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Biomedical subjects

K Olsson

Publications and source records attributed to K Olsson.

At least 37 records · Page 2Linked to original sources

Impact of polychlorinated naphthalenes (PCNs) in juvenile Baltic salmon, Salmo salar: evaluation of estrogenic effects, development, and CYP1A induction.

Juvenile Baltic salmon, Salmo salar, were fed commercial salmon food contaminated with different concentrations of polychlorinated naphthalenes (PCNs; 0.1, 1, 2, or 10 microg PCN/g food). Among other effects, possible estrogenic impact caused by PCNs were evaluated. Fish were therefore fed a diet contaminated with 17beta-estradiol (E2; 0.94 or 9.4 microg E2/g food), as a positive control. After 8, 13, 17, and 41 weeks, sampling took place. Growth, liver somatic index (LSI), EROD activity, and vitellogenin content in blood plasma were measured along with morphological studies of gonads and chemical analyses to determine the effects caused by PCNs. Exposure to PCNs did not seem to have any effects on body weight gain, since the group fed the high dose followed the growth in the control group during the entirely experimental period. After 41 weeks of exposure the groups fed 2 and 10 microg PCN/g food had significantly lower LSIs compared with the control, indicating liver toxic effects of PCNs. Furthermore, a dose-dependent induction of EROD activity was found. At week 41, the control group had an activity of 4.9 +/- 4.8 pmol/mg prot/min, whereas it was between 69 +/- 21 and 720 +/- 370 pmol/mg prot/min in the exposed groups, respectively. Examination of gonadal morphology showed that PCNs also had negative effects on ovaries in Baltic salmon, including delayed development. The distribution between females and males, gonadal morphology, and vitellogenin content in blood plasma did, however, indicate that PCNs are not capable of causing effects similar to E2 or xenoestrogens. Exposure to both of the concentrations of E2 resulted in decreased body weight gain, increased LSI, and feminization of the gonads. E2 did, however, not induce any EROD activity.

Animals↗

Real-time t(11;14) and t(14;18) PCR assays provide sensitive and quantitative assessments of minimal residual disease (MRD).

Non-Hodgkin's lymphoma (NHL) arises as a clonal transformation of normal B and T cell differentiation and is often characterized by a higher incidence of specific chromosomal translocations. We have developed real-time TaqMan PCR assays directed toward two of these tumor-associated DNA markers, the t(14;18)(q32;q21.3) at the major breakpoint region of the bcl-2 gene and the t(11;14)(q13;q32) at the bcl-1 major translocation cluster. During analysis of serial dilutions of t(14;18)-positive DNA, the t(14;18) real-time PCR was at least as sensitive as nested PCR and demonstrated enhanced quantitative potential. Moreover, in a blinded comparison of the t(14;18) real-time PCR and a clinically validated nested PCR protocol using 134 cell line and patient DNA samples, the real-time PCR detected the translocation in 30.0% more cases than nested PCR. Both the t(14;18) and t(11;14) real-time PCR assays were used to quantitate minimal residual disease (MRD) in an NHL clinical trial assessing the safety and efficacy of a tumor-purging protocol in autologous stem cell transplantation. The assays were also used to evaluate disease depletion in an ex vivo tumor spiking model in which normal peripheral blood was spiked with tumor cell lines and processed according to the clinical purging method. PCR data from both the clinical trial and the ex vivo model demonstrated a 4 to 6 log reduction in tumor cells during CD34+ and CD34+ Thy-1+ enrichment. Because the t(14;18) and t(11;14) real-time PCR assays are very sensitive, quantitative, rapid, and require no post-PCR manipulation, they may serve as practical alternatives to nested PCR.

Antigens, CD34↗

Telemetric registration of heart rate and blood pressure in the same unrestrained goats during pregnancy, lactation and the non-pregnant, non-lactating period.

