Biomedical subjects
Publications and source records attributed to H Olofsson.
It was recently suggested that the error with respect to experimental data in nuclear mass calculations is due to the presence of chaotic motion. The theory was tested by analyzing the typical error size. A more sensitive quantity, the correlations of the mass error between neighboring nuclei, is studied here. The results provide further support to this physical interpretation.
Studies on the hormonal regulation of bone metabolism in men have indicated covariation between insulin-like growth factor-I (IGF-I) and sex hormones with bone mineral density (BMD). In this study the relationships between BMD in total body, lumbar spine, femoral neck, distal and ultradistal (UD) radius and circulating levels of IGFs, IGF binding proteins (IGFBPs), and sex steroids were investigated in 55 Swedish men between 22 and 85 (52 +/- 18, mean +/- SD) years of age. BMD in total body, distal and UD radius, and femoral neck was positively correlated with serum IGF-I (r = 0.31 to 0.49), IGF-II (r = 0.32 to 0.48), IGFBP-3 (r = 0.37 to 0.53), and free androgen index (FAI) (r = 0.32 to 0.40), and negatively with IGFBP-1 (r = -0.37 to -0.41) and IGFBP-2 (r = -0.29 to -0.41) levels. A positive correlation was observed between BMD in femoral neck and estradiol/SHBG ratio (r = 0.34, P = 0.01). Age correlated negatively with serum IGF-I, IGF-II, IGFBP-3, FAI, estradiol/SHBG ratio, and BMD in total body, distal and UD radius, and femoral neck, and positively with IGFBP-1, IGFBP-2, and SHBG levels. According to stepwise multiple regression analyses, a combination of weight, IGFBP-3, and testosterone accounted for 43% of the variation in BMD in femoral neck, 34% in ultradistal radius and 48% in total body (P < 0.0001). These findings indicate that sex hormones and the different components of the IGF system are associated with BMD in Swedish men, suggesting that age-related changes in these systems could contribute to the development of osteoporosis in elderly men.
Free radicals have been shown to be involved in bone resorption in vitro and in rodents. We studied the effect of oxidative stress on bone mineral density (BMD) in 48 women and 53 men from a population-based study. The levels of 8-iso-PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and a control, 15-keto-dihydro-PGF(2alpha) (a biomarker of inflammatory response), were measured in urinary samples and their association with BMD and quantitative ultrasound (QUS) measurements were examined. In multivariate linear regression analyses, 8-iso-PGF(2alpha) levels were negatively associated with both BMD and QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2alpha). Our findings establish a biochemical link between increased oxidative stress and reduced bone density and provide a rational for further studies investigating the role of pro- and antioxidants in osteoporosis.
Today, cognitive impairment can be successfully treated with acetylcholine esterase inhibitors (AChE-I) in many, but not all, patients with Alzheimer's disease (AD). To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC scores (efficacy parameters) after 6 and 12 months of tacrine (an AChE-I) treatment were investigated in 145 AD patients. Of these, 84 were ApoE epsilon4-positive (ApoE4) and 61 were ApoE epsilon4-negative (ApoE2-3). No differences were found after 6 months of treatment, but after 12 months the CIBIC scores revealed that the ApoE4 patients had declined more than the ApoE2-3 patients (p < 0.05). No differences were found for the last 6 months of treatment. The results primarily suggest a faster rate of decline in the ApoE4 AD compared to the ApoE2-3, but may also reflect that ApoE epsilon4 genotype inheritance is a negative predictor of treatment effect of tacrine in AD patients.
