Search PubMed⌕ Search

Biomedical subjects

T Christensen

Publications and source records attributed to T Christensen.

At least 91 records · Page 5Linked to original sources
PubMed1996

The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload.

Long-term follow-up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging. Reduction in the Hb requirement ( > or = 50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration. It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.

Adolescent↗
PubMed1996

Recurrent ophthalmoplegia in childhood: diagnostic and etiologic considerations.

We present two patients with recurrent painful ophthalmoplegia starting in early childhood. Clinically, both patients fulfilled the criteria for ophthalmoplegic migraine. In one case, magnetic resonance investigations were performed following the second attack, between the third and fourth and during the fourth attack. The left third cranial nerve was significantly thickened in its course from the brainstem through the prepontine cistern to the cavernous sinus during the attacks and moderately thickened between the attacks. In the second case, magnetic resonance imaging was performed during the 14th attack, when the oculomotor nerve dysfunction was almost permanent, and the imaging demonstrated a swollen oculomotor nerve. Whether these findings are pathognomonic of ophthalmoplegic migraine awaits further reports using magnetic resonance imaging in infants showing recurrent painful ophthalmoplegia of early onset.

Child↗
PubMed1996

The central nervous system in Tay syndrome.

Trichothiodystrophy (brittle sulfur-deficient hair) is a marker for several autosomal recessive neurocutaneous syndromes with neurological manifestations and mental retardation. In Tay syndrome, the trichothiodystrophy is accompanied by congenital ichthyosis, short stature, delayed physical and mental development and pyramidal tract signs with increase in muscular tone and brisk tendon reflexes. The pathogenesis of these neurological manifestations is not fully elucidated. We present a case of Tay syndrome in which a cranial MRI revealed an almost total lack of myelin within the cerebral hemispheres and a patchy hypomyelination of the cerebellum. In accordance, a strongly prolonged visual evoked response pointed to a dysfunction of the white matter in Tay syndrome.

Ataxia↗
PubMed1996

Serum procollagen III peptide concentration in iron overload.

Patients with severe iron overload may develop hepatic fibrosis due to iron toxicity. Unfortunately, the follow-up of the fibrogenic activity during treatment by histological examination of tissue biopsies carries potential side effects, and may therefore not be justified ethically. Recently, the serum concentration of procollagen type III peptide (S-PIIINP) has been shown to be a valid serum marker of the activity of collagen metabolism in conditions with hepatic fibrosis unrelated to iron overload. In order to evaluate the potential usefulness of this test in patients with fibrosis due to iron overload, we investigated the relationship between the PIIINP serum concentration and the size of iron overload in 18 patients with hereditary haemochromatosis (HH) and in 14 patients with transfusional iron overload. A close correlation was found between S-ferritin and S-PIIINP (r = 0.73, p < 0.0001). Follow-up of 6 patients during iron depletion treatment revealed a normalization of the serum aminotransferase concentration before normalization of S-PIIINP was found. This may indicate that excess iron directly induces an increase in fibrogenesis rather than the increased fibrogenesis is secondary to hepatocellular injury caused by iron excess. Thus, serial measurements S-PIIINP may be useful in follow-up of the fibrogenic process due to iron overload.

Biomarkers↗
PubMed1996

Fifty-Hertz magnetic field exposures of premature infants in a neonatal intensive care unit.