The purpose of this study was to investigate how changes in heart rate and arterial blood pressure relate to the time of day, reproductive period and feeding routines in dairy goats (Capra hircus). Registrations were made by radiotelemetry in the same four goats during pregnancy, lactation and the non-pregnant, non-lactating (dry) period. Heart rate rose around the morning and afternoon feedings, whereas blood pressure did not show any diurnal rhythm. Comparison between reproductive periods revealed that heart rate was higher during the fifth month of pregnancy than during lactation and the dry period, whereas for blood pressure no such differences between periods were found. Withholding three meals from lactating goats resulted in a continuous slowdown of the heart rate, whereas blood pressure fluctuated. Re-feeding temporarily increased the heart rate but had no effect on blood pressure which continued to fluctuate. After another 2 days, blood pressure (but not heart rate) had stabilized. Food-restriction, aimed at terminating milk production resulted in a consistently depressed heart rate and reduced the mean and systolic blood pressures at night. The results show that with this implantable telemetry device it is possible to measure both heart rate and blood pressure day and night in the same unrestrained animals over a length of time long enough to include all reproductive periods. Our results emphasize that when planning experiments it is important that the exact stage in each reproductive period, the act of feeding and the amount of food given be taken into account.

Animals↗

Changes in airway dead space in response to methacholine provocation in normal subjects.

Measurements of bronchial hyper-responsiveness rely on sensitive techniques for measurement of bronchoconstriction, ideally based on tidal breathing. A potentially useful technique is measurement of airway dead space (VDaw), which reflects the volume of the conducting airways. The aim of this study was to evaluate measurements of VDaw with the single breath test for CO2 (SBT-CO2), compared to spirometric measurements, as a method of measuring bronchial response to methacholine challenge. Nineteen healthy adults were studied. Dosimetric methacholine challenge tests were performed on two study days. Forced expirations or the SBT-CO2 were used to assess the response. There were dose-dependent reductions in the spirometric measurements, with a 10 +/- 10% reduction from the baseline value of forced expiratory volume at the highest dose of methacholine. There was a dose-dependent reduction from the baseline value of VDaw by 19 +/- 9% at the highest dose. There was also a dose-dependent increase in the slope of the alveolar plateau of the SBT-CO2. This study provides support for measurement of VDaw as a means of evaluating bronchial responsiveness after methacholine challenge. In a group of healthy adults, this method shows a greater response but with similar dispersion as measurement of forced expiratory volume after methacholine challenge.

Adolescent↗

Hormonal changes during parturition in heifers and goats are related to the phases and severity of labour.

Parturition is a natural event that involves stress and pain for the mother. We thus hypothesized that levels of stress hormones measured during parturition could reflect levels reached in response to severe discomfort and pain of other kinds as well. The aim of this study was therefore to determine whether plasma concentrations of cortisol, adrenaline, noradrenaline, beta-endorphin, met-enkephalin, vasopressin and oxytocin vary depending on the phase and severity of labour in dairy heifers (ten) and dairy goats (six), and how these hormones interact with each other. Blood samples were taken once a day for 3 days before labour and for 3 days afterwards and at predetermined phases during labour. All heifers delivered one calf and five of them needed obstetrical assistance. Two of the goats delivered one kid, and four had twins; all kidded without help. The cortisol concentration peaked when the calf and the first kid were born. In the heifers, plasma adrenaline increased after delivery, while the noradrenaline concentration did not change significantly in heifers that needed assistance, but increased during expulsion in heifers calving without help. In the goats, adrenaline and noradrenaline concentrations increased in association with expulsion of the first kid. The beta-endorphin concentration increased during labour in goats. In heifers that needed assistance, beta-endorphin concentration increased 1 h after labour but there was no change in heifers that did not need assistance. The met-enkephalin concentration was elevated during expulsion in heifers and fluctuated in the goats. Both oxytocin and vasopressin increased during expulsion in both groups of heifers, but vasopressin increased four times more in heifers needing assistance. In the goats, oxytocin reached its highest levels just as the feet of the first kid became visible, and vasopressin peaked as the head emerged. Parturition took longer in heifers that needed assistance than in those that did not. It is concluded that, even though the pattern of change differed between hormones during labour, the changes were related to the phases of labour. A longer labour therefore meant that the hormone concentrations stayed elevated for longer. Vasopressin reached high levels in goats and was the only hormone for which plasma concentrations were higher in heifers that needed assistance than in those that did not, indicating that this hormone is released in order to deal with the pain-related stress associated with labour.

