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Biomedical subjects

J A Nilsson

Publications and source records attributed to J A Nilsson.

At least 19 recordsLinked to original sources
PubMed2006

Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis.

p18(Ink4c) functions as a dedicated inhibitor of cyclin-D-dependent kinases. Loss of Ink4c predisposes mice to tumor development and, in a dose-dependent manner, complements the tumor-promoting effects of various oncogenes. We have now addressed whether Ink4c loss impacts B-cell tumor development in the Emu-Myc transgenic mouse, a model of human Burkitt lymphoma. Loss of one or both alleles did not influence the onset of lymphoma in Emu-Myc transgenics, and did not appreciably affect Myc's proliferative or apoptotic responses in precancerous B cells. Nevertheless, Ink4c loss modulated the effects of Myc-induced transformation by decreasing the frequency of Arf loss, an ordinarily common event in Emu-Myc-induced lymphomas.

Animals↗
PubMed2004

Alcohol dehydrogenase 3 transcription associates with proliferation of human oral keratinocytes.

Gene expression underlying cellular growth and differentiation is only partly understood. This study analyzed transcript levels of the formaldehyde-metabolizing enzyme alcohol dehydrogenase 3 (ADH3) and various growth and differentiation-related genes in human oral keratinocytes. Culture of confluent cells both with and without fetal bovine serum inhibited colony-forming efficiency and induced a squamous morphology. Confluency alone decreased the transcript levels of ADH3, the proliferation markers cell division cycle 2 (CDC2) and proliferating cell nuclear antigen (PCNA), and the basal cell marker cytokeratin 5 (K5), but increased transcripts for the suprabasal differentiation markers involucrin (INV) and small proline-rich protein 1B (SPR1). These changes were variably influenced by serum, i.e., loss of CDC2 and PCNA was inhibited, loss of K5 promoted, increase of SPR1 transcripts inhibited, and increase of INV promoted. The extent and onset of the effects implied that ADH3 transcription serves as a proliferation marker and that confluency with or without serum exposure can serve to selectively analyze proliferative and differentiated cellular states.

Aldehyde Oxidoreductases↗
PubMed2001

Sleep disturbance in association with elevated pulse rate for prediction of mortality--consequences of mental strain?

OBJECTIVES: Sleep deprivation has experimentally been shown to adversely influence glucose metabolism, endocrine function and sympathovagal balance in young men without known serious disease. We investigated the impact of sleep problems and resting heart rate in a large sample of self-reported, healthy middle-aged men and women on long-term mortality. METHODS: In all 22,444 men and 10,902 women participated in a population-based health screening (71% mean attendance), including blood sampling and examination of blood pressure (BP) and pulse rate after 10 min supine rest, as well as a self-administered questionnaire on sleep problems. Mortality was assessed from national death registers. RESULTS: Sleep disturbances were related to increased cardiovascular risk factor levels at baseline in both sexes, and predicted total and cause-specific mortality after a mean of 12 years (women) and 17 years (men) of follow-up. In men, self-reported healthy at baseline, total mortality during follow-up was independently predicted by both sleep problems and increased resting heart rate, also after adjustment for smoking, body mass index (BMI), systolic BP, cholesterol, smoking and problematic alcohol drinking habits. A step-wise increased total mortality was shown in men reporting successively worse sleep problems and higher heart rate, highest hazard ratio 2.7 [95% confidence interval (CI) = 2.1-3.4] after adjustments, compared with men free from sleep problems and with normal heart rate. CONCLUSIONS: Sleep disturbance is a predictor of total and cause-specific mortality in both sexes, but only interacts with increased resting heart rate for this prediction in healthy men. Sleep problems correlated cross-sectional with disturbances in lipid and glucose metabolism, even after adjustment for degree of obesity and smoking. Sleep disturbance is a symptom for a biological pathway that is correlated to premature mortality. One possible explanation would be that it acts in concert with sympathetic nervous activation (SNA), both being consequences of chronic stress exposure.