In this study the magnetic flux density in and around incubators of a neonatal intensive care unit was registered and mapped. The mean 50-Hz magnetic flux densities in an incubator were typically in the range of 0.2-1 microT, with maximum values around 1.5 microT. For 1 incubator, harmonics contributed to the field substantially. The field levels varied depending on the type of equipment, the positioning of the electronics and the position of the 240-volt main plugs. The positioning of the infant in the incubator and the precise mattress position in the incubator affected the magnetic flux density to a great extent, as did the positioning of the electronic monitoring and treatment equipment. The flux density values found were fairly low as compared to magnetic field levels present at some work places where high electric currents are used. In intensive care units, however, the duration of exposure can be very long, especially for premature infants. The fields can also be compared with the magnetic field levels of residences and are then approximately 100 times higher. Further studies are necessary -it seems important to record magnetic fields and attempt to reduce the levels. Such a reduction can be achieved by reducing the field from the incubators but also by changing the electronic equipment around the incubators or increasing the distance to the incubator. Further research should of course also study any mechanism by which magnetic fields can affect cells and organisms. Compared to the risks many of these infants are exposed to, it is difficult to say whether the magnetic field levels measured can represent a significant additional risk factor. However, this is an area where one should adopt a prudent avoidance strategy, particulary considering how easily these fields can be reduced, mainly through redesign of the various equipment.

Environmental Exposure↗
PubMed1995

[Molybdenum cofactor deficiency. Clinical symptoms and diagnostic strategy].

The clinical, neuroradiological and biochemical findings in two siblings with molybdenum cofactor deficiency are presented. A search for this deficiency is advocated in each case of unexplained refractory neonatal convulsions. Early diagnosis is prompted by the often rapid fatal outcome and the availability of methods for prenatal diagnosis. Diagnosis may be missed or delayed on standard metabolic screening for several reasons discussed. Magnetic resonance imaging in this condition seems to be rather characteristic.

Brain↗
PubMed1995

Mutational analysis of the roles in catalysis and substrate recognition of arginines 54 and 305, aspartic acid 309, and tryptophan 317 located at subsites 1 and 2 in glucoamylase from Aspergillus niger.

The mutants Arg54-->Leu, Arg54-->Lys, Arg305-->Lys, Asp309-->Glu, and Trp317-->Phe, located at subsites 1 and 2 in glucoamylase from Aspergillus niger, provide insight into the importance of specific hydrogen bonds and hydrophobic interactions in substrate recognition, catalytic mechanism, and stability. As suggested from the crystal structure of a closely related glucoamylase [Aleshin, A. E., Firsov, L. M., & Honzatko, R. B. (1994) J. Biol. Chem. 269, 15631-15639], Arg54 in subsite 1 hydrogen bonds to the key polar group 4'-OH of maltose. The two mutants of Arg54 display losses in transition-state stabilization of 16-21 kJ mol-1 in the hydrolysis of different maltooligodextrins, which originate from a [(1.2-1.8) x 10(3)]-fold reduction in kcat and changes in Km ranging from 25% to 300% of the wild-type values. Arg305 similarly hydrogen bonds to 2'-OH and 3-OH, located at subsites 1 and 2, respectively. Arg305-->Lys glucoamylase is not saturated at concentrations of maltose or maltoheptaose of 400- and 40-fold, respectively, the Km of the wild-type enzyme. This mutant also has highly reduced kcat. On the other hand, for the alpha-1,6-linked isomaltose, the Lys305 mutant surprisingly has the same Km as the wild-type enzyme, while kcat is 10(3)-fold reduced. Arg305 is thus an important determinant in the distinction of the alpha-1,4 to alpha-1,6 substrate specificity. Arg305 interacts electrostatically and hydrophobically with the side chains of Asp309 and Trp317.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1995

Renal growth during pregnancy in insulin-dependent diabetic women. A prospective study of renal volume and clinical variables.

