Biomedical subjects
Publications and source records attributed to S Eriksson.
We have determined the affinity of human deoxycytidine kinase with respect to new fluorescent N-methylanthraniloyl cytidine derivatives or non fluorescent enantiomeric cytidine analogues. New results regarding the enantioselectivity and the mechanism of the enzyme are presented.
Cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK) and the mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK) phosphorylate deoxynucleosides and their analogs. Recombinant human TK1 only phosphorylated beta-D Thd, but recombinant TK2, dCK and dGK all phosphorylated equally well beta-D and beta-L as well as to some extent alpha-D and alpha-L deoxynucleosides.
A series of analogues of L-adenosine and of L-guanosine, including beta-L-dA, beta-L-Ado, beta-L-araA, and beta-L-dG, have been shown to be substrates of human deoxycytidine kinase thus demonstrating the complete lack of enantioselectivity of this enzyme.
Several 1-deazapurine nucleosides were tested for their biological activity, anti-HIV-1, cytotoxicity and inhibition of adenosine deaminase (ADA). A2780 human ovarian cancer cells and the deoxycytidine kinase (dCK) deficient variant AG6000, used to determine whether dCK plays a role in their activation, showed a similar sensitivity to the analogs. This is in line with substrate specificity tests, which revealed a very low affinity of dCK.
Several N-3 substituted carboranyl Thd analogs were synthesized. These agents as well as some non-boronated nucleosides were evaluated in phosphoryl transfer assays with recombinant human TK1 and TK2. For some carboranyl thymidine analogs, TK1 phosphorylation rates approached 38% that of thymidine. Their in vitro cytotoxicty appeared to correlate with the TK1 levels in the tested cells. In some cases increased uptake in tumor cell nuclei compared with the surrounding cytoplasm was detected in vitro.
2'-Deoxy-beta-L-5-azacytidine(L-Decitabine), beta-L-5-azacytidine, and derivatives were stereospecifically prepared starting from L-ribose or L-xylose. D- and L-enantiomers of 2'-deoxy-beta-5-azacytidine were weak substrates of human recombinant deoxycytidine kinase (dCK), whereas both enantiomers of beta-5-azacytidine or the L-xylo-analogues were not substrates of the enzyme. None of the reported derivatives of beta-L-5-azacytidine was a substrate of human recombinant cytidine deaminase (CDA).
The structures of the bound 13C/2H double-labelled 2'(R/S), 5'(R/S)-2H2-1',2',3',4',5'-13C5-2'-deoxyadenosine and the corresponding 2'-deoxycytidine moieties in the complexes with human deoxycytidine kinase (dCK) have been characterized for the first time by the solution NMR spectroscopy, using Transferred Dipole-Dipole Cross-correlated Relaxation and Transferred nOe experiments. It has been shown that the ligand adopts a South-type sugar conformation when bound to dCK.
Explore the source record for details and available documents.
Even if the mechanisms and etiology of delirium still require further clarification, this article works on the assumption that delirium is caused by stress factors acting on the brain to such an extent that the brain can no longer cope. Therefore, social and environmental factors involving high levels of stress will cause delirium in the elderly. The influence of these factors is obviously very complex with several potential interacting mechanisms between different factors. Since studies on this subject are limited to certain aspects of the complex topic discussed, only narrowly focussed systematic knowledge on this topic is available. However, it can be concluded that hospital admission for example is an important risk factor for developing delirium.
Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection (250-650 ml during the first 2 days) and administration of low-molecular weight dextran was evaluated in a prospective controlled trial. Fifty-two patients were randomized to hemodilution therapy and 50 to a control group; the two groups were comparable in important prognostic variables. Mean hemoglobin was reduced from 147 to 127 g/l, hematocrit from 43 to 37% and, in a subsample of patients, whole-blood viscosity at a shear rate of 23 sec-1 from 7.0 to 4.3 cps over the first 2 days. Hemodilution was then maintained by repeated dextran infusions. Of the hemodiluted patients, 85% improved in neurological scoring over the first 10 days as compared to 64% of the control patients (p less than 0.025). The case fatality rate during the first 3 months was little affected by hemodilution. Among the survivors, 8% of the hemodiluted and 31% of the non-hemodiluted patients were unable to walk at 3 months. The proportion of surviving patients still hospitalized at the 3-month follow-up was 13% in the hemodilution group and 39% in the control group (p less than 0.01). The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infarction, and it improves the overall clinical outcome over the first 3 months.
In a prospective controlled trial we compared the clinical outcome for unselected acute stroke patients in a non-intensive stroke unit (n = 110) and in general medical wards (n = 183). The patients were comparable in age, marital state and functional impairment on admission. Case fatality rates over the first year after the stroke were similar in the two groups. By three months after the stroke, 15% of the survivors initially admitted to the stroke unit and 39% of those admitted to general medical wards remained hospitalized (p less than 0.001). The corresponding figures by one year after the cerebrovascular accident were 12% and 28%, respectively (p less than 0.05). A greater proportion of surviving stroke unit patients was independent in walking (0.10 greater than p greater than 0.05), personal hygiene (p less than 0.05) and dressing (p less than 0.001). Essential features of the stroke unit are team work headed by a stroke nurse, staff, patient and family education and very early onset of rehabilitation. We conclude that this strategy improves functional outcome and reduces the need for long-term hospital care.
