss peak frequency and maximum loss both exhibit thermal hysteresis. An annealing-state-independent parameter involving loss and loss peak frequency is identified. This parameter has a simple Arrhenius temperature dependence. The same behavior is found for four other viscous liquids, indicating that the phenomenon is possibly general.

Journal Article↗

PubMed2000

The prevalence and significance of incidental paranasal sinus abnormalities on MRI.

Morphological changes in the paranasal sinuses are regularly noted on MRI, but little is known about the incidence and significance of these changes in the general population. The purpose of this study was 1) to classify the morphological changes in the paranasal sinuses seen on MRI 2) to investigate the prevalence, site and type of paranasal abnormalities and 3) to evaluate the significance of the findings by relating them to the presence of sinusitis symptoms, allergy, smoking habits and seasonal variations. In a one-year period, 404 patients referred to MRI for suspected intracranial neurological pathology were prospectively investigated. Before undergoing the scan the patients completed a questionnaire. The observed morphological conditions were classified so that mucous thickening < 5 mm was recorded as normal; > or = 5 mm, total sinus opacification or fluid and polyps as pathological. According to this classification 31.7% of the patients had pathological findings in the sinuses. A significantly higher incidence was found in the winter period and in patients with symptoms associated to sinusitis. "Blocked nose" was the only symptom occurring significantly more often in patients with pathological changes. There was no significant relationship between paranasal sinus abnormalities and sex, age, allergy, smoking habits, previous events of sinusitis or frequent events of colds. Criteria for pathological MRI findings in the paranasal sinuses are desirable and might improve the basis for a decision on the correct medical or surgical treatment.

Adult↗

PubMed1999

Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo.

The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10 and 20 pmol OS2 caused no neurological abnormalities or tissue damage. OS2 (50 pmol) caused apathy and circling towards the injection side. Histology revealed an infarct at the injection site. Injection of 50 pmol OS1 showed very little or no signs of neurotoxicity. Injection of 2.5 micromol Glu caused no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards the side of injection in the following days. Thus, OS2 greatly potentiates glutamate excitoxicity in vivo.

Animals↗

PubMed1999

Thermodynamics of reversible and irreversible unfolding and domain interactions of glucoamylase from Aspergillus niger studied by differential scanning and isothermal titration calorimetry.

The stability of three forms of glucoamylase from Aspergillus niger has been investigated by differential scanning and isothermal titration calorimetry: Glucoamylase 1 (GA1), which consists of a catalytic domain and a starch-binding domain (SBD) connected by a heavily O-glycosylated linker region; glucoamylase 2 (GA2), which lacks SBD; and a proteolytically cleaved glucoamylase (GACD), which contains the catalytic domain and part of the linker region. The structures of the catalytic domain with part of the linker region and of SBD are known from crystallography and NMR, respectively, but the precise spatial arrangement of the two domains in GA1 is unknown. To investigate the stability of the three glucoamylase forms, we unfolded the enzymes thermally by differential scanning calorimetry (DSC). Aggregation occurs upon heating GA1 and GA2 at pH values between 2.5 and 5.0, whereas no aggregation is observed at higher pH (5.5-7.5). At all pH values, the catalytic domain of GA1 and GA2 unfolds irreversibly, while SBD unfolds reversibly in the pH range 5. 5-7.5 where aggregation does not occur. The unfolding of the catalytic domain of all glucoamylase forms seems to follow an irreversible one-step mechanism with no observable reversible intermediates on the experimental time scale. SBD of GA1 unfolds reversibly, and the ratio between the van't Hoff and calorimetric enthalpies is 1.4 +/- 0.1. Assignment of peaks of the DSC profile to the domains at pH 7.5 is achieved by using two different ligands: Acarbose, a very strong inhibitor that binds exclusively to the catalytic domain, and beta-cyclodextrin, a small starch analogue of which 2 molecules bind solely to the two binding sites present in SBD. Differences are seen in the unfolding processes of GA1 and GA2 since the former unfolds with one peak at all pH values, while the calorimetric trace of the latter can be resolved into more peaks depending on pH and the chemical composition of the buffers. In general, peaks corresponding to unfolding of GA2 are more complex than the peaks of GA1 and GACD. Some part of GA2 unfolds before the rest of the molecule which may correspond to the linker region or a particular early unfolding part of the catalytic domain. This leads to the conclusion that the structure of the GA2 molecule has a larger cooperative unfolding unit and is less stable than the structures of GA1 and GACD and that the C-terminal part of the linker region has a destabilizing effect on the catalytic domain.