Analysis of Variance↗

Cardiovascular changes associated with dehydration and drinking in unrestrained, lactating goats.

The aim of this study was to investigate if the alertness connected with seeing water increased arterial blood pressure and heart rate to the same extent as the act of drinking, and if ingestion of warm water caused a different effect compared with ingestion of cool water on these cardiovascular variables. Seven goats of the Swedish domestic breed (Capra hircus) were used in a cross-over design. The animals were dehydrated for 24 h. They were allowed to watch water being prepared for 11-16 min, after which they were given access to warm (35 degrees C) or cool (15 degrees C) water. The goats drank 6.86 +/- 0.36 l of the warm water and 4.54 +/- 0.35 l of the cool water (P < 0.05) within the first hour. The arterial blood pressure, heart rate and activity of the animals were registered by an implanted telemetric device. Dehydration did not affect the cardiovascular variables, except before feeding in the morning, when the heart rate accelerated faster in dehydrated goats. Heart rate increased abruptly when dehydrated goats saw water being prepared, remained at the increased level during drinking and then slowly declined. It increased again during the afternoon feeding, to a level similar to that on control days, but between 18.00 and 06.00 h the heart rate was higher than during control nights. Blood pressure did not change when the goats saw water, but increased when they drank. On the morning following rehydration, the rise in heart rate in response to feeding was delayed compared with that during control and dehydration periods. It is concluded that seeing water caused arousal in the goats, resulting in an accelerated heart rate. The additional rise in blood pressure during the act of drinking appears to be a combination of excitement and sensory inputs from the pharyngeal region, causing a temporary activation of the sympathetic nervous system.

Animals↗

Lenticular opacities in individuals exposed to ionizing radiation in infancy.

Development of lens opacities and the measures taken to avoid them have clinical relevance in the fields of oncology, radiotherapy and radiation protection. The aim of this study was to correlate the prevalence of lenticular opacities in individuals exposed to ionizing radiation in childhood with radiation dose and other possible risk factors. Between 1920 and 1959, about 16,500 children (age <18 months) with skin hemangiomas were referred to Radiumhemmet, Karolinska University Hospital, 89% of whom were treated with radiotherapy. A total of 484 exposed individuals and 89 nonexposed controls participated in an ophthalmological examination. Lens opacities were found in 357 (37%) of the 953 lenses examined in the exposed persons. In contrast, lens opacities were observed in only 35 (20%) of the 178 lenses examined in the nonexposed control individuals. It is concluded that the increased prevalence of cortical and posterior subcapsular opacities is related to previous radiotherapy. Age at examination was the strongest modifier of risk. Children exposed to a lenticular dose of 1 Gy had a 50% increased risk (odds ratio 1.50; 95% confidence interval 1.10-2.05) of developing a posterior subcapsular opacity and a 35% increased risk of a cortical opacity (odds ratio 1.35; 95% confidence interval 1. 07- 1.69).

Adult↗

Improved quantitation of minimal residual disease in multiple myeloma using real-time polymerase chain reaction and plasmid-DNA complementarity determining region III standards.

The complementarity determining region III of the rearranged immunoglobulin heavy chain gene has been the target for tumor-specific PCR assays for the detection and follow-up of B-cell malignancies. Previously, these assays have relied on gel-based end point data collection methods (i.e., band densitometry) and, thus, have provided at best a semiquantitative assessment of tumor levels. We show the development of a novel, real-time TaqMan PCR assay to quantitate residual multiple myeloma cells in clinical samples after high-dose chemotherapy and autologous stem cell transplantation. We provide evidence that real-time PCR is reproducible, sensitive, and quantitative. In a 40-replicate PCR experiment targeting the beta-actin gene, the coefficient of variation for threshold cycle data was 1.6%, whereas it increased to 13.6% and 31%, respectively, for end point fluorescence and gel densitometry. Moreover, in an experiment directly comparing standard curves obtained from band densitometry and threshold cycle data, the standard curve constructed from threshold cycle data had a multiple R2 value of 1.00 and demonstrated a dynamic range >4 logs, compared with the 2-log linear range of gel densitometry. Finally, we show that when a complementarity determining region III-specific PCR primer is used in conjunction with a consensus primer for the immunoglobulin heavy chain joining gene, plasmid DNA can be used as a readily available and effective substitute for clonal plasma-cell genomic DNA when preparing standards. By applying real-time PCR to the analysis of clinical samples, we are able to quantitate levels of tumor involvement with unparalleled reproducibility and statistical confidence. Real-time PCR technology may well provide the accuracy and reliability necessary for minimal residual disease detection to have real prognostic significance.

