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Biomedical subjects

S Karlsson

Publications and source records attributed to S Karlsson.

At least 127 records · Page 7Linked to original sources

Movement and signal analysis by means of a computer-assisted system.

The aim of this study was to evaluate the suitability of an optoelectronic system for recording mandibular movements and the conformity of simultaneous recordings of the electromyographic activity in the masseter, the temporal and the suprahyoid muscles. A simulator test to identify the inherent noise of the MacReflex motion analysis system was performed by means of a micrometer screw. The test showed a very small noise inherent in the clinical set-up of the monitoring system. The values obtained also reflected external vibrations. A clinical pilot study was performed to find a feasible site for attaching the reflective markers, either to the incisal teeth of the mandible or as chin marker. In tests including the muscle activity, the conformity between the curves of the movement and muscle activity was good. The method was easy to use in clinical tests, the software of the system reduced the analysis time to a minimum and a number of variables could be measured with a high degree of precision.

Artifacts↗

Physical restraints in geriatric care in Sweden: prevalence and patient characteristics.

OBJECTIVE: Physical restraints are used frequently in geriatric care to promote the safety of frail older patients. This study investigated the prevalence of the use of physical restraints in geriatric care and the way in which patient characteristics are related to the use of physical restraints. DESIGN: A point prevalence study of patients cared for in various types of geriatric settings. SETTING: Eight nursing homes, 15 old people's homes, a somatic geriatric clinic, and a psychogeriatric clinic in a health care district in northern Sweden. PARTICIPANTS: A total of 1325 patients, mean age 82 years, 64% of whom were women. MEASUREMENTS: The Multi-Dimensional Dementia Assessment Scale (MDDAS) was used to measure motor function, vision, hearing, speech, ADLs, behavioral symptoms, psychiatric symptoms, use of psychoactive drugs, and the physical and psychological workload of the staff. In addition, questions concerning the use of physical restraints were added to the instrument. RESULTS: Twenty-four percent of the patients were physically restrained. The highest prevalence was found in nursing homes and psychogeriatric care. Physical restraints were found to relate most strongly to cognitive impairment, impaired ADLs, and speech and walking ability. Ninety-four percent of the restrained patients were cognitively impaired. Other variables relating to the use of physical restraints were psychiatric symptoms and behavioral disturbances. CONCLUSIONS: This study has shown that physical restraints are used frequently in geriatric care in Sweden and that cognitive and physical impairments relate very closely to the use of physical restraints.

Activities of Daily Living↗

Signaling mechanisms underlying the insulinotropic effect of pituitary adenylate cyclase-activating polypeptide in HIT-T15 cells.

The signaling mechanisms underlying the insulinotropic effect of the pancreatic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) were studied in insulin-producing HIT-T15 cells. It was found that unlabeled PACAP38 dose-dependently displaced [125I]PACAP27 from HIT-T15 cell membranes, showing binding of the peptide to these cells. Furthermore, at levels above 0.1 nM, PACAP38 stimulated insulin secretion in a Ca2+ -dependent manner, requiring 0.5 mM glucose. The peptide also markedly increased the cellular cAMP content and slightly stimulated the formation of inositol phosphates. Moreover, PACAP38 elevated the cytoplasmic Ca2+ concentration ([Ca2+]cyt) in fura-2-AM-loaded cell suspensions. The PACAP38-induced increase in cellular cAMP content was also seen at zero glucose, whereas the increases in insulin secretion and [Ca2+]cyt were abolished by removal of glucose or extracellular Ca2+. We conclude that PACAP38 binds to HIT-T15 cell membranes and acts in a glucose-dependent manner on adenylate cyclase to form cAMP, which both directly and indirectly, through increased [Ca2+]cyt, stimulates exocytosis.

Animals↗

A 3-year clinical follow-up study of a ceramic (Optec) inlay system.