Acarbose↗

PubMed1999

Dry powder inhalation as a potential delivery method for vaccines.

Measles vaccine is administered to millions of children annually via a percutaneous injection. There are, however, compelling reasons to search for alternative routes of administration, especially in mass vaccination campaigns. Two key factors are (1) decreased stability of the vaccine upon reconstitution and, (2) the potential risks of contamination associated with needles. Dura has developed a unique inhaler that can deliver a powder dose via the pulmonary route for local or systemic action. The breath-actuated Spiros inhaler uses electromechanical energy to aerosolize and deliver a consistent dose over a wide range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for subsequent systemic absorption, dry-powder vaccine is size reduced to a mass median diameter between 1 and 5 microns. Small vaccine particles are blended with an inert carrier to improve dispersion. Measles vaccine formulated as a powder blend may be more thermostable than existing reconstituted formulations. The Spiros technology is available in three powder storage platforms. Two of these formats are designed specifically for moisture and/or light sensitive compounds and may be particularly suitable for delivery of measles vaccines in mass campaigns because their design (1) eliminates the need for powder reconstitution, and (2) reduces the risk of contamination.

Administration, Inhalation↗

PubMed1999

Reverse transcriptase activity and particle production in B lymphoblastoid cell lines established from lymphocytes of patients with multiple sclerosis.

We have established spontaneously formed B lymphoblastoid cell lines from long-term cultured peripheral blood mononuclear cells (PBMNCs) from multiple sclerosis (MS) patients. The MS cell lines actively produce retrovirus-like particles as well as Epstein-Barr virus (EBV). Using three different variations of the highly sensitive polymerase chain reaction (PCR)-based assays for the detection of reverse transcriptase (RT) activity, we have verified the retroviral origin of the retrovirus-like particles that are produced in very low amounts by the MS cell lines.

B-Lymphocytes↗

PubMed1999

A new transcriptional activator for amylase genes in Aspergillus.

We have cloned a regulatory gene for amylase synthesis in Aspergillus oryzae. This gene, amyR, encodes a 604-amino acid transcriptional activator with a Cys6 zinc cluster, that shows extensive homology to the DNA binding domain of GAL4 from Saccharomyces cerevisiae. The DNA binding domain of amyR binds to two types of sequences found in a number of promoters from Aspergillus genes coding for starch-degrading enzymes. One type of binding site is characterized by two CGG triplets separated by eight nucleotides. The other type has only one CGG triplet, which is followed by the sequence AAATTTAA.

Amino Acid Sequence↗

PubMed1999

Structure-function relationships in glucoamylases encoded by variant Saccharomycopsis fibuligera genes.

The mutation Gly467-->Ser in Glu glucoamylase was designed to investigate differences between two highly homologous wild-type Saccharomycopsis fibuligera Gla and Glu glucoamylases. Gly467, localized in the conserved active site region, S5, is replaced by Ser in the Gla glucoamylase. These amino acid residues are the only two known to occupy this position in the elucidated glucoamylase sequences. The data from the kinetic analysis revealed that replacement of Gly467 with Ser in Glu glucoamylase decreased the kcat towards all substrates tested to values comparable with those of the Gla enzyme. Moreover, the mutant glucoamylase appeared to be less stable compared to the wild-type Glu glucoamylase with respect to thermal unfolding. Microcalorimetric titration studies of the interaction with the inhibitor acarbose indicated differences in the binding between Gla and Glu enzymes. The Gla glucoamylase, although less active, binds acarbose stronger (Ka congruent with 10(13).M(-1)) than the Glu enzyme (Ka congruent with 10(12).M(-1)). In all enzymes studied, the binding of acarbose was clearly driven by enthalpy, with a slightly favorable entropic contribution. The binding of another glucoamylase inhibitor, 1-deoxynojirimycin, was about 8-9 orders of magnitude weaker (Ka congruent with 10(4).M(-1)) than that of acarbose. From comparison of kinetic parameters for the nonglycosylated and glycosylated enzymes it can be deduced that the glycosylation does not play a critical role in enzymatic activity. However, results from differential scanning calorimetry demonstrate an important role of the carbohydrate moiety in the thermal stability of glucoamylase.

Acarbose↗

PubMed1999

Van der Knaap's vacuolating leukoencephalopathy: two additional cases.

We present two new cases with infantile-onset megalencephaly and a characteristic magnetic resonance imaging (MRI) pattern including severe white-matter abnormalities and subcortical cysts. In one of the patients MRI at the early age of 9 months showed pronounced white matter swelling. In another patient the swelling of white matter was less pronounced at 12 years of age.

Brain Edema↗