BACKGROUND/AIMS: Insulin-like growth factor-I (IGF-I) levels are low in patients with chronic liver disease (CLD) and have been found to correlate with measurements of bone mineral density (BMD) in men with viral cirrhosis. The aim of this study was to investigate the relationship between circulating IGF-I levels and BMD in patients with CLD of other causes. METHODS: Fifty-eight patients with CLD were included. Age- and sex-matched normal individuals served as controls. Serum levels of IGF-I and IGF-II and their binding proteins (IGFBP-1-3) were measured by radioimmunoassay. BMD was measured by dual energy X-ray absorptiometry. RESULTS: IGF-I levels were 57+/-33 and 136+/-48 ng/ml; p<0.0001 in patients and controls, respectively. IGF-II and IGFBP-3 levels were lower (p<0.0001) and IGFBP-1 and IGFBP-2 levels were higher in patients compared with controls (p<0.0005 and p<0.0001, respectively). All growth factors, except for IGFBP-2, correlated with parameters of liver function. In a multiple regression analysis, adjusting for age, no correlation was found between IGF-I, IGF-II, IGFBP-1-3 and BMD in either patients or controls. CONCLUSION: Patients with CLD have low levels of IGF-I, IGF-II and IGFBP-3 that correlate with liver function. No relationship was found between low levels of growth factors and BMD.
BACKGROUND AND AIM: The pathophysiology of osteoporosis complicating chronic liver disease is unknown. Recent animal studies have found leptin to be a potent inhibitor of bone formation. The aim of this study was to investigate the relationship between serum leptin levels and bone mineral density in patients with chronic liver disease. METHODS: Fifty-eight patients, 39 females and 19 males, and age- and gender-matched controls were included. Bone mineral density was measured by using dual energy X-ray absorptiometry. Serum leptin was measured by using a radioimmunoassay. RESULTS: The mean serum leptin concentration was 10.4 +/- 11.3 and 15.2 +/- 17.9 ng/mL; P=0.11, in the patients and controls, respectively. Leptin correlated positively with body mass index in patients (r=0.40; P=0.003) and in controls (r=0.55; P < 0.0001). In patients classified as Child-Pugh grade B and C, serum leptin correlated negatively with bone mineral density in females at both the lumbar spine and the femoral neck (r=-0.78; P=0.04 and r=-0.86; P=0.03, respectively). In male patients, the correlation was only significant at the lumbar spine (r=-0.99; P=0.002 and r=-0.86; P=0.06, at the lumbar spine and femoral neck, respectively). No correlation was found between serum leptin and bone mineral density in the controls. CONCLUSION: An inverse relationship between serum leptin and bone mineral density was found in patients with advanced chronic liver disease. The reasons for these findings are uncertain, but a pathophysiological role of circulating leptin in osteoporosis in chronic liver disease is possible.
A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
The excretion of Eimeria oocysts, the faecal dry matter and the weight gain of three groups of 12 calves, were compared during their first 20 days of grazing on a pasture known to have been contaminated with oocysts of Eimeria alabamensis during the previous year. On the day of turnout (day 0) the calves in group 1 were each treated with one bolus per 200 kg bodyweight containing 1.6 g baquiloprim and 14.4 g sulphadimidine. The calves of group 2 received the same treatment on day 3, and the calves of group 3 were left untreated. Eleven of the untreated calves developed clinical coccidiosis due to E. alabamensis and excreted more than 850,000 oocysts/g of faeces 8-10 days after turnout. Seven of the calves in group 1 and five of those in group 2 developed diarrhoea, but it was milder and/or less persistent than in the untreated calves. The treated calves excreted significantly fewer oocysts and lost significantly less weight than the untreated calves. On day 21 all the calves were housed and on day 27 they were challenged with 10 million sporulated oocysts of E. alabamensis and turned out on to the same pasture. Only minor clinical signs were observed in some of the calves, indicating development of immunity in all groups. However, there was a tendency for the calves treated on day 3 to excrete more oocysts and to gain less weight than the other calves.
Twelve calves which had been immunised with a trickle dose of altogether 100,000 oocysts of Eimeria alabamensis 16 days before turnout and 12 uninoculated calves were monitored during their first 20 days of grazing on a pasture naturally contaminated with oocysts of E. alabamensis. Eleven of the uninoculated calves developed gruel-like diarrhoea 3-6 days after turnout and excreted more than 850,000 oocysts/g of faeces (OPG) a few days later. In contrast, none of the immunised calves developed clinical coccidiosis and most of them excreted only a few oocysts. They lost on average 18 kg less in bodyweight than the unimmunised control calves. On day 21 all the calves were rehoused and on day 27 they were challenged with 10 million sporulated oocysts of E. alabamensis and turned out onto the same pasture. Only insignificant clinical signs were observed in 2 of the immunised calves and in one of the control calves. It was concluded that immunisation is a promising control measure for E. alabamensis coccidiosis. However, fewer or attenuated oocysts must be used, as 9 of the 12 inoculated calves developed clinical coccidiosis before turnout as a result of the immunisation doses.