Analysis of Variance↗
PubMed2001

On difficulties in diagnosing deep vein thrombosis in daily clinical work and research practice.

This article enlightens the diagnostic difficulties when performing and interpreting a phlebography or color Doppler ultrasonography (CDU), which may have serious consequences in the daily clinical and laboratory work. In laboratory research as well as in clinical trials the most fundamental principle is to obtain a correct diagnosis. Less than 50% of patients with deep venous thrombosis (DVT) manifest the classical symptoms and signs of DVT and consequently the diagnosis is based upon methods such as phlebography or CDU. Some veins are especially hard to display, i.e. the veins of the planta pedis, the deep muscle veins of the calf and thigh and the deep internal iliac vein. Thus, the ideal diagnostic method must display the whole venous system from the planta pedis to the caval vein. A false negative examination puts the patient at risk of pulmonary embolism, which may present with a sudden onset and fatal outcome. A venous dysfunction as well as recurrent DVT will also be a continuous risk factor. A false positive interpretation may result in unnecessary anticoagulation treatment and bleeding complications. The combination of phlebography and CDU together with the strict use of a scoring method will increase the possibility of a proper diagnosis focusing on the diagnostically difficult areas of the venous system.

Clinical Laboratory Techniques↗
PubMed2000

Expression of alcohol dehydrogenase 3 in tissue and cultured cells from human oral mucosa.

Because formaldehyde exposure has been shown to induce pathological changes in human oral mucosa, eg, micronuclei, the potential enzymatic defense by alcohol dehydrogenase 3 (ADH3)/glutathione-dependent formaldehyde dehydrogenase was characterized in oral tissue specimens and cell lines using RNA hybridization and immunological methods as well as enzyme activity measurements. ADH3 mRNA was expressed in basal and parabasal cell layers of oral epithelium, whereas the protein was detected throughout the cell layers. ADH3 mRNA and protein were further detected in homogenates of oral tissue and various oral cell cultures, including, normal, SV40T antigen-immortalized, and tumor keratinocyte lines. Inhibition of the growth of normal keratinocytes by maintenance at confluency significantly decreased the amount of ADH3 mRNA, a transcript with a determined half-life of 7 hours. In contrast, decay of ADH3 protein was not observed throughout a 4-day period in normal keratinocytes. In samples from both tissue and cells, the ADH3 protein content correlated to oxidizing activity for the ADH3-specific substrate S:-hydroxymethylglutathione. The composite analyses associates ADH3 mRNA primarily to proliferative keratinocytes where it exhibits a comparatively short half-life. In contrast, the ADH3 protein is extremely stable, and consequently is retained during the keratinocyte life span in oral mucosa. Finally, substantial capacity for formaldehyde detoxification is shown from quantitative assessments of alcohol- and aldehyde-oxidizing activities including K:(m) determinations, indicating that ADH3 is the major enzyme involved in formaldehyde oxidation in oral mucosa.

Aldehyde Oxidoreductases↗
PubMed2000

Long-term outcome of the Malmö preventive project: mortality and cardiovascular morbidity.

