[A new diagnostic method: somatostatin receptor scintigraphy of neuroendocrine tumors].
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Carcinoid Tumor↗
Biomedical subjects
S Nilsson
Publications and source records attributed to S Nilsson.
Evidence for a non-estrogenic cytostatic effect of estramustine on human prostatic carcinoma cells in vivo.
Estramustine is one of the main metabolites of estramustine phosphate (EstracytR), a drug used in the treatment of advanced prostatic cancer. In the present study the hormone independent human prostatic carcinoma cell line DU 145 implanted subcutaneously in nude mice (NMRI) was used to investigate the mode of action of estramustine in vivo. Metaphase arrest was found in mice treated with estramustine intraperitoneally, 200 and 400 micrograms daily for 2 weeks, 5 days a week. A significant dose dependent decrease in the number of anaphase figures was found. A 7 to 8 fold increase in the number of abnormal metaphases, i.e., highly contracted and unaligned chromosomes, was found. Uptake and retention of 3H-estramustine was found in tumour tissue. No increase in the mitotic index or the number of abnormal metaphases was found in animals treated with polyestradiol phosphate (EstradurinR). This is the first time evidence has been presented demonstrating the anti-mitotic effect of estramustine in vivo.
Animals↗
Radiation sensitization by estramustine studies on cultured human prostatic cancer cells.
In low-stage prostatic carcinoma, local cure can be obtained with radiation therapy alone, while in locally advanced disease the chances for cure are less. In this study, we have addressed the question of whether estramustine (EM), the main cytostatic metabolite of estramustine phosphate (Estracyt), may act as a radiosensitizing agent. This drug accumulates in prostatic cancer and has also been shown to arrest cancer cells at metaphase both in vitro and in vivo. The human prostatic cancer cell line DU 145 was grown as cultures monolayer and incubated with EM in concentrations varying from 1 to 20 micrograms/ml. External beam irradiation was performed with doses ranging from 0 to 8 Gy using gamma rays from a 60Co source. Clonogenic cell survival (CS) was used to analyse the radiation sensitizing effect of EM. The radiation dose modifying factor (DMF) at the survival level 0.1 was found to be 0.77 in the presence of EM (5 micrograms/ml), i.e., 23% sensitization was obtained. When irradiating cells at the standard fraction dose of 2 Gy in the absence of EM, 22% of the cells lost their clonogenic ability. In presence of EM (5 micrograms/ml), 2 Gy caused 40% of the cells to lose their clonogenic ability. Thus a radiation sensitizing effect of EM was established in the CS assay. It was also of interest to determine if the radiosensitizing effect of EM could be confirmed in a rapid assay. The rapid fluorescence assay was used to observe early damage of the cells. Results showed that by 2 days after exposure to irradiation a weak tendency towards sensitization was seen, while a clear sensitization was obtained after 4 days. This indicates that the rapid assay might be developed to a predictive assay for detection of the response of primary prostate tumor cells to the radiation sensitizing effect of EM.
Cell Survival↗
Ultrasonic dating of pregnancies: effect on incidence of SGA diagnoses. A randomised controlled trial.
In order to study the incidence of antenatal identification and postnatal diagnosis of small for gestational age (SGA) infants, 4997 women with optimal menstrual history were randomised. One group had the gestational age estimated from last menstrual period (LMP), the other from ultrasonographically measured biparietal diameter (BPD) in the second trimester. Both the incidence of antenatally suspected and postnatally diagnosed SGA infants were reduced by approximately 30% in the BPD-dated group. It is concluded that this was due to the shift in gestational age estimation.
Female↗
Effects on lipids and lipoproteins in women treated with oestradiol and progesterone.
Thirty women with climacteric symptoms were treated for 4 months with 2 mg 17 beta-oestradiol and different doses of progesterone (50, 100 or 200 mg). The concentrations of total and free cholesterol, phospholipids, triglycerides (TG), apoprotein A1 and apoprotein B were determined in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) fractions and in serum. HDL levels increased and LDL levels decreased, while TG levels in VLDL remained unchanged, which indicates that the lipoprotein pattern is oestrogen-induced and that progesterone exerts little or no influence.
