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Biomedical subjects

Bo Nilsson

Publications and source records attributed to Bo Nilsson.

62 records · Page 4Linked to original sources

Transfer of prostasomal CD59 to CD59-deficient red blood cells results in protection against complement-mediated hemolysis.

PROBLEM: Prostasomes isolated from human seminal plasma have complement regulatory properties because of their content of CD59, a glycosylphosphatidylinositol (GPI)-anchored protein. We investigated a functional role of prostasomes by the possibility of transferring CD59 from prostasomes to rabbit erythrocytes (RE) and human erythrocytes obtained from patients with paroxysmal nocturnal hemoglobinuria (PNH), both types of cells lacking CD59. METHOD OF STUDY: We used the assay of hemolytic activity of the alternative pathway of the complement system to compare the liability of the erythrocytes to hemolysis by the complement system with and without pre-incubation with prostasomes. CD59 gained by the RE and PNH erythrocytes was established by flow cytometry. The effect of phosphatidylinositol phospholipase C (PIPLC) on the GPI anchor of prostasomal CD59 and the effect of heat treatment on the prostasomes were also studied. Anti-CD59 antibodies were used to block the protective effect of prostasomes on erythrocytes. RESULTS: Both RE and PNH erythrocytes showed diminished complement-mediated hemolysis after incubation with prostasomes. This was because of the transfer of CD59 from prostasomes to the red blood cells during pre-incubation as evidenced by the hemolytic assay and flow-cytometry. The efficacy of the prostasomes was affected by heat treatment and was totally lost at 100 degrees C. Phosphatidylinositol phospholipase C broke the GPI anchor and released CD59 from prostasomes and the RE surface (after pre-incubation with prostasomes) but not from the human PNH erythrocytes. CONCLUSIONS: A transfer mechanism of CD59 takes place during pre-incubation from prostasomes to erythrocytes lacking CD59 which supports the idea that transfer of prostasomal CD59 can protect cells from lysis elicited by C5b-9. This might be a mechanism by which autologous and allogeneic cells are protected against complement attack in the genital tracts.

Animals↗

Influence of body size and age on maximal diastolic velocity of mitral annulus motion.

BACKGROUND: Maximal long-axis relaxation velocity (RV(m)), measured from the mitral annulus motion (MAM), has recently been suggested as an index of left ventricular (LV) diastolic function. M-mode recording and pulsed tissue Doppler have been used. Regarding the M-mode method, reference values have not been presented previously. In the current study, therefore, the influence on RV(m) of such variables as age, body size, heart rate, and blood pressure was investigated to obtain adequate reference values. METHODS AND RESULTS: Fifty-seven healthy subjects were included in the study. RV(m) was recorded by M-mode echocardiography from apical 4- and 2-chamber views from 4 sites of the mitral annulus. Multiple regression analysis showed that heart rate ought to be taken into account when reference values are calculated for children and adolescents, and age must be considered in adults. For reference values in children and adolescents, the following equation is suggested: RV(m) = 171 - 0.54 x heart rate (SEE = 18.7). In adults over 18 years, the suggested equation is RV(m) = 163 - 1.29 x age (SEE = 8.4.)

Adolescent↗

Injuries in 8927 patients admitted after motor-cycle crashes in Sweden 1987-1994 inclusive.

OBJECTIVE: To discover morbidity and mortality rates after motor-cycle crashes on the national level in Sweden. DESIGN: Retrospective study. SETTING: Teaching hospital, Sweden. INTERVENTIONS: Extraction of data from International Classification of Diseases (ICD) codes E819C (motor-cycle drivers) and E819D (motor-cycle passengers) recorded in the Swedish Hospital Discharge Register (SHDR) between 1987 and 1994. MAIN OUTCOME MEASURES: Injury distribution, medical consequences, mortality, survival, and incidence by age, sex and geographical area. RESULTS: The number of people admitted to hospital after motor-cycle crashes decreased significantly during the period (from 1743 in 1987 to 1258 in 1994, p < 0.001). The most frequent injuries among drivers and passengers alike were fractures of the legs, arms, and vertebrae, followed by injuries to the head and brain. The in-hospital mortality was lower among drivers (n = 172, 2.2%) than among passengers (n = 31,3.3%). CONCLUSION: The incidence of injuries after motor-cyclist crashes decreased during the study period. The most common victims were young men with fractures and brain injuries. Those at most risk of dying were older passengers.

Accidents, Traffic↗

Injured moped riders who required admission to hospital in Sweden from 1987 to 1994.

OBJECTIVES: To find out the incidence, extent of injury, medical consequences, and mortality rate of moped riders involved in crashes in Sweden. DESIGN: Retrospective case study. SETTING: The Swedish Hospital Discharge Register (SHDR). SUBJECTS: 4716 moped riders, a total of 5857 admissions to Swedish hospitals from 1987-94. INTERVENTIONS: Statistical analysis of the Register. MAIN OUTCOME MEASURES: Incidence of injured moped riders in Sweden, mortality rate, types of injuries, and medical consequences. RESULTS: From 1987 to 1994, Swedish hospitals admitted 4716 moped riders (5857 admissions) injured in crashes, which corresponds to a mean of 8.5 injured/100 000 population a year. Of these 3993 were male (85%) and 723 female (15%), with a median age of 16 years (range 3-93). Twenty-four percent of those admitted to hospital spent more than a week there. The annual number of injured moped riders did not change significantly during this period. The total number of deaths in hospital was 59 (1%). Among those who died in hospital, 32 (54%) had head injuries, 16 (27%) fractures, and 5 (9%) abdominal or thoracic injuries. CONCLUSION: The number of injured moped riders in Sweden is low. Fractures of the extremities were most common, followed by injuries to the head and brain. The usual victim was a teenager or young man. Of the patients treated in hospital few died, most of whom were elderly men.

