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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 271 records · Page 15Linked to original sources

Treatment of growth hormone-deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters.

In a double-blind, placebo-controlled trial, the effects of recombinant human growth hormone were studied on cerebrospinal fluid concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), monoamine metabolites, neuropeptides and endogenous opioid peptides. Twenty patients, 10 patients in each of 2 groups, with adult-onset, growth hormone deficiency were treated for 1 month with recombinant human growth hormone (0.25 U/kg/week) or placebo. All the patients received the appropriate thyroid, adrenal and gonadal hormone replacement. In cerebrospinal fluid, the mean concentration of growth hormone increased from 13.3 +/- 4.4 to 149.3 +/- 22.2 muU/l (p = 0.002), during recombinant human growth hormone treatment. The cerebrospinal fluid IGF-I concentration increased from 0.67 +/- 0.04 to 0.99 +/- 0.10 micrograms/l (p = 0.005) and the IGFBP-3 concentration rose from 13.4 +/- 1.25 to 17.5 +/- 1.83 micrograms/l (p = 0.002). The dopamine metabolite homovanillic acid decreased from 282.1 +/- 36.0 to 234.3 +/- 26.5 nmol/l (p = 0.02) and the vasoactive intestinal peptide decreased from 4.1 +/- 0.6 to 3.7 +/- 0.4 pmol/l (p = 0.03). Cerebrospinal fluid immunoreactive beta-endorphin increased from 24.4 +/- 1.8 to 29.9 +/- 2.1 pmol/l (p = 0.002). There were no significant changes compared to baseline in the cerebrospinal fluid concentrations of enkephalins, dynorphin A, the norepinephrine metabolite 3-methoxy-4-hydroxyphenyl-ethyleneglycol, the serotonin metabolite 5-hydroxyindoleacetic acid, gamma-aminobutyric acid, somatostatin or corticotropin-releasing factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Various methods for testing nasal responses in vivo: a critical review.

Mucosal responses in the airway can ideally be studied in the nose. It is a readily accessible organ and can be provoked repeatedly. Likewise, mucosal responses to certain provocations can be easily monitored. Different methods for the provocation and measurement of nasal responses have been used in recent years. Each technique has its own advantage and restrictions. In order to make a correct interpretation of the results achieved, however, it is important that the investigator is familiar and comfortable with the methods used. For clinical purposes, techniques for qualitative measurements may be appropriate, but for experimental research, quantitative measurements with high reproducibility are essential. The present paper critically discusses current techniques for provocation and assessment of nasal responses, which may improve both the techniques used and the understanding of nasal physiology.

Alkaloids↗

Involvement of loop 2 of platelet-derived growth factor-AA and -BB in receptor binding.

Platelet-derived growth factor (PDGF) is a disulfide-bonded antiparallel dimer of A- and B-polypeptide chains. Each subunit contains two loops (loops 1 and 3) which point in the same direction, and which are located close to a region (loop 2) from the other subunit of the dimer. Previous studies have shown that epitopes in loops 1 and 3 are important for binding to PDGF alpha- and beta-receptors. The aim of the present investigation was to determine the importance of loop 2 for receptor interactions. PDGF A- and B-chain cDNA:s were mutated in the loop 2 regions and transfected into COS cells. Analyses of conditioned media of such cell cultures revealed that PDGF B-chain mutated in the loop 2 region lost its ability to compete with 125I-PDGF for binding to PDGF beta-receptors, but retained 2-5% of its binding of alpha-receptors. The A-chain binds only to alpha-receptors; 2-5% of this binding was also retained after mutation of the loop 2 region. In conclusion, the loop 2 region of PDGF is important for receptor binding, but appears to be more important for binding to the PDGF beta-receptors than to the alpha-receptors.

Amino Acid Sequence↗

Mortality and cancer incidence after cerebral arteriography with or without Thorotrast.