To evaluate the clinical quality of ceramic (Optec) inlays, the inlay production of 10 dentists, served by 3 dental laboratories, was examined independently by 2 calibrated examiners. Of the 57 patients with 205 inlays participating in the first examination, 47 patients with 145 remaining inlays participated in the 3-year follow-up reexamination. For 14 of the participants in the reexamination, altogether 21 inlays had fractured. The mean time in service before fracture was 26.4 months (range, 12-53 months). The inlays were rated using the California Dental Association (CDA) quality evaluation system. This examination showed that the mismatch of color had increased from the first examination to the reexamination and registered slightly roughened surfaces. As to anatomic form, a reduced number of inlays did not receive an excellent CDA rating at the reexamination. Visible evidence of ditching along the margin had increased by almost 50%, and an apparent discoloration of the margin between the restoration and the tooth structure was seen in 73% of the reexamined inlays, compared with 7% at the first examination.

Adolescent↗

Axial wall convergence of full veneer crown preparations. Documented for dental students and general practitioners.

The convergence angle in 478 full crown preparations was assessed. Of these preparations, 351 had been performed by general practitioners and 127 by dental students. Groups of preparations performed on incisors, premolars, and molars were compared, as were preparations performed by dentists and students. Two different convergence angles were measured for each tooth, buccolingually and mesiodistally. The results showed a mean angle of 21 degrees. The mean values for premolars and molars differed significantly. When a comparison was made of preparations performed by students, a significant difference was found between premolars and molars. The same comparison for general practitioners showed a significant difference both for incisors compared with molars and for premolars compared with molars. A wide range was found for the convergence of the axial walls, especially for the preparations performed by general practitioners.

Clinical Competence↗

A two-year dietary carcinogenicity study of the antiestrogen toremifene in Sprague-Dawley rats.

The carcinogenic potential of the nonsteroidal triphenylethylene antiestrogen toremifene (Fareston) was evaluated in a standard 104-week rat dietary carcinogenicity study. The doses were 0, 0.12, 1.2, 5.0 and 12 mg/kg/day and the number of animals 50/sex/dose group. The body weight gain and food consumption were monitored once weekly (study weeks 1-16) or once every four weeks thereafter (study weeks 17-104). Blood samples were taken at weeks 34, 52 and 104 and the plasma concentrations of toremifene, as well as the two main metabolites (deaminohydroxy)toremifene and N-demethyltoremifene, were measured. All doses of toremifene reduced food intake and body weight gain. Toremifene caused a significant reduction in mortality, which was mainly due to reduced incidences of pituitary tumors. This was evident in all dose groups. Drug-related decrease of mammary tumors in females (at all doses) and testicular tumors in male rats (doses > or = 1.2 mg/kg/day) were also evident. The incidence of the preneoplastic foci of basophilic hepatocytes were significantly decreased in treated female groups. Toremifene induced no preneoplastic or neoplastic lesions. Based on histopathology, no obvious toxicity could be observed. Drug-related changes were observed in the genital organs, thyroid, spleen, mammary gland, adrenal, kidney, stomach and lung. These changes were due to hormonal disturbances or as a result of reduced food consumption or reduced incidences of pituitary, mammary or testicular tumors. This study indicates that toremifene is an efficient antiestrogen in long-term treatment, is well tolerated and has no tumorigenic potential in rats.

Aging↗

Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors.

The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease. We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus. The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells. The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced NIH 3T3 cells and Gaucher skin fibroblasts. These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24. Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population, demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured. The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity). Efficient transduction of CD34+ hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive. The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected.

3T3 Cells↗

Transfer of the human glucocerebrosidase gene into hematopoietic stem cells of nonablated recipients: successful engraftment and long-term expression of the transgene.

In trying to develop methods of gene therapy for Gaucher disease that will avoid the morbidity and mortality associated with bone marrow (BM) ablation, we transplanted BM stem cells transduced with a retroviral vector containing the human glucocerebrosidase cDNA into normal, nonablated, syngeneic mice. Donor BM from untreated male mice or treated with 5-fluorouracil (5-FU) was transduced ex vivo using a standard 4-day transduction protocol. Recipient female mice were injected one time only or once daily for 5 consecutive days or once a week for 5 consecutive weeks using 2 x 10(7) (untreated BM) or 2 x 10(6) (5-FU-treated BM) cells per injection. Initial transduction efficiency into colony-forming unit-spleen (CFU-S) was 80% to 100%. Recipient analysis was performed at least 6 months after the last transplantation. The best engraftment of donor stem cells, up to 5% by secondary CFU-S analysis, was obtained with multiple injections of transduced BM not previously treated with 5-FU. Polymerase chain reaction (PCR) amplification for both the transgene and the Y chromosome identified the progeny of transduced stem cells in various hematopoietic and non-hematopoietic organs. The copy number of the transgene in stem cells was 0.13 to 2.8. Transgene expression was shown by reverse transcriptase-PCR, in situ hybridization, and immunohistochemistry. No serious side effects of the procedure were noted. We conclude that multiple transplants of retrovirally transduced BM cells into nonablated recipients may be a safe and effective therapeutic modality for a number of genetic hematopoietic disorders.

