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Biomedical subjects

E Andersson

Publications and source records attributed to E Andersson.

At least 55 records · Page 3Linked to original sources

Characteristics of mitral and tricuspid annular velocities determined by pulsed wave Doppler tissue imaging in healthy subjects.

Assessment of myocardial velocities by Doppler tissue imaging is gaining in importance. However, generally accepted reference values are still missing. In this study we examined 62 consecutive healthy subjects (mean age 46, range 22-82 years) by pulsed wave Doppler tissue imaging to characterize the systolic and diastolic velocity profiles of the left and right ventricles. The subjects were divided into 3 different age-groups: group I, younger than 40 years; group II, 40 to 59 years; and group III, 60 years and older. Recordings were made along the long axis in the apical 4- and 2-chamber views by using 4 sites (septal, anterior, lateral, and inferior) at the mitral annulus and 1 site at the tricuspid annulus. Systolic mitral annular velocity (10.3 +/- 1.4 cm/s) correlated strongly with global left ventricular function determined by M-mode echocardiographic mitral annular displacement (r = 0.70, P <.001). The systolic velocity was significantly lower in group III than in group I (9.6 vs 10.8 cm/s, P <.01). A relatively weak, but significant, correlation was found between systolic velocity and the age of the subjects (r = -0.43, P <.001). Mitral annular early diastolic velocity was also lower in group III compared with group I (11.3 vs 17.7 cm/s, P <.001), with a strong correlation with age (r = -0.81, P <.001) and other conventional Doppler diastolic parameters. Both the systolic and early diastolic mitral annular velocities at the septum were lower than at other left ventricular sites. Tricuspid annular systolic velocity (15.2 +/- 1.9 cm/s) was higher than mitral annular systolic velocity (P <.001). Unlike mitral annular velocity, systolic tricuspid annular velocity was not correlated with age. However, the diastolic tricuspid annular velocities correlated well with transtricuspid Doppler diastolic parameters. The method of recording the annular velocities was feasible in all subjects, simple and highly reproducible.

Adult↗

Movement and muscle activity pattern in wheelchair ambulation by persons with para-and tetraplegia.

The patterns of movement and muscle activation in wheelchair ambulation have been studied in two groups: subjects with paraplegia (n = 4) and tetraplegia (n = 3). All subjects were physically active and experienced wheelchair users. The tests were done in the subjects' own wheelchairs and under free-wheeling conditions. The tasks studied were: self-chosen normal velocity, maximal velocity and maximally accelerated start. Muscle activation was registered by surface electromyography performed on several arm and shoulder muscles. The movement pattern was studied by goniometry of the shoulder and elbow joints, as well as by observing video recordings. Speed and arm cycle frequency were also recorded. The movement pattern was divided into three phases: pull, push and recovery. Relatively concordant muscle activation patterns were noted within the groups, whereas differences were noted between the groups with regard to muscle activation, length of the pull and push phases and the velocity-dependent adaptation. The subjects with tetraplegia were more dependent on the pull phase. The self-chosen normal and maximal speeds of the subjects with tetraplegia were approximately half those of the subjects with paraplegia. Three different types of recovery movements were noted as well as a velocity-dependent adaptation. Major trunk movements during the rim phase were only noted at the maximally accelerated start. In conclusion, the results point to both similarities and differences in the movement pattern and muscle activation in individuals with para- and tetraplegia under different ambulation conditions. The differences are of such a magnitude that they are important enough to consider when teaching wheelchair techniques and developing rehabilitation programmes for different groups of patients with spinal cord injuries.

Adult↗

Ultraviolet irradiation depletes cellular retinol and alters the metabolism of retinoic acid in cultured human keratinocytes and melanocytes.

Vitamin A is an intrinsic modulator of proliferation and differentiation in human epidermis, and may be destroyed by ultraviolet radiation (UVR) impinging on the skin. To identify the deleterious effects of a perturbed cellular vitamin A status, we investigated the endogenous retinoid concentrations and the metabolism of [3H]retinol and all-trans [3H]retinoic acid in cultured human keratinocytes and melanocytes exposed to UVR, using high performance liquid chromatography. Before UVR the retinoid content was similar in keratinocytes and melanocytes, but the uptake of [3H]retinol was three-fold higher and the uptake of [3H]retinoic acid was 10-fold higher in the melanocytes. In both cell types, UVR (UVA 360 mJ/cm2 plus UVB 140 mJ/cm2) instantaneously reduced the concentration of retinol by about 50% and that of 3,4-didehydroretinol by about 20%. The retinoid concentrations returned to normal within 1-2 days post-irradiation, despite there being no overt increase in the uptake of [3H]retinol or the biosynthesis of 3,4-didehydroretinol. However, in both types of irradiated cells, the accumulation of the biologically most active metabolite, all-trans [3H]retinoic acid, was about 60% higher than in control cells. Furthermore, the metabolism of authentically supplied [3H]retinoic acid was reduced, especially in irradiated keratinocytes, which probably contributed to the restoration of retinoid levels after UV exposure.