Adult↗
Latex-based thin-layer immunoaffinity chromatography for quantitation of protein analytes.
A rapid immunochromatographic method for qualitative and quantitative analysis of protein antigens is described. The method is based on the "sandwich" assay format using monoclonal antibodies (Mabs) of two distinct specificities. Mabs of one specificity are covalently immobilized to a defined detection zone on a porous membrane while Mabs of the other specificity are covalently coupled to blue latex particles which serve as a label. The sample is mixed with the Mab-coated particles and allowed to react. The mixture is then passed along a porous membrane by capillary action past the Mabs in the detection zone, which will bind the particles which have antigen bound to their surface, giving a blue color within this detection zone with an intensity logarithmetrically proportional to the antigen concentration in the sample. Analysis is complete in less than 10 min, requires a minimum amount of sample (4 microliters), and has a detection limit below the nanomolar range for the antigen we studied, human chorionic gonadotropin.
Antibody Specificity↗
The expression of estramustine-binding protein in the human prostatic cancer cell line DU 145 is not androgen dependent.
Estramustine-binding protein (EMBP) constitutes one of the major proteins in the prostatic gland, it binds estramustine and estromustine, the active metabolites of estramustine phosphate (Estracyt). Previous studies in rats have indicated that the expression of EMBP is androgen dependent, with diminishing quantities following castration and estrogen treatment as well as restored pre-castration production upon administration of androgens. In this study, we have used the human prostatic cancer cell line DU 145 transplanted in female and male nude mice. This cell line, which is sex hormone independent, gave rise to subcutaneous tumors in the rats with no difference in growth characteristics between the males and females. The expression of EMBP was analysed by radioimmunoassay, immunohistochemical and Western blot techniques. No difference was seen between the two sexes with respect to EMBP content, demonstrating that the expression of EMBP, in contrast to that reported for the normal prostate, is neither androgen- nor estrogen-dependent in tumor tissues.
Animals↗
Correlation between computer-assisted femoral arteriography and physiological tests in hypercholesterolaemic patients: a methodological study with special reference to clinical trials.
The validity of computer-assisted femoral arteriography, for the study of regression/progression of atherosclerosis in follow-up clinical trials, was investigated by comparison with routine physiological estimates of peripheral circulatory function. Thus, in 114 hypercholesterolaemic patients, the results of aorto-femoral arteriography were compared with those of leg segmental blood pressure measurement, oscillometry, digital pulse plethysmography, and bicycle and treadmill exercise tests. In 107 patients, 18 with symptoms of peripheral vascular disease (PVD) and 89 asymptomatic, magnification arteriograms of a 20 cm segment of the right or left superficial femoral artery were obtained. These arteriograms were digitized and the following variables were calculated: arterial lumen volume (corrected for body size), per cent stenosis, and edge roughness. The correlation between arteriographic and physiological variables was investigated with a linear regression model, taking into account the possible interaction with sex, and presence or absence of symptoms of PVD. Lumen volume correlated significantly with all five physiological variables, and per cent stenosis correlated significantly with four of the physiological variables. For the roughness measure, however a significant correlation was found only with plethysmography. By using logistic multiple regression analysis linear functions of physiological variables were constructed to detect ilio-femoral arterial occlusion. The sensitivity/specificity for detection of right-sided, left-sided, and bilateral occlusion was 0.83/0.98, 0.78/0.98, and 0.60/1.00 respectively (N = 108-111). Systolic blood pressure (ankle-arm ratio) was the single variable most closely correlated to the likelihood of arterial occlusions. It is concluded that arterial lumen volume and per cent stenosis, measured for the digitized femoral arteriogram, correlate well with physiological variables, which reflect the state of atherosclerosis both in the femoral arteries and in other arterial beds including the heart, and that routine physiological tests can be used to identify patients with arterial occlusions in the iliac and femoral arteries.
Adult↗
Expression of birch pollen-specific IgE-binding activity in seeds and other plant parts of birch trees (Betula verrucosa Ehrh.).