Accidents, Traffic↗

Cancer incidence among Swedish patients exposed to radioactive thorotrast: a forty-year follow-up survey.

Thorotrast is an alpha-particle-emitting radiological contrast medium that caused chronic exposure to internal alpha-particle radiation when it was administered systemically. Cancer incidence in 432 Swedish patients exposed to Thorotrast was evaluated by computerized linkage of the cohort with the Swedish Cancer Register. Standardized incidence ratios (SIRs) were calculated as the ratio of observed cases in the cohort to expected cases in the general population. A total of 170 cancers occurring in 152 individuals were reported, whereas only 57 cases were expected. The SIR was significantly increased for cancer at all sites (3.0), with the largest excesses noted for primary liver and gallbladder cancer (SIR = 39.2). Other significantly elevated risks were observed for liver cancer not specified as primary, small intestine cancer, stomach cancer, leukemia, kidney cancer, CNS tumors, and pancreatic cancer. Among women, there was a significantly increased risk for lung cancer, based on a small number. Our results show that cumulative radiation exposure is directly related to carcinogenesis in the liver and gallbladder, which is consistent with earlier findings. In addition, there may be a relationship between radiation exposure and the development of other solid tumors.

Adolescent↗

Inhibition of thrombin abrogates the instant blood-mediated inflammatory reaction triggered by isolated human islets: possible application of the thrombin inhibitor melagatran in clinical islet transplantation.

A thrombotic/inflammatory reaction is elicited when isolated islets of Langerhans come in contact with ABO-compatible blood. The detrimental effects of this instant blood-mediated inflammatory reaction (IBMIR) provide a reasonable explanation for the observation that an unexpectedly high number of islets, from several donors, are needed to produce normoglycemia in transplant patients with type 1 diabetes. In this study, the hypothesis that a specific thrombin inhibitor, Melagatran, could reduce IBMIR in an in vitro model in which human islets are exposed to ABO-compatible blood was tested. The administration of Melagatran abrogated IBMIR dose-dependently. Islets exposed to blood, in the absence or presence of 0.4 micromol/l Melagatran, exhibited a loss of integrity and were found to be trapped in macroscopic clots containing platelets and CD11b(+) leukocytes. At concentrations from 1 to 10 micromol/l, Melagatran inhibited both coagulation and complement activation. Also, platelet and leukocyte activation and consumption were decreased. Islet morphology was maintained with almost no platelets adhering to the surface, and infiltration by CD11b(+) leukocytes was considerably reduced. In conclusion, Melagatran significantly reduced IBMIR in this model system. This protective effect indicates that thrombin plays a pivotal role in IBMIR and suggests that thrombin inhibition can improve the outcome of clinical islet transplantation.

ABO Blood-Group System↗

Incidence of uveal melanoma in Sweden from 1960 to 1998.

PURPOSE: To investigate the incidence of uveal melanoma in Sweden during the period from 1960 to 1998, with respect to age distribution, gender, and changes in incidence over time. METHODS: The Swedish Cancer Registry was searched for patients with uveal melanoma and cross-checked against hospital files over patients where an eye-sparing treatment had been applied, to ensure inclusion in the Registry even when no histologic specimen was available. The crude and age-standardized incidence was estimated separately for each gender. The Swedish population of 1970 to 1974 was used as a standard, and the annual change in incidence was calculated by using a regression model with logarithmic incidence numbers. RESULTS: In total, 2997 patients met the criteria, of whom 1542 were males and 1455 females. During the 39-year period, the age-standardized incidence of uveal melanoma declined significantly in the male population, from 11.7 cases/million to 8.4 cases/million (P = 0.002). The trend toward reduced incidence in females, from 10.3 to 8.7 cases/million did not reach statistical significance (P = 0.108). The annual relative change in incidence was 1% (95% CI, 0.8%-1.2%) in males and 0.7% (95% CI, 0%-1.3%) in females. The age-specific incidence revealed a significantly higher incidence among men older than 45 years (23.5 cases/million) compared with the incidence in women of the same age group (19.2 cases/million; P < 0.001). CONCLUSIONS: A Swedish national survey performed to establish the incidence of uveal melanoma during the period from 1960 to 1998 revealed a decreasing incidence in the male and a stable incidence in the female population.

Adolescent↗

The recent finding that tissue factor is produced by the pancreatic islets constitutes a possible link between insulin resistance and cardiovascular disease.

Approximately 70% of the patients admitted to the hospital with an acute myocardial infarction have type 2 diabetes mellitus or impaired glucose tolerance (IGT). Insulin resistance with compensatory hyperinsulinemia is a feature that is common to both type 2 diabetes and IGT. Increased risk of coronary heart disease (CHD) in conditions characterized by insulin resistance has been associated with hyperinsulinemia and hyperproinsulinemia. As indicated in several studies, there exists a connection between postprandial hyperinsulinemia/hyperglycemia and activation of the coagulation cascade. The recent finding that tissue factor (TF) is produced and secreted by the alpha and beta cells of the islets of Langerhans maybe the link between these 2 conditions. The local production of TF in human islets and excretion of microparticle-bound or alternatively spliced soluble TF in response to prolonged periods of hyperglycemia provide a tentative explanation for the activation of the TF pathway during hyperinsulinemia. Here we review the field and set forth a hypothesis that links TF expression in the islets of Langerhans to the increased risk of CHD.

Blood Coagulation↗