Kidney volume was measured during pregnancy in insulin-dependent diabetic women by an ultrasound technique and prognostic value of these measurements evaluated. A prospective study was performed on 87 pregnant women with insulin-dependent diabetes attending the maternity clinic of Aarhus Kommunehospital. Patients with proliferative retinopathy alone, hydronephrosis, or nephrotic syndrome were excluded. The patients were grouped according to onset and duration of diabetes and to vascular lesions; group I (n = 35, White class B+C), group II (n = 11, White class D0), group III (n = 26, White class D+), and group IV (n = 15, White class F+F/R). The patients visited the hospital every 2 weeks during pregnancy for general obstetric and glycaemic control and blood sampling. The volume of both kidneys was measured by a computerized nephrosonograph during the three terms of pregnancy, the puerperium and 4 months postpartum. The kidney volume increased significantly in all four groups from first to third trimester. In the third trimester the kidney volumes were 375 +/- 68 ml (I), 341 +/- 50 ml (II), 362 +/- 63 ml (III), and 343 +/- 54 ml (IV). The kidney volume in the third trimester was positively correlated with creatinine clearance (r = 0.33, P < 0.01) and inversely correlated with creatinine in serum (r = -0.27, P = < 0.02). Total kidney volume decrease (in percent) defined as the difference of maximal volume and value at 4 months postpartum was inversely correlated to albuminuria in the third trimester (r = -0.25, P < 0.05) and vascular lesions of the patients: (mean +/- SEM) 37 +/- 4% (I), 25 +/- 7% (II), 19 +/- 5% (III), and 11 +/- 7% (IV), P < 0.01. In the puerperium, kidney volume decreased significantly from third trimester in groups I, II, and III, whereas we observed no change in group IV. Six of 15 women in groups II and III with kidney volume < 300 ml and normoalbuminuria in the first trimester developed persistent microalbuminuria after pregnancy (P < 0.02). The renal volume in insulin-dependent diabetic women increases significantly during pregnancy and is inversely related to the vascular lesions of the patients. The decrease in renal volume after pregnancy is related to the albuminuria at the end of pregnancy. Women with longstanding diabetes, White class D (= groups II+III), and kidney volume < 300 ml in the first trimester have a high risk of developing permanent microalbuminuria after pregnancy.

Adult↗
PubMed1995

Microdialysis as a tool for in vivo investigation of glutamate transport capacity in rat brain.

The role of glutamate as a possible mediator of neurodegeneration is well described, and the homeostasis of extracellular glutamate is considered of major importance when addressing the pathogenesis of excitatory neurodegeneration. Applying the 'indicator diffusion' method to the microdialysis technique, we present a method that is suitable for the in vivo investigation of the capacity of cellular uptake of glutamate. Using 14C-mannitol as reference, we measured the cellular extraction and the cell membrane permeability of the test substance 3H-D-aspartate in the corpus striatum of the rat brain. The cellular extraction fraction of 3H-D-aspartate was 0.29, and the cell membrane permeability 2.24 x 10(-4) cm/s. In the presence of the glutamate-uptake blocker DL-threo-beta-hydroxyaspartate (THA) the extraction of 3H-D-aspartate was completely abolished, indicating that extraction of 3H-D-aspartate was due to cellular uptake by glutamate transporters. The cell membrane permeability towards 3H-D-aspartate was reduced by approximately 98% due to THA, indicating that the cell membranes per se are highly resistant to diffusion of 3H-D-aspartate. It is concluded that the present method can be used in studying the capacity of the glutamate transporters in vivo.

ATP-Binding Cassette Transporters↗
PubMed1995

Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients.

The ability to quantitate transfusional iron overload is crucial for determining the need for and the efficacy of chelation therapy in patients with long-standing transfusion-dependent anaemias. We evaluated the usefulness of some indirect measures of iron overload in estimating the iron concentration in the liver--the most important iron storage organ--in 26 non-chelated adult non-thalassaemic patients. Liver iron concentration was determined non-invasively by magnetic resonance imaging (MRI). The standard error of the estimated liver iron concentration was 80 mumol Fe/g dried liver tissue when using the number of transfused blood units, and 93 mumol Fe/g when using a serum ferritin assay. Follow-up in 11 patients (12-48 months) revealed that serum ferritin is a poor measure of the liver iron concentration during iron chelation. However, this discrepancy was individually different and seemed to be dependent on the erythropoietic marrow activity. By monitoring the liver iron concentration by MRI, we compared the efficacy of chelation with desferrioxamine given either by subcutaneous continuous infusions or by bolus injections. Depletion of liver iron stores could be achieved efficiently by both regimens.