Cells, Cultured↗

Influence of different conditions for tilt compensation on symptoms of motion sickness in tilting trains.

Increased speeds of trains can be achieved by using tilting trains that decrease the lateral acceleration experienced by passengers on curves, thereby allowing trains to run typically 25-30% faster on existing curved track and maintaining good ride comfort. Unfortunately, motion sickness in tilting trains is a major problem for some passengers. To investigate the incidence of motion sickness and the extent to which different tilt compensation strategies influence its occurrence, tests were conducted with a tilting train on a track with a large number of curves. Eighty healthy volunteers were studied, selected partly for their susceptibility. Three different cars were evaluated during 3 test days, with each test ride lasting about 3 h. On four occasions per test ride, the subjects answered a questionnaire concerning activities during the ride, ride comfort, ability to work and read, vegetative symptoms, fatigue, sleepiness, nausea and well-being. Subjects estimation of average ride comfort and ability to work and read was good in all conditions. However, 10% of the test subjects reported various symptoms of motion sickness (SMS). A 55% degree of tilt compensation of the lateral acceleration instead of the normal 70% reduced the symptoms of motion sickness incidence (SMSI) by 25-40%. SMSI correlated poorly with motion doses, which integrates vertical or lateral acceleration but correlated well with roll acceleration motion dose (r2 = 0.43, p < 0.001). For women, riding backward (p < 0.001) minimized SMSI, but men were insensitive to direction. Future railway design will have to optimize tilt systems by both minimizing motion sickness and avoiding excessive lateral acceleration or jerk.

Adult↗

The role of the propeptide for processing and sorting of human myeloperoxidase.

Myeloperoxidase (MPO), stored in azurophil granules of neutrophils, is critical for an optimal oxygen-dependent microbicidal activity of these cells. Pro-MPO goes through a stepwise proteolytic trimming with elimination of an amino-terminal propeptide to yield one heavy and one light polypeptide chain. The propeptide of MPO may have a role in retention and folding of the nascent protein into its tertiary structure or in targeting of pro-MPO for processing and storage in granules. A propeptide-deleted pro-MPO mutant (MPODeltapro) was constructed to determine if deletion of the propeptide interferes with processing and targeting after transfection to the myeloid 32D cell line. Transfection of full-length cDNA for human MPO results in normal processing and targeting of MPO to cytoplasmic dense organelles. Although the efficiency of incorporation was lower for MPODeltapro, both pro-MPO and MPODeltapro showed heme incorporation indicating that the propeptide is not critical for this process. Deletion of the propeptide results in synthesis of a protein that lacks processing into mature two-chain forms but rather is degraded intracellularly or secreted. The finding of continued degradation of MPODeltapro in the presence of lysosomotrophic agents or brefeldin A rules out that the observed degradation takes place after transfer to granules. Intracellular pro-MPO has high mannose oligosaccharide side chains, whereas stored mature MPO was found to have both high mannose and complex oligosaccharide side chains as judged by only partial sensitivity to endoglycosidase H. The propeptide may normally interfere with the generation of certain complex oligosaccharide chain(s) supported by the finding of high mannose side chains in secreted pro-MPO and lack of them in MPODeltapro that contained complex oligosaccharide side chains only. In conclusion, elimination of the propeptide of pro-MPO blocks the maturation process and abolishes accumulation of the final product in granules suggesting a critical role of the propeptide for late processing of pro-MPO and targeting for storage in granules.

Animals↗

Evolutionary stability of the immunoglobulin heavy chain variable region gene families in teleost.

A comparison between related species would allow us to study the evolutionary changes in complex gene families. To investigate the evolution of immunoglobulin VH gene families in lower vertebrates, we compared cDNA VH clones from two related teleost fish species, Arctic charr (Salvelinus alpinus) and rainbow trout (Oncorhynchus mykiss), which are separated from their common ancestor by 12-20 million years (MY). The results showed that randomly isolated charr VH genes could be closely grouped to known VH genes of rainbow trout, suggesting that the VH family structure is stable during 12-20 MY and that the total number of VH families changes only gradually over a longer period. This finding also led us to define eight VH gene families of Arctic charr, designated Salalp VH I, VH II, and so on. The presence of species-specific amino acids suggests that non-reciprocal genetic exchanges (e.g., gene duplication) play an important role in shaping the evolution of the V gene family.