Base Sequence↗

Psychophysiologic sensitization to headlight glare among professional drivers with and without cardiovascular disease.

Previous studies have shown that young, healthy professional drivers show heightened central nervous system arousal and cardiovascular hyperreactivity to simulated headlight glare. Electroencephalographic and cardiovascular response and recovery to simulated headlight glare (the glare pressor test) were examined in 4 groups of male professional drivers (age 25-52 years)--12 with ischemic heart disease (IHD), 12 with hypertension (HTN), 10 with borderline hypertension (BHTN), and 34 who were healthy--and in 23 non-professional driver controls--with the aim of assessing sensitization to this night driving stressor in relation to degree of cardiovascular disease severity. After glare exposure the IHD drivers showed the most pronounced alpha blockade, a rise in diastolic blood pressure (DBP; p < .05), and, unlike the other groups, a persistent fall in finger pulse volume (p < .02). The BHTN group reacted initially with DBP rise and finger pulse drop (ps < .05 and .02, respectively), mainly without central nervous system arousal. The DBP remained constant in normotensive professional drivers older than 40. The drivers' cardiovascular responses to glare were inversely related to reported stressors and subjective experience. Anxiety trait and long work hours were associated with heightened central arousal to glare in professional drivers. The results suggest that there may be progressive degrees of sensitization to glare exposure in these samples, with the least among normotensive professional drivers older than 40, moderate levels in borderline hypertensives, and the most severe in drivers with IHD.

Adaptation, Psychological↗

Diagnosis of pulmonary embolism by measurement of alveolar dead space.

OBJECTIVE: Pulmonary embolism (PE) gives rise to alveolar dead space, which can be measured with a single breath test for CO2 (SBT-CO2). The characteristics of the SBT-CO2 are different in PE and other common conditions giving rise to alveolar dead space, notably airways disease. An analysis of alveolar dead space focusing on the late part of the breath (fDlate) has been suggested as a method for diagnosis of PE. Our aim was to evaluate this technique by comparison with lung scintigraphy. METHODS: We randomly selected patients with clinical suspicion of PE. SBT-CO2 and lung scintigraphy were performed on the same day. The scintigraphies were reviewed and classified as high, intermediate and low probability of PE. RESULTS: Out of 223 patients able to be evaluated, there were 20 of the high, 29 of the intermediate and 174 of the low probability category. There were large differences between the means of fDlate in the high and the intermediate and in the high and the low categories. We obtained a sensitivity of 85% and a specificity of 93% for diagnosis of PE, based on high and low probability categories. If a patient with previous PE, but no scintigraphic evidence of current PE, is excluded the sensitivity increases to 90%. CONCLUSIONS: This study provides further support for the measurement of fDlate by the SBT-CO2 as a diagnostic test in patients with suspicion of PE. The test should be especially useful in small hospitals without access to pulmonary scintigraphy or pulmonary angiography.

Adult↗

Cortisol secretion and Alzheimer's disease progression.

BACKGROUND: Mild hypercortisolemia is a frequent concomitant of Alzheimer's disease (AD). In an effort to ascertain the relationship between serum cortisol concentration (CORT) and disease progression, aging, and survival, we followed 9 persons with AD, ages from 56 to 84 years, from an original cohort of 19 enrollees with serial cognitive testing and CORT determinations. METHODS: The cognitive instrument was a modification of the Alzheimer's Disease Assessment Scale-Cognitive (mADAS-COG). Serum cortisol determinations were performed at noon, and an Afternoon Cortisol Test (ACT) was used to obtain an estimate of average CORT. RESULTS: Baseline 12:00 hours CORT but not ACT correlated significantly with the change in mADAS-COG (r = .90, p < .01). ACT levels increased as the mADAS-COG increased over time (p = .037), by 0.156 +/- 0.06 microgram/dL for each one-point increase (indicating greater impairment) in cognitive test score. ACT levels did not increase significantly simply with aging. For the entire cohort of 19 subjects, neither baseline ACT nor 12:00 hours CORT was significantly related to survival. CONCLUSIONS: Hypercortisolemia in AD appears related to the clinical progression of the disease, but not to aging or length of survival.