Adolescent↗
PubMed1995

In vivo diagnosis of Hallervorden-Spatz disease.

The authors present the MRI findings of two children with insidious walking difficulties, signs of corticospinal tract involvement, and signs and symptoms of extrapyramidal dysfunction such as rigidity and generalized dystonia, the latter with predominance of oromandibular involvement. In one child, MRI revealed prominent hypo-intensity in the globus pallidus and in the substantia nigra on T2-weighted spin echo images, consistent with iron deposition and thus with previous post-mortem findings of Hallervorden-Spatz disease. In the other case, the hypo-intensity was restricted to the globus pallidus, in which a small area of hyperintensity in its internal segment was demonstrated--the so called 'eye-of-the-tiger' sign. The authors propose that a combination of previously mentioned neurological signs with these specific MRI findings is highly suggestive of an in vivo diagnosis of the late infantile type of HSD.

Fatal Outcome↗
PubMed1995

B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus.

On several occasions we have observed retrovirus-like particles (RVLPs) by transmission electron microscopy (EM) of cultured T cells from a patient with MS. Later we established spontaneously formed B-lymphoblastoid cell lines (LCLs) from a patient with an MS-like disease and from another patient with MS who had a reactivated Epstein-Barr virus (EBV) infection. Both LCLs were found by EM to produce RVLP and EBV particles. Reverse transcriptase (RT) assays were positive in purified viral material from both LCLs. To substantiate these findings we initiated an intensified culturing procedure and were able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls. All LCLs were found to produce both RVLP and EBV particles by EM. Whether the putative new retrovirus(es) and EBV have any causal relationship to MS is still not known, but the findings support this possibility.

Adult↗
PubMed1994

NMR spectroscopy of exchangeable protons of glucoamylase and of complexes with inhibitors in the 9-15-ppm range.

1H-NMR spectra have been recorded for glucoamylases I and II from Aspergillus awamori var. X100 and from A. niger in the 9-15-ppm region. At least 17 distinct peaks, many of them arising from single protons, are observed. These are designated A-Q, A being the furthest downfield. At least 9 of these are lost rapidly by exchange when the enzyme is placed in D2O. Peaks A, B, E and H undergo distinct shifts with pH change in the pH region 3-7. Several others undergo smaller shifts. Small differences are also seen between the enzymes from the two different sources. Binding of the pseudotetrasaccharide inhibitor acarbose leads to a 0.50-ppm downfield shift of peak B, other smaller changes, and retention of two additional protons in D2O. delta-D-gluconolactone induces shifts in peaks E, H, and L. The slow substrate maltitol causes peak A to broaden and shift, peaks J and K to shift and a new or greatly shifted resonance to appear at 15.4 ppm. It disappears as the maltitol is hydrolyzed. Treatment with iodoacetamide or diethyl pyrocarbonate leads to disappearance of peak D at 12.3 ppm. When this peak was irradiated strong nuclear Overhauser effects (NOE) were observed at 8.01 ppm and 7.22 ppm, positions expected for the C epsilon 1 and C delta 2 protons of an uncharged imidazole ring. We identify D as arising from the N epsilon 2 proton of His254 which is uncharged except at the lowest pH values. Other NOE and two-dimensional NOE spectra have provided additional information. Three mutant forms of the A. niger enzyme, in which tryptophan residues have been replaced by phenylalanine, have been examined. Because of shifts induced by changes in ring current and other environmental effects it is hard to make a direct identification of the resonances from the replaced indole NH protons. However, on the basis of a distinct NOE between peaks E and H we have identified these resonances as arising from the indole NH protons of Trp52 and Trp120. Other possible assignments are considered. The NMR spectra of the glucoamylases I, which have a starch binding domain of about 104 residues at the carboxyl terminus, show four sharp resonances in the 9.7-10.6-ppm range that are not present in the glucoamylases II, which lack this domain. These resonances no doubt represent the four indole NH ring protons from Trp543, Trp562, Trp590 and Trp615. Three of these are very sharp suggesting a high mobility of this domain.