Amino Acid Sequence↗

Endothelin-induced contractions in placental arteries is mediated by both ETA- and ETB-receptors.

We have examined the contractile response to the vasoconstrictor endothelin-1 (ET-1) in uteroplacental arteries from normal pregnant women in the presence and absence of specific ET-receptor antagonists and agonists, and the vasodilator nitric oxide. Segments of placental arteries (n = 97) obtained from 37 placentas immediately after delivery were mounted in organ baths superfused with Krebs-Ringer solution at 37 degrees C. The tension was recorded isometrically and registered on a polygraph. We found that the placental artery segments responded to ET with a dose-dependent vasoconstriction. Half-maximal response was obtained at 2.6 x 10(-8) M. At 10(-7) M, the contractile response was 52% of the maximum KCl-response. The ET-1 induced contraction at 10(-7) M was inhibited by 74% after addition of the ETA-antagonist BQ-123 (10(-6) M), and by 58% by the ETB-antagonist BQ-788 (10(-6) M). Both BQ-123 and BQ-788 almost completely abolished the response to ET (10(-7) M). The selective ETB-agonist IRL-1620 also elicited vasoconstriction in the placental artery with a half maximal response at 8 x 10(-7) M. On a molar basis at 10(-7) M, the contraction by IRL-1620 as compared to ET was 30-fold lower. The contractile response of IRL-1620 (10(-6) M) was inhibited by 99% by BQ-788 (10(-6) M). After pre-contraction of the placental arteries with ET-1 (10(-7) M), the vessels relaxed in response to the nitric oxide donor, nitroglycerin (10(-6) M). The present results show that ET-1 contracts placental arteries through both ETA- and ETB-receptor activation. Nitric oxide (10(-6) M) was able to relax more than half of the initial ET-1 contraction, indicating that nitric oxide may be an important vasodilator in the placenta.

Adult↗

Autonomic nervous influence of the female guinea-pig urinary bladder during the oestrus cycle.

The mammalian urinary bladder receives dual innervation. The excitatory innervation is considered to be partly cholinergic and partly mediated via NANC-receptors. Several (co-)transmitters have been suggested. The adrenergic inhibitory innervation is mediated via alpha- and beta-receptors. Female sex hormones could change autonomic influence of urogenital organs. It was considered to be of interest to characterize the spontaneous and nerve stimulation-induced muscular activity in the urinary bladder of the female guinea-pig during the oestrus cycle. Both the spontaneous activity and nerve-induced activity varied according to the hormonal status of the animal. An alpha-adrenergic inhibitory influence was identified. It was further confirmed that the excitatory innervation could not be blocked by the cholinergic antagonist scopolamine, while alpha-beta-methylene ATP partly inhibited nerve stimulation-induced smooth muscle response, most prominent at cycle day 6. Indomethacin did not impair spontaneous activity or nerve stimulation-induced activity. Nitric oxide reduced nerve stimulation-induced responses on cycle day 12. Imperative urinary bladder contractions are reported to diminish after oestrogen use and in the female a hormonal effect of the nervous influence on the urinary bladder smooth muscle is suggested.

Adenosine Triphosphate↗

The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis.

The study was undertaken to investigate a possible mechanism for reducing the phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women suffering from endometriosis. Peritoneal fluids were collected during laparoscopy from women undergoing laparoscopic sterilization or from women under investigation for cause of infertility where the laparoscopic findings were endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro with peritoneal fluid with or without lignocaine. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leukocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte. For patients with endometriosis, treatment with lignocaine might be a means of increasing the chances of conception. A clinical study is in progress to evaluate this effect in vivo and to search for alternative methods of assisting the fertilization process.

Adult↗

Phorbol esters and synthetic diacylglycerols inhibit gamma-aminobutyric acid uptake in human spermatozoa: an effect mediated by protein kinase C?