OBJECTIVES: To analyse the effects on mortality and cardiovascular morbidity in a population-based sample, invited to an intervention programme incorporating a baseline screening examination and treatment programmes for subjects with cardiovascular risk factors, high alcohol intake and, in women, suspicion of breast cancer on mammography. SETTING: Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. SUBJECTS: Birth cohorts (aged 32-51 years) invited to screening examination (men = 9. 923; women = 4.422) were compared to birth cohorts not invited (men = 6.655; women = 4.290). Mean participation rate in the invited cohorts was 71% (range 64-78%). SCREENING EXAMINATION: Between 1974 and 1992 a baseline screening including a physical examination, blood pressure, a questionnaire regarding, e.g. family history, lifestyle, and socio-economic factors, laboratory tests of serum cholesterol, triglycerides, gamma-glutamyl-transferase, blood glucose before and after an oral glucose load, as well as a mammography examination in women, was performed. INTERVENTIONS: Subjects with hypertension; hyperlipidaemia; diabetes or glucose intolerance; high alcohol intake; or, in women, suspicion of breast cancer were referred to special outpatient clinics. MAIN OUTCOME MEASURES: Total and cause-specific mortality, nonfatal myocardial infarction, and stroke, from the screening examination until the end of 1995, was followed in both the intervention and control groups, using national and/or local registries. RESULTS: Total mortality did not differ significantly between the intervention group and control group. Cause-specific deaths were also similar except for 'other' deaths amongst men being significantly lower in the intervention group, mainly due to a lower mortality from 'other' causes (suicide, alcohol related deaths) in men under 40 years of age at baseline. Women under 40 years of age had a significantly lower mortality from cancer in the intervention group than in the control group. Nonfatal myocardial infarction and stroke did not differ between intervention and control group in either sex. Within the invited birth cohorts, nonparticipants had a higher total and cause-specific mortality. CONCLUSIONS: Risk factor screening for major diseases such as cardiovascular disease, alcohol abuse, diabetes mellitus and breast cancer, and subsequent treatment of the detected risk factors/diseases - The Malmö Preventive Project - did not reduce total mortality in the intervention group as a whole. In subjects under 40 years of age at entry, total mortality was lower in the intervention group than in the control group. In men, this seemed to be due to a reduction of alcohol-related deaths, whilst in women death from cancer was reduced.

Adult↗
PubMed2000

Location and extent of deep vein thrombosis in patients with and without FV:R 506Q mutation.

Resistance to activated protein C due to FV:R 506Q mutation is the most common known genetic risk factor for deep leg vein thrombosis (DVT). The aim of this prospective study was to describe and compare the location and extent of DVT, reflected by a scoring system, in a group of patients with and without FV:R 506Q mutation. Of 247 consecutively included patients undergoing phlebography 105 had a DVT, 36 (35%) in the FV:R 506Q mutation group and 69 (65%) in the non-FV:R 506Q mutation group. Compared to the non-FV:R 506Q mutation group there was a significant increase in the incidence of DVT in the FV:R 506Q mutation group (p = 0.041, OR = 1.79 [1.02-3.15]), a significantly lower mean DVT score of the iliofemoral vein segments (p = 0.0081) and a significantly lower incidence of DVT in the iliofemoral vein segments (p = 0.007, OR = 10.6 [1.3-83.3]), 1/36 (2.8%) compared to 16/69 (23.2%). As controls 288 blood donors were included, with and without FV:R 506Q mutation and with no history of DVT in order to evaluate risk factors of DVT. The odds ratio of an iliofemoral DVT was 0.5 ([0.06-3.90), p = 0.50]) when FV:R 506Q mutation was present, compared to the control group, and at locations below the iliofemoral segments 5.28 ([3.01-9.28], p = less than 0.0001). Our findings provide the basis of a detailed phlebographic description and for the first time, to our best knowledge, shows a specific phlebographic pattern that may be linked to an inherited hypercoagulable state.

Activated Protein C Resistance↗
PubMed1999

Incidence of hip fractures in Malmö, Sweden, 1992-1995. A trend-break.

The incidence of hip fractures in Malmö, Sweden, has been studied since 1924. Predictions based on material from the 1950s to the 1980s have shown an almost exponential increase in incidence. During 1992-1995, 2,268 patients aged 50 and older, with hip fractures, were admitted to Malmö University Hospital, the only hospital in the city treating hip fractures. 76% were women with a mean age of 81 (SD 8) years, and the mean age of men was 78 (SD 9) years. 47% of the fractures were cervical. The annual incidences per 10,000 inhabitants were 36 in men and 85 in women. The corresponding numbers of subjects over 80 years were 170 men and 297 women. These findings show that the incidence is no longer increasing. The causes of such a trend-break could be successful osteoporosis prevention, an increasing proportion of non-Scandinavian immigrants with a lower genetic risk of osteoporotic fractures, or a healthier elderly population. Increasing number of the population at risk already have two operated hips, due to previous fractures or arthrosis. Other causes may be fewer prescriptions of sedatives and higher winter temperatures.