Aspergillus↗
PubMed1994

A putative new retrovirus associated with multiple sclerosis and the possible involvement of Epstein-Barr virus in this disease.

Since tropical spastic paraparesis in 1985 was found to be associated with HTLV-I infection, it has been suggested that a retrovirus might be involved in multiple sclerosis (MS). Our group has studied long-term cultures of cerebrospinal fluid cells and peripheral blood mononuclear cells from MS patients and controls with the purpose of elucidating the possible involvement of a retrovirus in MS. For an extended period electron microscopical analysis (EM) of T-cell lines, derived from MS patients and controls and cultured for 4 weeks was performed. In two cultures obtained 8 months apart from a patient with progressive MS, retrovirus-like particles were observed in 1-2% of the cells examined. Recently a B-lymphoblastoid cell line (LCL) producing retrovirus-like particles and EBV was established from a 30-year-old male patient with a chronic progressive myelopathy, clinically resembling multiple sclerosis. Similar cell lines have now been established from two MS patients. The retrovirus-like particles produced by the LCL have been purified by gradient ultracentrifugation. In the purified material reverse transcriptase assays are clearly positive in the gradients where EM shows retrovirus-like particles. Antigen characterization, nucleic acid sequence analysis and antibody studies are now being performed. The retrovirus found is definitively different from other known human retroviruses. It has previously been found that 100% of patients with MS have antibodies against EBV, in contrast to controls where only 86-95% have antibodies against this virus. Previous epidemiological studies have pointed toward a post-pubertal primary EBV infection as an important event in the induction of MS disease. These studies have now been substantiated by our group. Though it is still unknown whether EBV infection is a prerequisite for development of MS or whether the 100% EBV seropositivity is a consequence of the MS disease, we have put forward the hypothesis that the etiological agent for development of MS and MS-like diseases is a new hitherto uncharacterized retrovirus, whereas development of neurologic disease is related to or even dependent on a delayed infection with a virus from the herpes group, most likely EBV. This dual infection hypothesis has been analyzed and was found to be in accordance with the most consistent epidemiological characteristics of MS. We have previously, also from epidemiological data, negated retroviruses, behaving as the known human retroviruses, as an independent cause of MS.

Adult↗
PubMed1994

Changes in mRNA for metabotropic glutamate receptors after transient cerebral ischaemia.

Using a rat 4-vessel occlusion model of cerebral ischaemia we studied the changes in the mRNA level for the metabotropic receptor subtypes mGluR1 alpha, mGluR1 beta, mGluR2, mGluR3, mGluR4, and mGluR5 by means of in situ hybridization with oligonucleotides. After 24 hours of reperfusion the mRNA levels were significantly increased for mGluR2 and mGluR4 while it was significantly decreased for mGluR5. These results suggest that vulnerable neurones react to an increased extracellular glutamate concentration by differential regulation of the mRNA for metabotropic glutamate receptor subtypes which perhaps reflects the different pre- or postsynaptic location and different involvement in ischaemic neurodegeneration.

Animals↗
PubMed1994

Characterisation of a trisulphide derivative of biosynthetic human growth hormone produced in Escherichia coli.

A novel protein derivative has been found during process development of biosynthetic human growth hormone; it has been characterised as human growth hormone with a Cys182-Cys189 trisulphide bridge. We have not been able to find a previous report in the literature about this kind of derivative. The characterisation was obtained partly on the full-length derivative and partly on a tryptic fragment of the derivative. The full-length derivative was characterised by reduction with 1,4-dithiothreitol followed by electrospray mass spectrometry, treatment with cysteine and measurement of hydrogen sulphide liberation upon cysteine treatment. The tryptic fragment from peptide mapping was characterised by amino acid analysis, amino acid sequencing and mass spectrometry. All data indicated an extra sulphur atom in the Cys182-Cys189 cystine bridge.

Amino Acid Sequence↗