Protein kinase C (PKC) and protein kinase A (PKA) are present in human spermatozoa and probably involved in the cascade systems leading to acrosomal exocytosis. We have investigated the possibility that these two protein kinases are involved in the regulation of gamma-aminobutyric acid (GABA) uptake in human spermatozoa. Swim-up preparations of human spermatozoa were exposed to phorbol 12-myristate 13 acetate (PMA) and 1-oleoyl-2-acetyl-sn-glycerol (OAG), which are activators of PKC, and to dibutyryl cyclic AMP (dbcAMP), a PKA activator, and subsequently incubated with radiolabelled GABA. Accumulated intracellular GABA was measured in a scintillation counter. Both PMA and OAG caused inhibition of GABA uptake while dbcAMP was without effect. The inhibitory effect on GABA uptake observed following exposure to the PKC activators could, however, not be counteracted by preincubation of the sperm samples with the PKC inhibitors staurosporine or H-7. The inhibitory effect on GABA uptake following addition of PMA was enhanced by prolonged exposure to the reagent and by increased capacitation prior to addition of the reagent. A small numerical increase in the percentage of acrosome-reacted cells was observed following exposure of the sperm cells to the highest concentrations of PMA, OAG and dbcAMP. No sperm motility parameters were affected by the treatment protocols as measured using computer-assisted semen analysis (CASA).

Diglycerides↗

Effects of gonadectomy and androgen treatments on pituitary and plasma levels of gonadotropins in mature male Atlantic salmon, Salmo salar, parr--positive feedback control of both gonadotropins.

The aim of the present study was to clarify the role of feedback control on the (brain)-pituitary-gonadal axis in regulating FSH (gonadotropic hormone, GTH I) and LH (GTH II) in natural maturation in salmonids. In two experiments, 2-yr-old previously mature Atlantic salmon male parr were castrated or sham operated in the spring following their first reproductive season. In one of the experiments, castrated fish were also implanted with silicone elastomer capsules containing testosterone (T) or 11-ketoandrostenedione (11KA). The fish were sampled in July, September, and November (spawning period). Pituitary and plasma LH and FSH levels were measured using RIA and were lower in castrated than in sham-operated fish, indicating positive feedback on both FSH and LH. T, and to a lesser extent 11KA, increased pituitary LH content in castrated fish. The 11KA increased plasma and pituitary FSH levels, whereas T suppressed FSH in July and stimulated it in November. Plasma FSH levels peak earlier than LH, and it is suggested that if one or more feedback effects are involved in controlling the "all-or-nothing response," i.e., whether a fish will mature or not, a feedback effect on FSH is the most likely candidate.

Androstenes↗

Analgesic use disorders among orthopedic and chronic pain patients at a rehabilitation clinic.

Interviews were conducted with 265 orthopedic and chronic pain patients, using a structured diagnostic instrument (ADDIS/SUDDS) concerning their use of analgesics. Twenty-two percent of the patients met criteria for analgesic use disorders in accordance with DSM-III-R; 18.5% fulfilled DSM-IV criteria. Dextropropoxyphene was the most common analgesic prescribed and was used by 47% of the patients who met criteria for analgesic use disorders. It is concluded that patients with chronic pain using narcotic analgesics are at considerable risk of developing analgesic use disorders. Assessment of the use of analgesics should be offered to pain patients taking narcotic drugs.

Adult↗

Mortality from asthma and cancer among sulfite mill workers.

OBJECTIVES: The aims of the present case-referent study were to investigate whether sulfite workers show increased mortality from asthma, chronic obstructive pulmonary disease or certain malignancies of interest in relation to sulfite mill work. The main exposure from the pulping processes is from sulfur dioxide, wood dust and terpenes. METHODS: The subjects of the study were all the men who died between 1960 and 1989 and who were aged 40 to 75 years at death (N = 780) in the parishes surrounding 3 sulfite mills. The men who died from asthma (N = 13), COPD (N = 20), lung cancer (N = 33), stomach cancer (N = 35), or brain tumor (N = 10) formed the case group. All the subjects, except the cases in question, were used as referents. As a proxy variable of exposure, job titles from the registers of deaths and burials were used, and 24% of the subjects were classified as exposed. RESULTS: There was an increased mortality from asthma [odds ratio(OR) 2.8, 90% confidence interval (90% CI) 1.1-6.8] and brain tumors (OR 3.3, 90% CI 1.2-8.9) among the sulfite workers. The mortality due to lung cancer was not significantly increased (OR 1.4, 90% CI 0.7-2.6), and there was a reduced mortality from stomach cancer (OR 0.4, 90% CI 0.2-0.9). CONCLUSIONS: The increased asthma mortality may be due to accidental exposure to irritating gases, such as sulfur dioxide. The increased risk for brain tumors has no obvious explanation.

Adult↗

Induction of antigen-specific isotype switching by in vitro immunization of human naive B lymphocytes.