The clinical outcome in 110 patients admitted to a non-intensive stroke unit was compared to that in 183 patients treated for acute stroke in general medical wards. At entry, the two groups of patients were closely similar in all prognostic indicators. Subsets of patients were analyzed in an attempt to identify groups that benefit more than others from stroke unit care. The stroke unit regime had little effect on short-term and long-term mortality rates in the entire stroke population as well as in subgroups. But after the care in the stroke unit, the need for long-term hospitalization in survivors was reduced (p = 0.0001). This difference in favour of the stroke unit was independent of the patients' age, the extent of neurological deficit on admission and previous history. In subgroups where the general prognosis is fair or good (minor neurological deficits and less than 75 yrs), SU care accelerated the process of rehabilitation, but the need for institutional care very late after the stroke was influenced only little. In groups with a poor general prognosis (major deficits and greater than or equal to 75 yrs), the ultimate proportion of patients able to return home was enhanced by SU care. It is concluded that care in a stroke unit benefits the great majority of stroke patients and that such a unit should be designed to admit all acute stroke patients without selection.
The relative importance of motor, perceptual, and some cognitive functions for self-care ability was analyzed in a representative sample of 109 subjects within 2 weeks of acute stroke. Forty-nine patients (45%) were dependent or partly dependent in self-care. Profound motor dysfunction was present in 39%, low-order perceptual deficits in 10%, high-order perceptual deficits in 60%, and disorientation in time and space in 13% of the patients. There was a significant covariation between motor function and self-care ability and between low-order perception and orientation function. Low-order and high-order perception covaried only weakly. Discriminant analyses showed that the actual level of self-care proficiency could be correctly predicted in 70% of the cases by the 4 indexes of motor function, low-order perception, high-order perception, and orientation. The dominating predictor was motor function, and the next highest was high-order perception. When a program for early training is designed with the aim to alleviate long-term self-care disability after stroke, correct assessment of motor and perceptual functions in the individual stroke patient is essential.
There is an increased risk of developing gastric carcinoma after surgery for peptic ulcer disease in humans. It is often claimed that alkaline reflux from the intestine to the stomach is a carcinogenic factor of importance in this development. In a rat model which mimics the procedures done in humans, different investigators have found an astonishingly high frequency of malignant changes. We report our findings in 19 rats operated with gastroenterostomy without resection, of which 9 developed dysplastic changes. In seven (37%) these could be classified as carcinomas or high grade dysplasia. This frequency of malignant changes is lower than that found by others. The histological classification, however, reveals substantial difficulties which are discussed. Mucin histochemistry revealed an intestinal type of cancer.
The lumbar spine of 14 cadavers was studied both by 153Gd dual photon absorptiometry (DPA) and quantitative computed tomography (QCT) at 96 and 125 kVp. The intact spine and the individual vertebrae were analyzed. After these measurements the ash content of the vertebral body, the posterior elements, and the transverse processes was determined. The fat content of the vertebral body as well as its volume was also measured. With DPA, the bone mineral content (BMC) determined in situ as well as on excised spine specimens correlated highly with the amount of total vertebral ash (r greater than 0.92, SEE less than 3.2 g). The bone mineral density (BMD, area density) of 3 lumbar vertebrae correlated accurately with the mean ash density of the vertebral body (r greater than 0.81, SEE less than 0.015 g/cm3). The so-called corpus density and central density determinations were less accurate. No difference in accuracy was found between measurements when using 3 mm and 4.5 mm step intervals. Variations in the distribution of mineral between the vertebral body and the posterior elements contribute to the error in predicting vertebral body mineral with DPA. QCT gave a smaller error when a cylindric portion of the vertebral body with a 20 mm diameter was measured compared with one with a 9 mm diameter, when the dual energy technique was used (p less than 0.01). With dual energy QCT a correlation was found between a center segment of 3 vertebrae in the lumbar spine and the mean ash density of the vertebral body of r = 0.92 (SEE = 0.010 g/cm3).(ABSTRACT TRUNCATED AT 250 WORDS)
The impact of diabetes was prospectively studied during a 5-year period in 428 unselected and consecutive patients with acute cerebrovascular disease of whom 18% were diabetic. Cerebral infarction was more frequent in diabetics (81 vs 70%, p less than 0.02) whereas transient cerebral ischaemia was less frequent (4 vs 14%, p less than 0.01). Case fatality rate during hospitalization was higher in the diabetic than in the non-diabetic patients (28 vs 15%, p less than 0.02). Patients who died during hospitalization, diabetic as well as non-diabetic, had significantly higher blood glucose concentrations on admission compared with patients who survived. Hematocrit values were higher in the diabetic than in the non-diabetic patients (p less than 0.02). Diabetics had higher systolic blood pressure levels than the non-diabetics in the acute phase (p less than 0.005). The diabetic stroke patients more often had a history of hypertension, atrial fibrillation, heart failure and angina pectoris than non-diabetics stroke patients and diabetic control patients without stroke. Stroke patients, not known to be diabetic, had larger mean oral glucose tolerance test curve areas when compared with healthy controls but not when compared with hospitalized controls. We propose that diabetes increases the risk for stroke through other concurrent risk factors, cardiac disorders in particular.
Albumin has been purified by chromatography using standardized procedures with different starting materials depending on previous fractionation. Plasma can be used directly after cryoprecipitation and Factor IX adsorption or after isolation of IgG. The plasma was centrifuged and then desalted on Sephadex G-25 Coarse, the pH was adjusted, and the euglobulins were precipitated before ion-exchange chromatography on DEAE- and CM-Sepharose CL-6B. This was followed by concentration by ultrafiltration, gel filtration on Sephacryl S-200, and final concentration and formulation. The albumin obtained was 99% pure and contained less than 1% of aggregated protein.