Biomedical subjects
M Jensen
Publications and source records attributed to M Jensen.
Properties of a genetically engineered G domain of elongation factor Tu.
The G domain of elongation factor Tu (EF-Tu), representing the N-terminal half of the factor according to its three-dimensional model traced at high resolution, has been isolated by genetic manipulation of tufA and purified to homogeneity. The G domain, whose primary structure shares homology with the eukaryotic protein p21, is capable of supporting the basic activities of the intact molecule (guanine nucleotide binding in 1:1 molar ratio and GTPase activity). However, it is no longer exposed to the allosteric mechanisms regulating EF-Tu. The G-domain complexes with GTP and GDP display similar K'd values in the microM range, in contrast to EF-Tu that binds GDP much more tightly than GTP. Its GTPase shows the characteristics of a slow turnover reaction (0.1 mmol X sec-1 X mol-1 of G domain), whose rate closely corresponds to the initial hydrolysis rate of EF-Tu X GTP in the absence of effectors and lies in the typical range of GTPase of the p21 protein. Of the EF-Tu ligands only the ribosome displays a clear effect enhancing the G-domain GTPase. Our results suggest that the middle and C-terminal domain play an essential role in regulating the activity of the N-terminal domain of the intact molecule as well as in the interactions of EF-Tu with aminoacylated tRNA, elongation factor Ts, and kirromycin. With the isolation of the G domain of EF-Tu, a model protein has been constructed for studying and comparing common characteristics of the guanine nucleotide-binding proteins.
[Endometriosis causing intestinal stenosis].
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In vitro studies on the effect of yolk sac antisera on functions of the visceral yolk sac: I. Pinocytosis and transport of small molecules.
The production of congenital malformations by the administration of teratogenic antisera to pregnant animals has been reported from many laboratories. This work has focused our attention on the importance of the yolk sac placenta in supporting the rat embryo during early organogenesis and the significance of yolk sac dysfunction in rodent teratogenesis. The studies reported in this article deal with the effect of teratogenic antisera on the process of yolk sac transport; specifically pinocytosis (as measured by 14C-sucrose uptake) and small-molecule transport utilizing 14C-alpha-aminoisobutyric acid (AIB) and 3H-2-deoxyglucose (DOG). We sought to determine whether several different yolk sac localizing antibodies interfere with these transport processes, and, if so, which transport processes were most affected. The results of the experiments indicated that teratogenic antisera interfered with the process of pinocytosis in the yolk sac and that pinocytosis can be reduced as much as 40%. Nonteratogenic antisera, even when they localized in the yolk sac, did not interfere with the process of pinocytosis. Furthermore, the teratogenic antisera did not interfere with the transport of small molecules (either AIB or DOG) in the yolk sac. These results indicated that while fluorescent localization of an antiserum in the yolk sac did not invariably indicate the potential for teratogenicity, it is likely that the reduction in pinocytosis may directly correlate with the teratologic and embryopathic events. This work reaffirms the view that the yolk sac in important during rodent organogenesis and that yolk sac dysfunction can play an important role in the development of congenital malformations.(ABSTRACT TRUNCATED AT 250 WORDS)
Methylphenidate challenge in a manic boy.
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Acquired diverticulosis of the small intestine: case reports and literature review.
Eleven cases of small bowel diverticulosis are discussed. Four patients presented with perforation, five with other symptoms attributable to this condition and in two patients diverticulosis was considered an incidental finding. A review of the literature suggests that small bowel diverticulosis may be: present in up to 1.3% of the population; associated with symptoms in approximately 50% of patients, and associated with acute surgical complications in 10% of patients. This may be a disorder of intestinal motility associated with colonic diverticulosis and related to other disorders of smooth muscle and myenteric plexus. Small bowel diverticulosis should not be regarded as a rare, incidental and inconsequential finding.
Polarized neutron capture on 13C.
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[Fractionated homogeneous whole body irradiation prior to bone marrow transplantation].