The use of in vitro immunization technology for the generation of human antigen-specific antibodies has essentially resulted in low affinity IgM antibodies, resembling an in vivo primary immune response. We now describe a detailed reproducible protocol for a two-step in vitro immunization, which yields isotype switched, antigen-specific human antibodies. The immunizing antigen was a 30aa synthetic peptide, containing both a B (15aa V3 peptide of the HIV-1) and a T helper cell epitope (15aa peptide from tetanus toxin). The immunization protocol includes: (i) a selection procedure of donors with a memory T cell response against tetanus toxoid; (ii) immunization of mature naive peripheral B lymphocytes in two distinct phases, involving a primary and a secondary step. None of the donors which were examined after primary immunization showed at any time an IgG anti-V3 specific antibody response, while all the donors showed an IgM response. After the secondary immunization step, anti-V3 antibodies of both IgM and IgG isotypes were detected. The switch frequency event was high among the tested donors (5/8).

Amino Acid Sequence↗

Analysis of VH gene diversity in rainbow trout (Oncorhynchus mykiss): both nonsynonymous and synonymous nucleotide changes are more frequent in CDRs than in FRs.

Forty-six immunoglobulin VH gene sequences of rainbow trout were compiled to analyze the extent of variations and the frequency of nucleotide changes in CDRs and FRs. The results show that the frequency of nonsynonymous (amino acid replacing) changes (Ka) are on average 4.9 times higher in complementarity determining regions (CDRs) than in FRs, thus contributing more diversity in CDRs. Unexpectedly, however, the frequency of synonymous (silent) changes (Ks) show the same tendency: it was 5.3 times higher in CDRs than in framework regions (FRs). The distribution of Ks/Ka ratios of each comparison shows no segregation between CDRs and FRs. The same analysis applied to five germline VH genes of Heterodontus francisci shows the same result as was found with the rainbow trout. In contrast, the results from mouse data show that, while the CDR/FR ratio for Ka is much higher (7.4), the CDR/FR ratio for Ks is only slightly higher (1.8). The distribution of Ks/Ka ratios in mouse indicates clear segregation between CDRs and FRs. This suggests that CDR germline diversity is largely generated by gene conversion in VHs of lower vertebrates such as rainbow trout or shark. This mechanism might be advantageous to lower vertebrates in generating V gene diversity faster than other mechanisms such as point mutation and selection.

Animals↗

Vitamin A metabolism and mRNA expression of retinoid-binding protein and receptor genes in human epidermal melanocytes and melanoma cells.

Retinoids inhibit proliferation of melanocytes and melanoma cells and affect disorders of hypo- and hyperpigmentation. Such effects might involve retinoid-binding proteins, retinoid metabolites and nuclear retinoid receptors for transcriptional activation. We detected messenger RNA transcripts for the cellular retinol- and retinoic acid-binding proteins (CRBP, CRABP I and II) in cultured epidermal melanocytes. In the melanoma cell lines the major transcript was CRABP II. Nuclear retinoic acid (RA) receptor transcripts and the 9-cis-retinoic acid receptor transcript were detected in all cells. The endogenous concentrations of retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) in melanocytes were five times those in melanoma cells. When cells were incubated with [3H]ROH the main metabolites in the melanocytes were [3H]ddROH (4%) and [3H]RA (0.4%). Formation of [3H]RA was only detected in one melanoma cell line. Both melanocytes and melanoma cells produced an unidentified metabolite when incubated with [3H]ROH and [3H]RA. Dissimilarities in the metabolism and endogenous concentration of retinoids between benign and malignant melanocytes might play a key role in differentiation and growth regulation.

Cells, Cultured↗

Biosynthesis, processing and sorting of neutrophil proteins: insight into neutrophil granule development.

Neutrophil granulocytes are specialized phagocytic cells that carry a collection of granules for regulated secretion, each with distinct constituents. The granules can be classified as azurophil (primary), developed first, followed in time by specific (secondary) granules gelatinase granules, and secretory vesicles. Stage- and tissue-specific transcription factors govern the successive expression of genes for granule proteins to allow storage of the gene products in these organelle categories whose packaging is separated in time. Many of the granule proteins, in particular those of the heterogeneous lysosome-like azurophil granules, are subject to extensive post-translational proteolytic processing into mature proteins, most commonly as a post-sorting event. A selective aggregation of proteins destined for storage in granules, as discussed in this review, would facilitate their retention and eliminate a need for distinct sorting motifs on each granule protein. Aggregation of granule proteins, that are often cationic, would be assisted by the anionic serglycin proteoglycans present in neutrophils. The antibacterial granule proteins can serve as models for antibiotics and some of them possess a potentially useful therapeutic ability to bind and neutralize endotoxin. Because aberrant expression of transcription factors regulating the synthesis of granule proteins is often found in leukemia, the clarification of mechanisms regulating the timed expression of granule proteins will shed light on the maturation block in myeloid leukemias.

Animals↗