Age Distribution↗
PubMed1998

Formation of DNA adducts in human buccal epithelial cells exposed to acetaldehyde and methylglyoxal in vitro.

Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes, present in the environment and endogenously formed in animals and humans. They have both been shown to readily form DNA adducts under simulated physiological conditions. We report here on the use of cultured normal and SV40T antigen-immortalized human buccal epithelial cells as model systems for aldehyde exposure of the oral epithelium, occurring through the ingestion of alcoholic beverages and brewed coffee, as well as by inhalation of tobacco smoke and automobile exhaust. By the application of recently developed 32P-postlabeling methods, the presence of both endogenous and induced AA and MG DNA adducts was demonstrated in cultured human epithelial cells. Furthermore, these DNA adducts were formed in a dose-dependent manner at aldehyde concentrations that were relatively nontoxic to the cells.

Acetaldehyde↗
PubMed1998

Are annual fluctuations in hip fracture incidence dependent upon the underlying mortality rate?

There is substantial variation in hip fracture incidence rates from one year to the next. To determine whether this is related to varying mortality rates in the underlying population, we carried out an ecological analysis in Rochester and Olmsted County, Minnesota. In a given year, mortality in the general population was not related to hip fracture incidence nor did the fracture incidence rates influence the overall death rate. There was a negative correlation between hip fracture incidence and mortality in the preceding year among women, but not men; the trend was statistically significant among women less than 80 years of age. Both cervical and intertrochanteric hip fractures in women had a similar relationship to mortality in the population the year before. There was no consistent relationship between hip fracture incidence and mortality rates two or three years previously. Although many hip fractures occur in frail individuals near the end of life, patterns of mortality in the underlying population cannot account for the annual variation in hip fracture incidence.

Aged↗
PubMed1998

Toxicity of formaldehyde to human oral fibroblasts and epithelial cells: influences of culture conditions and role of thiol status.

The toxicity of formaldehyde, a monomer released from certain polymeric dental materials, was studied in cultured human oral fibroblasts and epithelial cells. The influences of growth conditions were evaluated for both cell types, as well as the role of the internal and external thiol states. A one-hour exposure to formaldehyde decreased the colony-forming efficiency (CFE) of both cell types in a concentration-dependent manner, although the toxicity varied up to 100-fold with the conditions. Clearly, the presence of serum and the thiol cysteine counteracted the toxicity in fibroblasts. Similarly, pituitary extract and cysteine, or a mixture of amino acids and ethanolamines, counteracted the formaldehyde toxicity in serum-free cultures of epithelial cells. In contrast, a growth-promoting surface matrix of fibronectin and collagen did not influence the formaldehyde toxicity, as shown by both the CFE assay and a dye reduction assay. Further, a short-term change to the various growth media per se with or without the supplements serum or cysteine did not significantly alter the CFE. Analysis of the thiol state demonstrated significant differences between epithelial cells and fibroblasts, i.e., comparatively lower cellular levels of the free low-molecular-weight thiols glutathione and cysteine in fibroblasts. This result correlated to significantly higher formaldehyde toxicity in the fibroblasts than in the epithelial cells. Taken together, the results indicated the cytoprotective function of both intracellular and extracellular thiols toward formaldehyde, as well as the usefulness of thiol-free and chemically defined conditions for toxicity assessments in oral epithelial cells and fibroblasts. We conclude that the combined use of a controlled external milieu and the presumed target cell type may be advantageous in evaluations of oral toxicity mechanisms or the toxic potency of dental materials, particularly those which, like formaldehyde, may react with thiols or amines.