At the University of Kiel, myeloid and acute lymphatic leukemia is treated since 1983 by total-body irradiation applied prior to bone marrow transplantation. Dose deviations in the midplane caused by the irregular surface and tissue inhomogeneities of the patient are reduced down to +/- 3.5% compared to the central ray, with the help of CT-based individual compensators. This method prevents above all an excessive dose to the lungs. The radiobiologic advantages of fractionated irradiation have been employed for all patients treated hitherto (n = 9). At present, a total body dose of 12 Gy in six fractions is applied within three days. There were no undesired acute radiogenic reactions except a mild acute mucositis found in all patients. Chronic side effects, especially in the lungs, were not demonstrated, too. However, the average follow-up time of 149 days has been rather short. One patient died from relapse of leukemia after a total dose of 10 Gy, another patient died because the transplanted bone marrow was rejected, and a third died from catheter sepsis. Six out of nine patients are in complete remission with a maximum index of Karnofsky. The limited experiences gained hitherto show that the homogenous accelerated-fractionated total-body irradiation offers essential advantages compared to non-compensated single dose irradiation with respect to the prevention of undesired radiogenic effects in sound tissues and that its therapeutic efficacy is at least the same.
Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)--a possible new treatment of methanol poisoning.
High doses of 4-methylpyrazole (4-MP) could be administered to monkeys in long- and short-term experiments without yielding any general toxicity or any toxic influence on the retinal photoreceptors, the conduction of impulses through the retina or on the activity in the inner nuclear layer detectable by recording the electroretinogram (ERG). Both series included a low dose (20 mg/kg) and a high dose level (100 mg/kg), the former being a tentative therapeutic dose. In the first series the substance was administered for 6 weeks and the toxicity regarding clinical signs, hematology and blood chemistry, and gross and microscopic pathology evaluated. Furthermore ophthalmoscopy with assessment of the fundus structures and recordings of the ERG were performed. The second series was mainly concerned with revealing of any direct effect of 4-MP on the ERG. Because of the low toxicity of 4-MP and its powerful inhibitory capacity on alcohol dehydrogenase, the substance should prove a potential tool in clinical alcohol research and an effective antidote in clinical situations where inhibition of alcohol dehydrogenase (ADH) is the key to a successful outcome of, for example, methanol and ethylene glycol poisoning.
Hereditary persistence of fetal haemoglobin (HPFH) in conjunction with a chromosomal translocation involving the haemoglobin beta locus.
An HPFH syndrome was found in a woman and her daughter who also carry a 'balanced' cyclic translocation of chromosome segments involving four chromosomes, with one break point located in the region of the Hb beta locus. This HPFH is characterized by 5% and 8% Hb F in peripheral blood, uneven distribution of Hb F in the red cells, and a G gamma/G gamma + A gamma ratio of 0.4. The mapping of the non alpha gene cluster shows no detectable deletion in the entire gamma-delta-beta-globin gene region.
The burn situation in Gizan. Planning and implementation of a Burns Unit at the King Fahd Central Hospital, Gizan, the Kingdom of Saudi-Arabia.
A 500-bed referral hospital was designed in 1975 in the health region of Gizan , the Kingdom of Saudi-Arabia. According to an agreement of 1981 between the Danish Ministry of the Interior and the Ministry of Health for the Kingdom of Saudi-Arabia, Danish cooperation to start and run this hospital was initiated. At the end of 1982 an investigation was made as to whether there was a need for a Burns Ward, a Burns Unit or a Burns Center. The epidemiology (number, severity and causes of burns) in the Gizan region (500 000 inhabitants) was investigated and all in-patients were examined, after which a recommendation to establish a Burns Unit was made. The Danish personnel arrived in April 1983, and the first patient was admitted to the Unit in May 1983. During the first 5-month period 46 patients with burns and 77 other patients requiring plastic surgery were treated. It seems therefore that the need for a Unit for Burns and Plastic Surgery has been proved. The number of inhabitants in the Gizan health region corresponds to that of the municipality of Copenhagen (500 000), and in the future the epidemiology, treatment and results of treatment will be compared in these two areas.