Animals↗

Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients.

We have achieved high-efficiency gene transfer into nonmobilized peripheral blood (PB) CD34+ cells from patients with Gaucher's disease using a clinically acceptable retroviral supernatant transduction protocol. In our studies, bone marrow (BM) and PB CD34+ cells were transduced using a high titer (10(8) particles/mL) retroviral supernatant once a day for 4 consecutive days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), with or without an irradiated allogeneic BM stromal layer. The growth factors alone resulted in 29% +/- 10% gene transfer of PB CD34+ clonogenic cells in contrast with 71% +/- 17% gene transfer efficiency using stroma with the growth factors; a 2.5-fold increase. The increase in gene transfer efficiency was less prominent when BM CD34+ cells were used (40% +/- 16% without and 57% +/- 8% with stroma, a 1.5-fold increase). The overall transduction efficiency of both PB and BM CD34+ cells was lower when the cells were transduced over a stromal cell layer without added growth factors. The combination of IL-3, IL-6, and SCF with stroma transduced 75% of primitive long-term culture initiating cells (PB LTC-ICs) in comparison with 34% of LTC-ICs when IL-3, IL-6, and SCF were used without stromal support. Using this clinically acceptable supernatant/cytokines/stroma transduction protocol, correction of the glucocerebrosidase (GC) deficiency in the progeny cells of PBLTC-ICs from Gaucher's-disease patients has been accomplished. Efficient transduction of the PB CD34+ cells using this transduction protocol may allow repeated delivery of "GC-corrected" hematopoietic stem and progenitor cells to Gaucher's-disease patients.

Antigens, CD↗

Involvement of nitric oxide in neuroglycopenia-induced insulin and glucagon secretion in the mouse.

Neuroglycopenia induced by administration of 2-deoxy-D-glucose is known to stimulate the secretion of both insulin and glucagon in mice by a mechanism that is dependent on neural activity. In the present study, we examined whether the neurotransmitter nitric oxide (NO) is involved in this process. Therefore, 2-deoxy-D-glucose (500 mg/kg) was injected intravenously alone or together with the inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (50 mg/kg) to conscious mice. It was found that NG-nitro-L-arginine methyl ester inhibited the increased plasma levels of both insulin (by 26%; P = 0.039) and glucagon (by 45%; P < 0.001) at 10 min after injection of 2-deoxy-D-glucose. Similarly, the NO synthase inhibitor, NG-nitro-L-arginine, which is devoid of the anticholinergic property of NG-nitro-L-arginine methyl ester, inhibited the responses of both insulin (by 53%; P = 0.026) and glucagon (by 57%; P = 0.003) to 2-deoxy-D-glucose. In contrast, the stereoisomer of NG-nitro-L-arginine methyl ester, NG-nitro-D-arginine methyl ester, which is devoid of NO synthase inhibitory activity, was without effect on 2-deoxy-D-glucose-induced insulin and glucagon secretion. Plasma levels of adrenaline and noradrenaline after administration of 2-deoxy-D-glucose were also reduced by NG-nitro-L-arginine methyl ester. In contrast, the insulin and glucagon secretory responses to intravenous injection of arginine (250 mg/kg), glucose (500 mg/kg) or the cholinergic agonist, carbachol (30 micrograms/kg), were not influenced by NG-nitro-L-arginine methyl ester, NG-nitro-D-arginine methyl ester or NG-nitro-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Long-term in vivo expression of the human glucocerebrosidase gene in nonhuman primates after CD34+ hematopoietic cell transduction with cell-free retroviral vector preparations.