The complete spectra of Orion A and IRC +10216 in the range 72.2 to 91.1 GHz, obtained with the 20 m mm-wave telescope at the Onsala Space Observatory, are presented.
The spectra of the Orion KL molecular cloud and the envelope of the carbon star IRC+10216 have been surveyed at 1 MHz resolution over the interval 72.2-91.1 GHz to a sensitivity (in terms of main beam brightness temperature) usually better than 0.1 K. Some complementary data have been obtained at selected higher and lower frequencies. Detected lines are reported in Table 1. Approximately 170 lines from 24 known interstellar molecules were detected in Orion (Table 2); the corresponding numbers for IRC+10216 are 45 and 12, respectively (Table 3). Some 15 recombination lines of hydrogen (alpha, beta, gamma, delta) and helium (alpha) are also identified in Orion (Table 2). More than 100 of the Orion lines can be attributed to astronomically new transitions, the vast majority of which belong to only five species: SO2 (in total 17 lines), CH3CH2CN (19), CH3OH (16), (CH3)2O (21) and CH3OOCH (32). The rare occurrence of unidentified lines (5 definite lines in each object) is significant, possibly indicating that, in the case of Orion, the dominant chemical constituents are recognized. For IRC+10216 our results are less conclusive in this respect, partly due to the less effective excitation conditions in the envelope. We report (or confirm) the existence in these sources of several molecules which previously had only been found elsewhere: methylformate (CH3OOCH), isocyanic acid (HNCO), cyanodiacetylene (HC5N), vinyl cyanide (CH2CHCN), ketene (H2CCO) and probably the formyl radical (HCO) in Orion; and in IRC+10216 the first species containing the methyl group, methyl cyanide (CH3CN). The first astronomical detections of the isotopically rare species 34SO2 (Orion), and 29SiS and, tentatively, Si34S (IRC+10216) are also reported, as well as a number of newly identified high energy methanol lines. Multi-transition analysis of several molecular species is presented and gives information on physical conditions and chemical abundances in the Orion KL region (Tables 5 and 6). Gaussian decomposition of 0.25 MHz resolution profiles into "ridge", "hot core" and "plateau" emissions is used in an attempt to individually characterize these subregions. Striking chemical differences among the subregions emerge: (i) The estimated abundance ratios [SO, SO2, SiO]/[CO] are enhanced by a factor approximately > 100 in the plateau relative to the ridge, [HCN, HDO]/[CO] by a factor approximately > 10, while [HCO+, OCS, HNC, HC3N]/[CO] seem to be less enhanced in the plateau (by a factor approximately >10). (ii) The ratio of chemically saturated to unsaturated species differs markedly between the hot core and the ridge cloud (specifically HC3N vs. CH3CH2CN, and CH2CHCN) with the latter region more closely resembling both the cloud TMC-1 and IRC+10216. The chemical selectivity in the ridge cloud is very pronounced, with CH3OH as abundant as H2CO while (CH3)2O and CH3OOCH are an order of magnitude less abundant. We have neither detected CH3CH2OH and CH3COOH (acetic acid)--isomers of the two latter species, respectively--nor HCOOH, CH3CHO, or CH2CHCHO. H2C2O (ketene) is two orders of magnitude less abundant than H2CO. From the isotopic species of CH3OH, OCS, and HC3N we find 12C/13C approximately 40, in agreement with independent estimates by others and a factor of two lower than the solar system isotope ratio. The observed intensities of the hydrogen recombination lines are consistent with optically thin LTE emission, indicating that our He alpha/H alpha intensity ratio is relatively model independent and thus is an accurate measure of the helium abundance. We estimate a helium abundance by mass of 28 +/- 2%. The excitation conditions and relative abundances in the IRC+10216 envelope are reviewed. It is emphasized that the low detection rate of molecular lines in this object does not necessarily imply a poorer chemistry compared with that in interstellar clouds, but is partly a reflection of low abundances and unsatisfied excitation requirements. However, the CH3CN data indicate less favorable conditions for species containing methyl groups in this environment relative to interstellar clouds. The chemistry appears to be dominated by linear, especially unsaturated carbon-chain, molecules (Table 9). Rotational temperatures for HC3N and HC5N are estimated to be on the order of 15 K. Guided by the selective chemistry in IRC+10216 we tentatively assign two close doublets at 76.2 and 98.0 GHz to the radical C3H. In addition to Orion KL and IRC+10216 a few other sources have been observed, however in a less systematic way. We present selected data for W 51 M. The W 51 M methanol data, including newly identified high energy lines, indicate a rotational temperature of about 100 K.