Aged↗

The incidence and time-course of latanoprost-induced iridial pigmentation as a function of eye color.

Latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha administered as eye drops, induces increased melanogenesis in the iridial melanocytes of monkeys. Similar effects were seen in 12, 23 and 11% of patients in the USA, United Kingdom (UK) and Scandinavia, respectively, during one year of treatment. The highest incidence of induced pigmentation was seen in green-brown, yellow-brown and blue/grey-brown eyes, in that order. The relatively high proportion of patients with green-brown eyes in the UK explains the larger number of affected patients in this country. Typically, a concentric increase of the iris pigmentation appeared after six months (range: 3-17) and was judged to be noticeable by the patient in about 2/3 of the cases. After cessation of latanoprost, no change of the induced pigmentation has been seen in patients followed for two years, and there have been no signs of dispersion of pigment into the anterior chamber. Irides, homogeneously blue, grey, green or brown, were seldom affected. Naevi or freckles on iris, conjunctiva, or eye lids were not affected. It is intriguing that many patients with mixed eye color, particularly the blue-brown eyes, have not developed increased pigmentation even during two years of treatment. This could be due to a relatively slow melanogenesis or to refractory melanocytes in these individuals.

Adrenergic beta-Antagonists↗

The goat mammary gland as a target organ for atrial natriuretic peptide.

Milk secretion represents a major route for electrolyte and water excretion in the dairy goat. The aims of this study were to investigate whether the mammary gland is a target site for atrial natriuretic peptide (ANP) in the goat and whether ANP affects mammary sodium and water secretion. Receptor autoradiography using 125I-ANP as radioligand revealed specific binding sites in the secretory tissue of the mammary gland. The radioligand was totally displaced by unlabelled ANP, but not by brain natriuretic peptide or the ANP fragment c-ANP4-23, indicative of ANP-A receptor preference. To elucidate the role of ANP in milk secretion, ANP (30 ng kg-1 min-1; 120 min) or 0.15 M NaCl (control) were administered in vivo. The ANP infusions caused haemoconcentration, but did not change milk flow or the concentrations of sodium, potassium, lactose, fat and protein in the milk. The results show that the mammary gland of the goat expresses ANP-specific binding sites, however, a physiological role of ANP in goat mammary gland function remains to be elucidated.

Animals↗

Radiotelemetrically recorded blood pressure and heart rate changes in relation to plasma catecholamine levels during parturition in the conscious, unrestrained goat.

The aim of this study was to investigate the extent of sympathetic nervous system activation during parturition in four unrestrained goats. Chronically implanted radiotelemetry devices registered heart rate and arterial blood pressure around the clock and blood was sampled for determination of plasma adrenaline and noradrenaline concentrations before, during and after labour. Two goats delivered two kids after moderately intensive abdominal contractions. A third goat had dystocia, and was treated with prostaglandin F2 alpha. One normal kid and one mummified foetus were delivered manually. After milking, a third kid was born spontaneously. The fourth goat experienced severe abdominal contractions and delivered one kid. Mean blood pressure was 69 +/- 2 mmHg the day before parturition, increased gradually during the labour pains, and reached a maximal value of 120 +/- 7 mmHg when the head of the first kid was visible (P < or = 0.05). Heart rate was 134 +/- 4 beats min-1 the day before parturition and peaked when the first kid was born (159 +/- 6 beats min-1, P < or = 0.05), as did plasma adrenaline concentration (from 0.4 +/- 0.2 nmol L-1 to 2.7 +/- 1.2 nmol L-1, P < or = 0.05). The concentration of noradrenaline increased from 4.8 +/- 2.3 nmol L-1 to 12.2 +/- 8.4 nmol L-1 (P < or = 0.05), when the head of the first kid was visible. Expulsion of the second and third kids caused relatively smaller increases in blood pressure, heart rate and catecholamines than those seen with the first born kid. It is concluded that changes in pressure, heart rate and catecholamines during parturition are related to the different phases of labour and not to its duration or severity.