Successful gene transfer into stem cells would provide a potentially useful therapeutic modality for treatment of inherited and acquired disorders affecting hematopoietic tissues. Coculture of primate bone marrow cells with retroviral producer cells, autologous stroma, or an engineered stromal cell line expressing human stem cell factor has resulted in a low efficiency of gene transfer as reflected by the presence of 0.1-5% of genetically modified cells in the blood of reconstituted animals. Our experiments in a nonhuman primate model were designed to explore various transduction protocols that did not involve coculture in an effort to define clinically useful conditions and to enhance transduction efficiency of repopulating cells. We report the presence of genetically modified cells at levels ranging from 0.1% (granulocytes) to 14% (B lymphocytes) more than 1 year following reconstitution of myeloablated animals with CD34+ immunoselected cells transduced in suspension culture with cytokines for 4 days with a retrovirus containing the glucocerebrosidase gene. A period of prestimulation for 7 days in the presence of autologous stroma separated from the CD34+ cells by a porous membrane did not appear to enhance transduction efficiency. Infusion of transduced CD34+ cells into animals without myeloablation resulted in only transient appearance of genetically modified cells in peripheral blood. Our results document that retroviral transduction of primate repopulating cells can be achieved without coculture with stroma or producer cells and that the proportion of genetically modified cells may be highest in the B-lymphoid lineage under the given transduction conditions.

Animals↗

Structural organization, expression and chromosomal mapping of the mouse cystatin-C-encoding gene (Cst3).

Cystatin C (CstC) is a potent cysteine-proteinase inhibitor. The structure of the mouse CstC-encoding gene (Cst3) was examined by sequencing a 6.1-kb genomic DNA containing the entire gene, as well as 0.9 kb of 5' flanking and 1.7 kb of its 3' flanking region. The sequence revealed that the overall organization of the gene is very similar to those of the genes encoding human CstC and other type-2 Cst, with two introns at positions identical to those in the human gene. The promoter area does not contain typical TATA or CAAT boxes. Two copies of a Sp1-binding motif, GGGCGG, are present in the 5' flanking region within 300 bp upstream from the initiation codon. A hexa-nucleotide, TGTTCT, which is a core sequence of the androgen-responsive element (ARE), is found in the promoter region. This region also contains a 21-nucleotide sequence, 5'-AGACTAGCAGCTGACTGAAGC, which contains two potential binding sites for the transcription factor, AP-1. The mouse Cst3 mRNA was detected in all of thirteen tissues examined by Northern blot analysis. Cst3 was mapped in the mouse to a position on distal chromosome 2.

Amino Acid Sequence↗

Knee extension torque and intramuscular pressure of the vastus lateralis muscle during eccentric and concentric activities.

The objectives of this study were to determine whether the occurrence of delayed onset muscle soreness (DOMS) for the vastus lateralis muscle was associated with elevated intramuscular pressure (IMP); and to assess, whether high eccentric forces occurred at an increased muscle length (as determined by joint angle). Therefore, peak knee extension torque, peak IMP of the vastus lateralis muscle, and the joint angle at which peak torque (JAPT) occurred were determined in eight male subjects during repetitive eccentric and concentric activities until fatigue occurred. Peak torque was significantly higher for eccentric compared to concentric activity (P < 0.01) and declined significantly for both activities (P < 0.01) throughout the protocols. When comparing the start (prior to fatigue) to the end (fatigue state), mean torque for eccentric activity declined from 191 to 147 (N.m) and for concentric activity declined from 166 to 104 (N.m). In contrast, peak IMP was not significantly different between the types of activity and did not change significantly with time. At the start and the end, the mean IMP remained constant for eccentric activity at 54 mmHg (7.2 kPa) but for concentric activity was 78 mmHg (10.4 kPa) and 96 mmHg (12.8 kPa), respectively. All the subjects, however, experienced DOMS of the vastus lateralis muscle exclusively for the eccentric activity leg. The JAPT was not different between activity types and did not change significantly with time; however, a significant interaction between activity type and time was observed (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Survival rate and failure characteristics for two post designs.