Microwave radiation (2450 MHz CW) was tested for mutagenicity in Drosophila melanogaster. Embryos in water were exposed to the electromagnetic field with a mean specific absorption rate of 100 W/kg. A sensitive somatic test system was used, in which mutagenicity was measured as the frequency of somatic mutations for eye pigmentation. With the test system used, microwaves did not show any mutagenic activity.
Commercial petrol and two of its components, benzene and 1,2-dichloroethane, were tested for mutagenicity in Drosophila melanogaster. The chemicals were given to larvae through their food supply. A genetically unstable sexlinked test system caused by a transposable genetic element was used. Mutagenicity was measured by the frequency of somatic mutations for eye pigmentation. Commercial petrol and 1,2-dichloroethane showed mutagenic activity. With the system used, benzene did not show any mutagenic activity. The high frequency of mutations induced by 1,2-dichloroethane indicate the existence in Drosophila of a metabolic activating system.
Somatic eye-colour mutations in an unstable genetic system, caused by a transposable element in the white locus of the X-chromosome in Drosophila melanogaster, is suggested as an assay system for mutagenicity testing. The system is evaluated by comparison with a corresponding system in a stable X-chromosome. Its sensitivity is confirmed with X-ray and EMS treatment, and it is found to be confined to the specific segment of the X-chromosome where the transposable element is localized.
Vitamin B12 assimilation might be disrupted in patients with Alzheimer's disease. We therefore measured B12 carrier protein saturation and inactive B12 'analogues' in patients compared with healthy elderly individuals in a prospective case-controlled survey. Twenty-three patients, aged 60 or over, with features compatible with DSM-IV criteria for primary degenerative dementia of the Alzheimer type were recruited together with 18 cognitively intact age-matched control subjects. Total vitamin B12 (active corrinoids), holo- and apo-haptocorrin and transcobalamin were measured in serum. B12 analogues (inactive corrinoids) were estimated from the difference between R-binder-determined corrinoids and an intrinsic factor based B12 assay. Alzheimer patients had significantly lower active corrinoid than control subjects and the analogue/corrinoid ratio was significantly higher in the Alzheimer group. The inter-relationship between age, analogues and transcobalamin polarised patients into two distinct groups. Two disparate mechanisms might exist for the development of cerebral B12 deficiency in Alzheimer's disease, although both imply a disruption of selective B12 assimilation and analogue elimination in such patients.
The present study is a retrospective study of remoxipride therapy. A total of 103 patients, 65 years or older, with a DSM-III-R diagnosis of dementia or delirium, were included. They had all been treated with remoxipride because of psychotic symptoms or behavioural disturbances. The dose range of remoxipride was 50-300 mg, the median dose being 75 mg. The clinical effect was rated as good in two thirds of the patients, and side-effects were noted in one fourth. When psychomotor hyperactivity was the dominating problem, a good effect was rated in 81% of the patients. Side-effects were few and mild, the most common being tiredness; only 5 patients showed extrapyramidal symptoms.