[Optimization of dose distribution in whole body irradiation by means of compensators].
In case of whole-body irradiation prior to bone marrow graft, an undesired irregular dose deposition in the median body plane is caused by the irregular body shape and the tissue inhomogeneities of the patient, which can amount up to 50% of the planned focal dose in case of laterally opposing irradiation. A procedure is proposed allowing to modify the dose distribution in the irradiated body systematically by means of compensators. Such compensators are produced with the aid of an adequate number of serial CT scans, a programme system considering these data and the individual irradiation geometry, and a computer-controlled cutter working in three dimensions. First a casting mould is manufactured which is then filled up with an adequate compensation material. The actual compensation data and the planned irradiation geometry are controlled before and during the treatment. Taking into consideration the individual shapes and the different tissue densities, it is not only possible to prevent the dose inhomogeneities mentioned above but also to introduce by means of a special programme part regions with a higher or lower dose deposition at any point of the irradiation field, at the therapeutist 's discretion.
[Prenatal diagnosis of hemoglobin anomalies].
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Human arterial wall cells secrete factors that are chemotactic for monocytes.
Macrophages and arterial smooth muscle cells comprise the cellular components of the atherosclerotic plaque. The vessel wall accumulation of macrophages occurs by a process of increased circulating monocyte migration into the vessel wall. In these studies it is demonstrated that human macrophages and arterial smooth muscle cells in culture secrete potent chemotactic factors for freshly isolated human monocytes. In contrast, human fibroblast-conditioned medium has no chemotactic activity. The effect of macrophage-conditioned medium is a function of macrophage differentiation and can be potentiated by macrophage activation. These results suggest that secretory products of human macrophages and arterial smooth muscle cells may be important stimuli for increased monocyte migration into the vessel wall in vivo.
The primary structure of the glycan moiety of pseudomurein from Methanobacterium thermoautotrophicum.
After treatment of isolated cells walls of Methanobacterium thermoautotrophicum with sodium hydroxide or anhydrous hydrazine, water soluble glycan strands were obtained. These consisted of alternating (beta 1-3)-linked D-glucosamine and (alpha 1-3)-linked L-talosaminuronic acid residues and their length was about 25 disaccharides. Some of the L-talosaminuronic acid residues remained linked to either glutamic acid or the peptides N-gamma-glutamylalanine and N epsilon-(gamma-glutamylalanyl)lysine, indicating that the peptide moiety of pseudomurein is bound to the carboxyl group of talosaminuronic acid via the amino group of glutamic acid.
The developmental change in the G gamma and A gamma globin. Proportions in hemoglobin F.
The proportions of G gamma and A gamma globins in hemoglobin F were determined in fetuses around the 20th week of gestation, newborns, and children 3 weeks to 5 months of age. In the last group, the G gamma/G gamma + A gamma ratio decreased continously; there was a good correlation between the decline of G gamma with respect to total gamma and the decline of Hb F (r = 0.88). In contrast, there was virtually no difference in the gamma globin composition of Hb F between the fetuses and the newborns, i.e. in late pregnancy, the decrease in the synthesis of both gamma globins appears to be proportionate. The G gamma and A gamma globin genes may be inactivated in a sigmoidal fashion with time, thus producing a G gamma/G gamma + A gamma ratio which at first changes only slightly and then declines linearily.
Low density lipoprotein receptor activity in freshly isolated human blood monocytes and lymphocytes.
Circulating human monocytes and lymphocytes were isolated by counterflow and density gradient centrifugation. Binding and degradation of low density lipoprotein (LDL) occurred predominantly in monocytes and to a much lesser extent in lymphocytes. The findings were consistent with greater LDL receptor activity in freshly isolated monocytes than lymphocytes, in keeping with differences in other cell surface receptors between these two cell types. Therefore, when freshly isolated mixed mononuclear cells are used to study LDL receptor activity in vivo in humans, careful attention needs to be given to the proportions of monocytes and lymphocytes, or alternatively, relatively pure preparations of monocytes should be used.