Dot immunoblotting of crude extracts of various aerial parts of birch trees, using patient serum rich in birch pollen IgE, showed IgE-binding activity in leaves, buds, twigs, seeds, bark, and old male catkins. Seed extracts analysed by SDS-PAGE, electroblotting to nitrocellulose and immune detection using isotope-conjugated anti-IgE verified the presence in seeds of an IgE-binding protein of an approximate molecular weight of 12 kD, distinct from the major allergen (molecular weight 17 kD) of Betula verrucosa pollen. The allergen of birch seeds was readily leachable from the seeds. Many of the birch plant part extracts were active in RAST inhibition using birch pollen RAST discs, but showed low potency relative to the allergenicity of birch pollen allergens.
Allergens↗
Acupuncture for tinnitus management.
Fifty-six patients with continuous and severe tinnitus as their major complaint were treated with traditional Chinese acupuncture. After a pre-treatment period with baseline evaluation of tinnitus, 10 treatments were given during a period of 20 days, followed by a post-treatment period in order to obtain indications of prolonged treatment effects. Assessments were made using visual analogue scales (VAS) and a verbal retrospective rating scale. Three patients reported improvement which lasted for at least 10 days after the last treatment, indicating a possible long-term effect in some cases. Twenty-one percent of the patients reported transient intensity reductions lasting for hours/days. Estimated 'substantial' improvement rate by VAS, consistent for all three parameters involved (intensity, annoyance, awareness), was 20%, while the corresponding deterioration rate was 25%. Statistical analysis of the whole group did not show any significant general treatment effects. Interactions between treatment evaluations by verbal rating and VAS are discussed as well as interactions with psychological components.
Acupuncture Points↗
Computer-assisted femoral arteriography in serial assessment of atherosclerosis. A methodologic study.
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Adult↗
Cloning, sequence, and developmental expression of a type 5, tartrate-resistant, acid phosphatase of rat bone.
Tartrate-resistant acid phosphatase (TRAP) is a characteristic constituent of osteoclasts and some mononuclear preosteoclasts and, therefore, used as a histochemical and biochemical marker for osteoclasts and bone resorption. We now report the isolation of a 1397-base pair (bp) full-length TRAP/tartrate-resistant acid ATPase (TrATPase) cDNA clone from a neonatal rat calvaria lambda gt11 cDNA library. The cDNA clone consists of a 92-bp untranslated 5'-flank, an open reading frame of 981 bp and a 324-bp untranslated 3'-poly(A)-containing region. The deduced protein sequence of 327 amino acids contains a putative cleavable signal sequence of 21 amino acids. The mature polypeptide of 306 amino acids has a calculated Mr of 34,350 Da and a pI of 9.18, and it contains two potential N-glycosylation sites and the lysosomal targeting sequence DKRFQ. At the protein level, the sequence displays 89-94% homology to TRAP enzymes from human placenta, beef spleen, and uteroferrin and identity to the N terminus of purified rat bone TRAP/TrATPase. An N-terminal amino acid segment is strikingly homologous to the corresponding region in lysosomal and prostatic acid phosphatases. The cDNA recognized a 1.5-kilobase mRNA in long bones and calvaria, and in vitro translation using, as template, mRNA transcribed from the full-length insert yielded an immunoprecipitated product of 34 kDa. In neonatal rats, TRAP/TrATPase mRNA was highly expressed in skeletal tissues, with much lower (less than 10%) levels detected in spleen, thymus, liver, skin, brain, kidney, brain, lung, and heart. In situ hybridization demonstrated specific labeling of osteoclasts at endostal surfaces and bone trabeculae of long bones. Thus, despite the apparent similarity of this osteoclastic TRAP/TrATPase with type 5, tartrate-resistant and purple, acid phosphatases expressed in other mammalian tissues, this gene appears to be preferentially expressed at skeletal sites.
Acid Phosphatase↗
Galanin inhibits the potassium-evoked release of acetylcholine and the muscarinic receptor-mediated stimulation of phosphoinositide turnover in slices of monkey hippocampus.