Mortality and cancer incidence among 999 neurological patients exposed to chronic alpha-particle irradiation from 232ThO2 (Thorotrast) administered for cerebral angiography in 1935-1947 was compared to that of 1480 similar patients examined with cerebral angiography without Thorotrast in 1946-1963 (controls). The ratio of standardized mortality/morbidity ratios (SMRs) for patients exposed to Thorotrast and controls was the relative risk, which was analyzed by multiplicative regression (RRREG). For mortality from all causes, RRREG was significantly increased mainly due to cancer, benign and unspecified tumors and benign liver conditions, while RRREG for all other causes combined was not significantly increased. The RRREG was significantly associated with the injected amount of Thorotrast for cancer and for benign liver conditions, while no other dependence on the amount of Thorotrast was seen. Cancer incidence was significantly increased, caused mostly by liver cancer, leukemia, metastases and cancer at unspecified sites. The risk for cancer other than liver, hematological, brain, metastases and cancer at unspecified sites combined was also significantly increased, but the temporal trend of RR for this category of sites did not indicate a radiation effect. A significant association between relative risk of cancer and injected amount of Thorotrast was largely accounted for by liver cancer. Thus increased mortality among patients exposed to Thorotrast is due mainly to cancer and benign liver diseases, and increased cancer incidence is caused by high risks of liver cancer, leukemia and ill-defined types (metastases, etc.). The time trend and dependence of the amount of Thorotrast injected do not support that cancer at most other sites is related to radiation from Thorotrast.

Adolescent↗

A comparison of budesonide nasal dry powder with fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis.

There is circumstantial evidence that the incidence of allergic rhinitis is becoming increasingly common. There may also be a need for more potent drugs with minimal local and systemic side effects. This study has compared the efficacy and safety of budesonide delivered as nasal dry powder with fluticasone propionate aqueous nasal spray in the treatment of perennial allergic rhinitis. Ninety-eight patients participated in a randomized, parallel group and partly blinded study. Treatment consisted of budesonide dry powder (Rhinocort Turbuhaler) at once daily doses of 200 micrograms (n = 24) or 400 micrograms (n = 22), fluticasone propionate (200 micrograms) once daily (n = 25), and placebo for budesonide dry powder (n = 27). A six-week treatment period was preceded by a two-week baseline period without treatment. Efficacy was assessed by daily subjective scoring of nasal symptoms. Safety was assessed by rhinoscopy, analysis of urine cortisol, and questioning of adverse events. All active treatments were significantly superior to placebo in controlling nasal symptoms. No significant differences in efficacy were found between the two budesonide regimens and fluticasone propionate. Adverse events were few and minor, and non-significantly distributed between treatments. In conclusion, this study shows that budesonide dry powder administered from Turbuhaler (200 or 400 micrograms) and fluticasone propionate aqueous spray (200 micrograms) administered in once daily doses, are effective and safe treatments of perennial allergic rhinitis. These novel treatments may enhance the current available alternatives in clinical practice.

Administration, Topical↗

A new computer-assisted method for fabrication of crowns and fixed partial dentures.

The availability of high-technology systems that use computer-aided design and computer-aided machining is on the increase. One such system is the Procera system, which is currently providing cost-effective, high-quality dental restorative services to dental laboratories and to dentists. A reduction in cost to the dentist, and ultimately to the patient, is a major advantage of the Procera system. Cost benefits combined with its continued success in producing crowns and fixed partial dentures that meet professional standards of care should enhance the acceptance of this new technology.

Computer-Aided Design↗

Effects of preconceptional irradiation on mortality and cancer incidence in the offspring of patients given injections of Thorotrast.