The dental records of 638 patients treated with 788 posts and cores were studied to analyze failure rate and failure characteristics for two post designs. Frequency of the technical failures, loss of retention, root fracture, and post fracture were recorded 4 to 5 years after post cementation. There were two types of posts: custom-cast tapered posts and parallel-sided serrated posts. The cumulative failure rate was 15% for 456 tapered posts and 8% for 332 Para-Post posts. Loss of retention was the most frequent reason for failure for both types of posts, whereas root fractures had the most serious consequences, and all resulted in extraction. A significantly higher success rate was recorded for parallel-sided serrated posts, compared with custom-cast posts, regarding the total failure rate and the severity of the failure (p < 0.05).

Dental Abutments↗

Stimulation of endocrine, but not exocrine, pancreatic secretion during 2-deoxy-D-glucose-induced neuroglycopenia in the conscious pig.

The effects of autonomic nervous activation, initiated by 2-deoxy-D-glucose (2-DG)-induced neuroglycopenia, or endocrine and exocrine pancreatic secretion were investigated in the conscious pig. Pigs were surgically fitted with permanent pancreatic duct and duodenal reentrant cannulas, allowing long-term sampling of pancreatic juice, and a jugular vein catheter for blood sampling and infusion of 2-DG. 2-DG was administered as a 5-min intravenous infusion at three dose levels to conscious pigs. 2-DG (400 mg/kg) was found to elevate plasma glucagon and insulin levels (p < 0.01). In contrast, exocrine pancreatic secretion, measured as volume, total protein output, and output of trypsin activity was not affected by 2-DG at the dose levels of 75, 200, and 400 mg/kg. Secretin (440 pmol/kg/h), however, stimulated pancreatic exocrine output of fluid (p < 0.01), protein (p < 0.01), and trypsin (p < 0.05). It is concluded that autonomic nervous activation by 2-DG-induced neuroglycopenia, in the conscious pig under basal conditions, elevates the plasma levels of glucagon and insulin but does not affect exocrine pancreatic secretion. 2-DG-induced neuroglycopenia is, thus, a suitable model for studying autonomic neural influences on the porcine endocrine pancreas.

Animals↗

Effects of gold and bonded ceramic inlays on the ability to perceive occlusal thickness.

Any crown or inlay preparation will be accompanied with pulpal involvement and possible altered biomechanical and/or viscoelastic properties concerning the treated tooth. This study was aimed to assess this influence in terms of differences in interocclusal discrimination threshold value, before and after rehabilitation with gold inlays and by composite resin bonded ceramic inlays. Twenty patients were included and treated with one gold and three ceramic inlays each. For purposes of determining the discrimination threshold between the inlays and antagonizing teeth, plastic foils of different thicknesses were used. Each inlay position, as well as a pair of control teeth, were tested before and after treatment. Before rehabilitation an interocclusal and discrimination threshold of 24 microns at the level of 80% right answers were determined. Treatment with inlays, however, resulted in a significantly different and increased threshold for every tooth/inlays combination. No significant differences between the sessions were recorded for the control teeth. It could be concluded that, in the short term, an oral rehabilitation with inlays and in particular bonded inlays will influence mechanosensitive afferents.

Adult↗

Ceramic inlay systems: some clinical aspects.

Due to their inertness and unsurpassed aesthetic properties, ceramic materials are increasingly used as inlay materials. Based on a questionnaire, the frequency and character of complications related to ceramic inlay therapy were assessed and some important pitfalls and clinical relevant factors discussed. A majority of the dentists performed between 1 and 10 ceramic inlays per month using several different ceramic materials. As many as 85% of the dentists had observed complications in connection with ceramic inlays. Most frequency reported was hypersensitivity of a transient nature (15%). The material revealed an overall inlay fracture frequency of 5%, but the individual variations were high. Tooth fracture, loss of retention and other complications such as secondary caries, endodontic envolvement, colour mismatch and a surface and edge deterioration occurred with a varying but lower frequency. Failure analysis revealed a large number of causative factors among which cavity and inlay design, bonding procedures, selection of luting material and proper case selection were regarded as the most important. Due consideration to the strength of remaining tooth substance was found to be important in reducing the problem of hypersensitivity and the risk of tooth and inlay fracture.

Dental Caries↗