Biological Assay↗
PubMed1997

A problem-based education program for patients with rheumatoid arthritis: evaluation after three and twelve months.

OBJECTIVE: To develop and evaluate the effect of a new arthritis education program based on a previous study. METHODS: One hundred individuals with established rheumatoid arthritis randomized to an intervention group or a control group completed self-report questionnaires. RESULTS: Three months after the education program the patients in the intervention group had increased their knowledge about their disease. They reported increased practice of exercise and joint protection and reduction of disability and pain. After 12 months, increased knowledge and practice of joint protection was maintained. However, there was no longer any difference between the intervention group and the control group regarding reported pain, disability, and practice of exercise. At both intervals the individuals in the intervention group reported an increased ability to handle their pain and a reduction of problems with their disease. The control group remained stable except for a slight increase in pain. CONCLUSION: A structured patient education program had positive impact for 3 months, and some improvements were maintained for 12 months. We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis.

Activities of Daily Living↗
PubMed1996

Changes of bone mineral mass and soft tissue composition after hip fracture.

The aim of this prospective longitudinal study was to measure prospectively the bone mineral density (BMD) and anthropometric variables after a hip fracture. In particular, we studied changes in the BMD in both the injured and uninjured hips, and examined if the postoperative mortality rate and complications, including pseudarthrosis of the fracture and late segmental collapse of the head of the femur, could be predicted by early bone mass measurements. The bone mineral density and the body composition were measured with dual energy X-ray absorptiometry in 102 consecutive hip fracture patients, 31 men and 71 women, with a mean age of 74 and 79 years, respectively. All cases were operated on within 3 days. The measurements were undertaken within 10 days after the fracture, after 4 and after 12 months. The BMD of the hip fracture cases decreased, especially in the lower extremities where the patients lost 7%, during the first year after the fracture. The patients also lost lean body mass (5%) but gained fat (11%) during the same period. They lost significantly more bone mass in the fractured hip than in the uninjured hip (p < 0.05). No difference was found between those patients who survived and those who died within 2 years after their hip fracture in neither the initial measurement nor in the follow-up measurements. Also, we found no difference between those patients whose hip fracture healed and those who developed late segmental collapse or pseudarthrosis. In conclusion, osteoporotic hip fracture cases lose bone mass at an increased rate, especially in the fractured hip. Also, their soft tissue composition changes, gaining fat while losing muscle mass. Furthermore, it seems that early bone mineral measurements cannot predict postoperative failures or postoperative mortality.

Aged↗
PubMed1996

Cardiovascular risk groups and mortality in an urban swedish male population: the Malmö Preventive Project.

OBJECTIVES: To describe the size, overlap and mortality of four cardiovascular risk groups, in order to give a scientific background for the prevention of cardiovascular disease in a representative urban population. SETTING: Section of Preventive Medicine, Department of Medicine, Malmö University Hospital, Malmö, Sweden. SUBJECTS: Between 1974 and 1984 22444 men born between 1949 and 1921, constituting 75% of the total male population in these age groups, took part in a comprehensive screening examination aimed at detecting risk factors for cardiovascular disease. INTERVENTIONS: Those at high-risk of developing cardiovascular disease were referred to their general practitioner or to special clinics for hypertension, hyperlipidaemia and diabetes. The follow-up, which lasted until the end of 1991, averaged 12.2 years. MAIN OUTCOME MEASURES: Total death (n = 1450) and death from ischaemic heart disease (IHD) (n = 471). RESULTS: Hypertension was found in 13%, hypercholesterolaemia in 19% and diabetes mellitus in 2.6% of the subjects; 49% of the subjects smoked. Multiple risk factors were found in over 17% of the total cohort. Despite the intervention, all-cause mortality during follow-up was increased three-fold in smokers and in men with hypercholesterolaemia, four-fold in hypertensive men and five-fold in men with diabetes, compared to men with no risk factors. The vast majority of deaths (81%) occurred in men who smoked, had hypertension or had high serum cholesterol. Ischaemic heart disease (IHD) was increased five-fold in smokers, seven-fold in men with hypercholesterolaemia, nine-fold in hypertensive men and 12-fold in men with diabetes. Again, the vast majority of IHD deaths (86%) occurred in the first three categories. Combinations of risk factors substantially increased total mortality as well as IHD mortality. CONCLUSIONS: The large proportion (64%) of the population with risk factors for cardiovascular disease and the substantially (5-12-fold) increased IHD mortality in those risk groups, calls for actions aimed at preventing premature IHD deaths. Such action should include measures directed towards the whole population and comprehensive treatment programmes for high-risk individuals, including intervention to stop smoking. The substantial overlap between risk factors calls for one high-risk clinic caring for all risk groups.