Animals↗

Parathyroid hormone-related protein in neonatal and reproductive goats determined by a sensitive time-resolved immunofluorometric assay.

OBJECTIVE: High concentrations of parathyroid hormone-related protein (PTHrP) have been found in goat milk but it is not known whether it can enter the circulation of the neonate. In this study we have developed a sensitive two-site lanthanide immunofluorometric assay (IFMA) using dissociation and enhancement time-resolved fluorometry to address this question. METHOD: Affinity-purified anti-PTHrP 38-67 raised in rabbit was biotinylated and immobilized in streptavidin-coated microtitration wells as a 'capture' antibody. As a signal, affinity-purified anti-PTHrP 1-34, raised in sheep, was labeled with an europium chelate. A sensitivity of 0.3 pmol/l was achieved. PTHrP levels were determined in the plasma of eleven neonatal, seven parturient and six non-pregnant, non-lactating goats as well as in goat milk. RESULTS: The circulating PTHrP levels (mean +/- S.D.) were significantly increased at day 1 (6.1 +/- 1.7 pmol/l: P < 0.01) and day 3 (3.5 +/- 0.6 pmol/l: P < 0.05) after birth in the male kids (n = 8) bottle-fed with milk from the dams, compared with before (2.2 +/- 0.7 pmol/l) and 30 min after (2.0 +/- 0.6 pmol/l) the first feeding and 14 days (2.4 +/- 0.8 pmol/l) later. In the female kids (n = 3) fed with formula there was no such increase and the concentrations remained between 1.6-1.9 pmol/l. In the parturient goats the mean +/- S.D. PTHrP levels before, during and after parturition were 2.9 +/- 1.7, 4.2 +/- 2.4 and 3.7 +/- 2.2 pmol/l respectively (n = 7) which demonstrated that plasma PTHrP was higher during and after parturition in comparison with before (P < 0.05). The levels in non-pregnant, non-lactating goats were 3.3 +/- 1.5 pmol/l (n = 6). PTHrP levels in goat milk were in the nanomolar range and were highest in the colostrum. CONCLUSIONS: A significant increase of plasma PTHrP was observed in goat kids fed with milk from their dams and this increase was not found in kids fed with formula. Plasma PTHrP was also increased during parturition.

Aging↗

Effects of naturally acquired decompensated mitral valve regurgitation on the renin-angiotensin-aldosterone system and atrial natriuretic peptide concentration in dogs.

OBJECTIVE: To investigate activity of the renin-angiotensin-aldosterone system and N-terminal pro-atrial natriuretic peptide (NT-proANP) during development of clinical signs of decompensated mitral valve regurgitation (MR). ANIMALS: 11 Cavalier King Charles Spaniels with advanced MR attributable to chronic valvular disease. PROCEDURE: Dogs were subjected to repeated examinations at 6-month intervals until signs of decompensation had developed (end point). Data acquired at end point were compared with data obtained from examinations 1 year and 1 to 6 months before decompensation. Each examination included physical examination, collection of venous blood, thoracic radiography, and echocardiography. RESULTS: Echocardiographic measurements of left atrial-to-aortic root ratio and left ventricular end diastolic diameter increased considerably during the study, whereas left ventricular end systolic diameter remained unchanged. The increase in cardiac size was associated with increased plasma concentration of NT-proANP. In contrast, plasma concentrations of aldosterone and angiotensin II were reduced at decompensation (aldosterone compared with the 2 earlier examinations and angiotensin II compared with values obtained 1 to 6 months before), despite decreased plasma protein concentration and hematocrit, suggesting fluid retention. The urine-to-plasma creatinine ratio was reduced at end point. CONCLUSION AND CLINICAL IMPLICATIONS: Early decompensated MR in dogs was not associated with increased circulating renin-angiotensin-aldosterone system activity, which may be caused by increased activity of ANP, and may be important for future therapeutic strategies of MR.

Aldosterone↗