BACKGROUND: Findings from a British case-control study suggest that a preconceptional paternal external radiation dose of more than 100 mSv (10 rem) is significantly related to risk for leukemia and non-Hodgkin's lymphoma in offspring. The suggestion, however, has not been supported by experimental or other epidemiologic studies. PURPOSE: The purpose of this study was to investigate if preconceptional irradiation of males and females from internally deposited radionuclides affects mortality and risk of developing cancer in their offspring. METHODS: The offspring of 260 females (n = 143) and 320 males (n = 226) who lived longer than 1 year after receiving Thorotrast (a compound no longer in use) for cerebral arteriography were studied for mortality rate and the risk for developing cancer. Thorotrast was used as a contrast medium containing a 20% colloidal solution of thorium dioxide-Th 232, an alpha particle-emitting radionuclide, which is retained lifelong in nearly all organs. The offspring of the exposed patients were identified by manual linkage with the municipal population registers and followed-up for vital status by computerized linkage with the Danish National Central Population Registry and for incidence of cancer by computerized linkage with the Danish National Cancer Registry. The standardized mortality/morbidity ratios (SMRs) for death and for site-specific incidence of cancer in the offspring were calculated as ratios of the observed rates in the study population to the expected rates in the general population. RESULTS: After a median follow-up of 40 years, four cases of cancer (breast [one], uterine cervix [one], melanoma of skin [one], and retinoblastoma [one]) versus 2.9 cases expected, developed among 143 children born to mothers who received injections of Thorotrast (SMR = 1.4; 95% confidence interval [CI] = 0.4-3.5), while six cases of cancer (one case each of cancer of lung, testis, thyroid, and Hodgkin's lymphoma and two cases of melanoma of skin), versus 4.5 expected, occurred among 226 children of exposed fathers (SMR = 1.3; 95% CI = 0.5-2.9). No case of leukemia or non-Hodgkin's lymphoma occurred in any of the offspring studied. Mortality was lower than expected both for children of exposed mothers (SMR = 0.7; 95% CI = 0.3-1.5) and of exposed fathers (SMR = 0.5; 95% CI = 0.2-1.0). CONCLUSIONS: This study does not support the previously proposed association between parental exposure to radiation and the risk of childhood leukemia and lymphoma. Furthermore, since mortality from all causes was not increased in any offspring, our results do not support the belief that preconceptional parental low-dose exposure to alpha radiation increases the incidence of cancer or mortality in the offspring.

Adolescent↗

Modulations in hepatic branch-point enzymes involved in isoprenoid biosynthesis upon dietary and drug treatments of rats.

Three branch-point enzymes of the mevalonate pathway, farnesyl pyrophosphate synthase, cis-prenyltransferase and squalene synthase were characterized in rat hepatic cytosol, microsomes and peroxisomes isolated from rats after treatment with peroxisome proliferators, inducers of the endoplasmic reticulum or modulators of lipid metabolism. Cholestyramine and phenobarbital induced primarily the cytosolic farnesyl pyrophosphate synthase, whereas clofibrate and phthalates elevated the corresponding peroxisomal activity. cis-Prenyltransferase activities in microsomes were induced 4-5-fold after clofibrate, phthalate and phenobarbital administration, but these same treatments affected the peroxisomal activity to only a limited extent. Squalene synthase activity in microsomes was completely abolished, but the peroxisomal activity was unaffected after administration of cholesterol. On the other hand, clofibrate and phthalate induced only the microsomal activities. Mevinolin treatment greatly increased peroxisomal and cytosolic farnesyl pyrophosphate synthase activities, but not the mitochondrial activity, and the cis-prenyltransferase activities were elevated in peroxisomes, but not in microsomes. These results demonstrate that the branch-point enzymes in cholesterol and dolichol biosynthesis at various cellular locations are regulated differentially and that the capacities of peroxisomes and the endoplasmic reticulum to participate in the synthesis of polyisoprenoid lipids is affected profoundly by treatment with different xenobiotics.

Animals↗

A method for protein assay in Laemmli buffer.

A simple, cheap, and rapid assay for soluble and membrane-bound protein solubilized in Laemmli sodium dodecyl sulfate sample buffer is described. Following the addition of trichloroacetic acid to a final concentration of 24%, the induced turbidity was measured at 570 nm in a microplate reader, after an incubation period of approximately 10-30 min. The assay is suitable for measuring bovine serum albumin at a concentration of 15 to 500 micrograms/ml in Laemmli buffer, corresponding to 2 to 75 micrograms protein per well on the microtiter plate. Other nonproteinaceous macromolecules in the sample may introduce an error.

Animals↗

Characterization of the retention motif in the C-terminal part of the long splice form of platelet-derived growth factor A-chain.