Adult↗
PubMed1996

Cardiovascular risk factors in commercial flight aircrew officers compared with those in the general population.

Cardiovascular disease is the most common reason for loss of license among commercial flight pilots. This study was done to explore cardiovascular risk factors among aircrew officers. The study group consisted of 113 male commercial flight aircrew officers (aviators), aged thirty-five to forty-four years (mean: 38.8 years) who participated in the compulsory health screening. Men investigated at the Health Screening Centre, Malmö, were used as the reference group. Group 1, for ECG, (n 771), aged thirty-eight to forty-four years (mean: 42.1). Group 2, for height, weight, body mass index (BMI) (weight kg/height m2), blood pressure, serum cholesterol (total), and smoking habits (n 5005), aged thirty-five to forty-four years (mean: 39.2). The aviators did not differ from the reference population in regard to height, weight, BMI, diastolic blood pressure, or smoking habits. However, the incidences of electrocardiographic left ventricular hypertrophy, increased systolic blood pressure, and the level of cholesterol were significantly higher in the aviators when compared with the controls. Aircrew members may primarily be selected by criteria that differ from the male population in general. Excessive environmental stress, ie, shift work, jet lag, fatigue, as well as dietary factors, may also contribute to anomalies in the group. The clinical consequences of these anomalies for the aviators should be further evaluated, for they are important both for the aviators and for flying safety.

Adult↗
PubMed1994

Serum beta-hexosaminidase isoenzymes are related to risk factors for atherosclerosis in a large population of postmenopausal women.

Lysosomes are involved in atherogenesis. Therefore we have studied the level of serum beta-hexosaminidase isoenzymes (Hex A and Hex B) in relation to risk factors for atherosclerosis in a homogeneous population of 886 post-menopausal women. We found a relation with several risk factors such as serum triglycerides, diastolic and systolic blood pressure, blood glucose, waist/hip ratio and body mass index but not with serum cholesterol. Also, the mean values for Hex A and Hex B were higher in smokers than in non-smokers but only the mean value for Hex A differed significantly. The relation of serum beta-hexosaminidase isoenzymes to risk factors might be due to lysosomal over-loading, which gives rise to increased enzyme synthesis and enhanced secretion of lysosomal enzymes to circulation. The subjects in the 95-100 percentile of Hex A showed significantly increased frequency of myocardial infarction of their fathers and of stroke in their mothers and the subjects in the 95-100 percentile of Hex B showed increased frequency of stroke in their mothers. Thus the findings of a relation between Hex isoenzymes and heredity for vascular disease further stress the significant relation between Hex isoenzymes and risk factors. Since Hex B is a sensitive marker for alcohol abuse, we also investigated its serum level in subjects that could be suspected of alcohol abuse. However, we did not find any differences in these subjects compared with the others, possibly due to the relatively short half-life of Hex B after alcohol withdrawal.

Alcoholism↗