In the ventral hippocampus of Cynomologus monkey, galanin, a 29 amino acid long neuropeptide, reduced the potassium-evoked release of [3H]acetylcholine from slices preloaded with [3H]choline and diminished the carbachol-stimulated accumulation of [3H]inositol polyphosphates in hippocampal microprisms preincubated with myo-[2-3H]inositol. Using receptor autoradiography a strong, specific binding of iodinated galanin was observed in the molecular layer of the dentate gyrus. These may thus be the sites where galanin exerts its inhibitory effects on acetylcholine (ACh) release and phosphoinositide breakdown. These data provide evidence that galanin is a modulator of cholinergic function in septo-hippocampal neurons of primates.
Acetylcholine↗
M-15: high-affinity chimeric peptide that blocks the neuronal actions of galanin in the hippocampus, locus coeruleus, and spinal cord.
The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.
Acetylcholine↗
Synthesis of the trisaccharide, 2-(p-trifluoroacetamidophenyl)ethyl O-alpha-D-galactopyranosyl-(1-4)-O-beta-D-galactopyranosyl-(1-4)-2-acet amido-2-deoxy-beta-D-glucopyranoside, corresponding to the blood group P1 determinant.
The 2-(p-trifluoroacetamidophenyl)ethyl beta-glycoside of the P1 antigen trisaccharide, O-alpha-D-galactopyranosyl-(1-4)-O-beta-D-galactopyranosyl-(1-4)-2- acetamido-2-deoxy-D-glucopyranose, was synthesized. Thioglycoside intermediates were used as building blocks.
Carbohydrate Sequence↗
Premenstrual tension: a placebo-controlled efficacy study with spironolactone and medroxyprogesterone acetate.
Forty-three healthy women with a characteristic history of premenstrual tension participated in a placebo controlled, crossover study. The effects of spironolactone (Aldactone) and medroxyprogesterone acetate (Gestapuran) on ten symptoms of premenstrual tension were evaluated. Placebo tablets as well as spironolactone and medroxyprogesterone acetate significantly improved a mood index score (which is a generally accepted method to measure premenstrual symptoms). Spironolactone and medroxyprogesterone acetate were however both significantly (P less than 0.05) better than placebo in relieving the symptoms.
Adult↗
Image operations in quantification of atherosclerosis from digitized angiograms.
This report describes a method of quantifying the inner volume (lumen volume) of a contrast medium-filled femoral artery from a roentgenogram by computerized image analysis. The various factors influencing the accuracy of the volume determination are analyzed and an image-processing procedure for the elimination of artifacts due to crossing arteries is described and evaluated. The presented methods have been used in a large study of 281 patients and the short-term reproducibility has been found to be 1.00.
Arteriosclerosis↗
Gut blood flow in the estuarine crocodile, Crocodylus porosus.
Simultaneous recordings of blood flow in the right and left aorta and carotid and coeliac artery were made in the crocodile, Crocodylus porosus at rest and during various stimuli. In resting animals the right aorta and carotid artery flow profiles resembled the recordings obtained in the caiman (Axelsson et al. 1989a), with an anterograde blood flow throughout the cardiac cycle. As in the caiman, the left aorta flow profile was complex with both anterograde and retrograde blood flow during the cardiac cycle, and a net left aorta blood flow near zero at rest. The coeliac artery blood flow profile did not show the complex pattern seen in the upper aorta, immediately suggesting that most of the coeliac artery blood originates elsewhere. We believe that coeliac artery blood flow in the resting animal derives from the right aorta via the abdominal anastomosis between the two aortas. Feeding induced an increase in the coeliac artery and left aorta blood flow, probably due to a decrease in visceral vascular resistance, and hence coeliac arterial and the left aorta blood pressure, which facilitates blood flow (from right to left aorta) through the foramen of Panizza. During short 'fright dives', heart rate fell and there was a decrease in the recorded blood flows: carotid artery blood flow did not decrease to the same extent as the RAo and coeliac artery flow, indicating some capacity for redistribution of blood to the cephalic circuits during diving. Similarly, a near-unimpaired carotid artery blood flow was maintained after adrenaline injection. Substance P increased the coeliac artery blood flow and produced a right-to-left cardiac shunt, probably by construction of the pulmonary vasculature.
Alligators and Crocodiles↗