Platelet-derived growth factor (PDGF) A-chain is found in two different splice variants; the long A-chain variant differs from the short one in that it contains a stretch of basic amino acid residues in the C-terminal part that mediates retention of the growth factor inside the producer cell and to the cell matrix. By analyzing mutants in which different amino acid residues in the retention motif had been changed to alanine residues, we found that the total positive charge of the sequence is of importance for the function of the retention motif. Moreover, we showed that retention also occurs if only one of the polypeptides in the PDGF dimer carries the retention motif. Surface iodination and competition with a peptide having the sequence of the retention motif revealed that the long A-chain variant, in contrast to the short A-chain variant, is localized on the outside of the cells and is also associated to the cell matrix. The association is likely to be mediated partially through heparan sulfate proteoglycans since treatment of matrix with heparitinase released the long A-chain variant.

Alternative Splicing↗

Calpains in lens epithelium from patients with cataract.

Lens epithelium from patients with cataract was obtained during surgery and frozen. The samples were subjected to SDS-electrophoresis and Western blotting. Calpains were quantified using polyclonal antibodies against m- and mu-Calpain could be detected but not the isoenzyme mu-calpain, indicating that m-calpain is the significant most important calpain in human lens epithelium. Quantification of m-calpain showed no relationship to age or gender, but there were significant differences between different types of cataract.

Adult↗

In vivo dynamical distribution of 131I-VIP in the rat studied by gamma-camera.

The in vivo distribution of vasoactive intestinal peptide (VIP) was studied for the first time using a rat model in combination with labeled VIP (131I-VIP) and a gamma-camera. A dynamic scan showed that 131I-VIP was cleared rapidly from the blood circulation. The radioactivity was taken up and accumulated in the lungs during the first minute. During the next 15 min, the radioactivity was slowly removed from the lungs and redistributed into the kidneys, gastric mucosa, liver and small intestine. However, the radioactivity extracted by the lungs was about 6-fold lower during the first minute when a large amount of the non iodinated VIP was coinjected with the 131I-VIP. 131I-VIP was eliminated rapidly from the blood with a half-life of 0.44 +/- 0.05 (min +/- SD) while in lung the elimination half-life was determined to 2.3 +/- 0.8 (min +/- SD). Of the radioactivity in the lungs, 2% was found to be intact 131I-VIP after 20 min. In all other organs the radioactivity found was assumed to be low molecular weight fragments of 131I-VIP. We suggest that lungs play an important role to extract VIP from the circulation after an i.v. administration. 131I-VIP degradation products are redistributed mostly to the kidneys and to the gastric mucosa to be excreted through urine and stomach contents, respectively.

Animals↗

Hepatic accumulation of alpha-1-antitrypsin in chronic liver disease in the dog.

Alpha-1-antitrypsin deficiency has long been known to cause liver cirrhosis in man, but whether it does so in the dog is uncertain. To investigate this point 57 dogs with clinically and histopathologically diagnosed chronic liver disease were examined. Isoelectric focusing of blood serum from these dogs and from 25 clinically healthy dogs revealed three different types of alpha-1 antitrypsin, designated F(fast), I(intermediate) and S(slow). They appeared in both homozygous and heterozygous forms, the F type being seen most frequently. The I type was more common in cocker spaniels than in other breeds. Immunostaining for alpha-1 antitrypsin revealed that 37 diseased dogs had alpha-1 antitrypsin in the cytoplasm of their hepatocytes. Of these, 21 dogs had globular alpha-1 antitrypsin inclusions in the endoplasmic reticulum, indicating aggregated protein. Accumulated alpha-1 antitrypsin was found most frequently in dogs having the I and S types of alpha-1 antitrypsin, either homozygously or heterozygously. With a few exceptions, F-homozygotic dogs had no hepatocellular alpha-1 antitrypsin accumulation. As alpha-1 antitrypsin aggregation is lethal to hepatocytes and as cell death attracts mononuclear blood cells whose cytokines induce continued alpha-1 antitrypsin synthesis with subsequent risk of further alpha-1 antitrypsin accumulation, liver disease may thus be maintained. Whether alpha-1 antitrypsin aggregates actually initiate liver disease in dogs, as in man, remains to be elucidated by further biochemical investigation of the three canine alpha-1 antitrypsin types found.

Animals↗

Human nasal absorption of 51Cr-EDTA in smokers and control subjects.

Passive exposure to cigarette smoke has emerged as a significant risk factor in the development of asthma and allergic airways disease. The pathogenetic mechanisms are not known, but increased absorption across the airway epithelial lining has been suggested as one possible mechanism of this effect of cigarette smoke. This study examines the absorption-permeability of the nasal epithelial lining in cigarette smokers and non-smokers. For comparison, the effect of a detergent, dioctylsodium sulfosuccinate (DS), is also examined. A solution containing 51Cr-EDTA (51-chromium labeled ethylene diamine tetraacetic acid) (mol. wt. 372 Da) was instilled and maintained in the nasal cavity in six smokers and 12 non-smokers for 15 min. Urine was collected for 24 h after the instillation. The accumulated amount of excreted 51Cr-EDTA was measured and expressed as millilitre nasal instillate. In six non-smokers the procedure was repeated when DS has been added to the instillate. The median recovered amount of 51Cr-EDTA in smokers 0.07 ml (range 0.04-0.32) was not significantly different from that in non-smokers 0.16 ml (0.01-1.22). The recovered amount of 51Cr-EDTA increased from a median of 0.18 ml (0.01-1.22) to 1.13 ml (0.53-1.80) after addition of the detergent (P = 0.028). We conclude that the nasal airway absorption-permeability is not increased in smokers. Hence, passive exposure to cigarette smoke may not produce an impairment of airway barrier functions.

Absorption↗

Glucocorticoid-induced attenuation of mucosal exudation of fibrinogen and bradykinins in seasonal allergic rhinitis.

The mucosal plasma exudate with its proteins, enzymes, derived peptides, and matrix molecules is an important factor in inflammatory airway diseases. This study investigated whether topical glucocorticosteroid treatment influences mucosal exudation of bulk plasma (fibrinogen) and the generation of plasma-derived mediators (bradykinins) in seasonal allergic rhinitis. Twenty-two patients with birch-pollen-induced allergic rhinitis participated in a double-blind, randomized, placebo-controlled study during the birch pollen season in 1989. After a 2-week run-in period, the participants received treatment with budesonide (200 micrograms per nasal cavity and day) or placebo. The patients kept a diary to record their daily nasal symptoms (itching, sneezing, nasal blockage, and secretion). The amount of birch pollen in the air was determined with the aid of a Burkhard pollen trap. A nasal lavage was performed once a week, and the levels of bradykinins and fibrinogen were determined in the lavage fluid samples. The birch pollen season was very mild, resulting in only minor nasal symptoms. In spite of the low pollen exposure, treatment with budesonide reduced the lavage fluid levels of both bradykinins and fibrinogen. The present results show that topical glucocorticosteroid treatment attenuates plasma exudation and the generation of plasma-derived mediators in seasonal allergic rhinitis. This action may not result from simple vascular antipermeability effects of the drug but may rather reflect the anti-inflammatory efficacy of topical glucocorticoids in the airway mucosa.

Administration, Topical↗

Complement activation on the nasal mucosal surface--a feature of the immediate allergic reaction in the nose.

Complement is a system of functionally linked serum proteins that interact to exert biologic effects in inflammatory and immunologic processes. As part of a larger study with a potential topical antiallergic drug, we measured C3a des Arg and C5a des Arg in 13 patients with seasonal allergic rhinitis and in five nonatopic controls after placebo treatment. After 1 week of placebo treatment, a nasal allergen challenge with increasing doses of pollens was performed in both allergic subjects and controls. A symptom score method was used, and in returned nasal lavage fluid, the activity of C3a des Arg and C5a des Arg was measured. We found that allergen challenge in the allergic subjects induced nasal symptoms concomitantly with increased levels of C3a des Arg and C5a des Arg (P < 0.05). No increases either in symptoms or in the very low base-line levels of C3a des Arg and C5a des Arg were observed in the nonallergic controls. We conclude that the activation of the complement cascade is one part of the vasculature exudative response during the immediate allergic reaction in the upper airways. Because of their biologic potency, these proteins may be an essential part of the exudative response which perpetuates the ongoing inflammatory reaction.

Adult↗