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Biomedical subjects

F Jessen

Publications and source records attributed to F Jessen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Genetic polymorphism of cathepsin D is strongly associated with the risk for developing sporadic Alzheimer's disease.

The beta amyloid peptide derives from its precursor protein via proteolytic cleavage of yet unidentified proteases (beta- and gamma-secretases). Cathepsin D is an intracellular protease with in-vitro beta-secretase-like features. An exonic polymorphism of the cathepsin D gene (alanine to valine transition at position 224, exon 2) has been associated with altered enzyme function. We tested the hypothesis that this polymorphism is associated with an increased risk for Alzheimer's disease in 102 demented patients, 191 healthy subjects, and 160 depressed patients. There was a highly significant overrepresentation of the cathepsin D*T allele in demented patients (14.2%) compared to non-demented controls (6.7%, P = 0.0012). Carriers of the cathepsin D*T allele had a 2.4-fold increased risk for developing AD than non-carriers. Carriers of the apolipoprotein E epsilon 4 allele had a 4.1 -fold increased risk than non-carriers. The odds ratio for subjects with the apolipoprotein E epsilon 4 and the cathepsin D*T allele was 5.9. Our data suggest that the cathepsin D genotype is strongly associated with the risk for Alzheimer's disease.

Aged↗
PubMed1999

Functional MRI of cerebral activation during encoding and retrieval of words.

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.

Adult↗
PubMed1999

Development of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis reference method for the analysis and identification of fish species in raw and heat-processed samples: a collaborative study.

A collaborative study was carried out in seven European labs with the aim of achieving a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) standard operation procedure to identify fish species in raw and cooked samples. Urea and SDS-containing solutions were evaluated as extractants. Several preelectrophoretic operations--such as treatment with RNase/DNase, ultrafiltration and desalting--and up to ten types of gels and three SDS-PAGE systems were considered. The SDS-containing solution allowed a higher protein extractability than urea. Unlike urea extraction, SDS extraction seemed not to be influenced so much by the state of the sample (raw, cooked at 60 degrees C, cooked at 85 degrees C). Desalting, ultrafiltration or treatment with RNase/DNase did not improve the discriminatory power of the protein patterns. Commercial homogeneous 15% ExcelGels, especially when they were silver stained, yielded good results and afforded higher reproducibility, thus allowing a better matching of results among the laboratories participating in this collaborative study. Under the optimized technical conditions described above, all the fish species tested, either raw and cooked, yielded reproducible and discriminant species-specific protein patterns.

Animals↗
PubMed1999

A standardized method of identification of raw and heat-processed fish by urea isoelectric focusing: a collaborative study.

A urea-isoelectric focusing (urea-IEF) method of identifying fish species in processed fishery products was investigated as an interlaboratory collaborative study. The technique was optimized with respect to (i) protein extraction conditions, composition of the extraction solution (urea and SDS solutions), determination of protein concentrations of the fish extracts (five tested methods); (ii) nature of gel (with carrier ampholytes and Immobilines), conditions of rehydration of commercial dry gels, urea concentration; (iii) staining conditions, Coomassie blue and silver staining. The results of various experiments were compared to select the most appropriate methodology, with respect to the discrimination power of differentiating species with the minimal influence of heat processing, reproducibility, speed, and ease of application. The method recommended meets the requirements of food control and customs laboratories.

Fish Products↗
PubMed1999

A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease.

Local inflammatory processes surrounding the amyloid plaques contribute to the progression and acceleration of the Alzheimer's disease (AD)-related neurodegeneration. Interleukin-6 (IL-6) is an inflammatory cytokine with possible involvement in the local immune response occurring in the central nervous system of AD patients. We tested the hypothesis as to whether a genetic polymorphism of the IL-6 gene (IL-6) modifies the age at onset and risk for sporadic AD. Our results support an association of the C allele of the IL-6 genotype with a delayed initial onset and reduced disease risk and indicate that genetically determined alterations of the immune response may modify the course of AD.

Age of Onset↗
PubMed1998

Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL.

Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A, CDKN2A, MDM2, MYC, RB1, REL, and TP53. The gene found to be altered most frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%) hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL without homozygous CDKN2A loss revealed methylation of the CpG island within exon 1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA expression was performed for 11 tumors and showed either no or weak signals. Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either completely negative or showed expression restricted to single tumor cells. None of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1 revealed no amplification, rearrangement or overexpression. The retinoblastoma protein was strongly expressed in all tumors. Only one PCNSL showed a mutation of the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG:Arg to Trp). No evidence of BCL2 gene rearrangement was found in 11 tumors investigated. The bcl-2 protein, however, was strongly expressed in most tumors. None of the 20 PCNSL demonstrated gene amplification of MDM2, MYC or REL. In summary, inactivation of CDKN2A by either homozygous deletion or DNA methylation represents an important molecular mechanism in PCNSL. Mutation of the TP53 gene and alterations of the other genes investigated appear to be of minor significance in these tumors.

Aged↗
PubMed1994

The Na-K-2Cl cotransporter is in a permanently activated state in cytoplasts from Ehrlich ascites tumor cells.

Brief incubation of Ehrlich ascites tumor cells with cytochalasin B causes the formation of blebs in the surface membrane. Gentle homogenization removes the blebs as intact cytoplasts which contain neither mitochondrian or nucleus, nor other cytoplasmic membranous organelles. The Na-K-2Cl cotransporter is present in the cytoplasts in a permanently activated state, whereas the Na-K-2Cl transport system in unperturbed intact cells is silent. Pretreatment of intact cells with cytochalasin B for 1 min stimulates the bumetanide-inhibitable K+ influx approximately fivefold. The influx into purified cytoplasts when expressed per g protein is three- to fourfold higher than the influx into cytochalasin B-treated intact cells. Thus, the membrane vesicles are enriched with the cotransporter, and the cotransporter is present in an activated state. The K influx into cytoplasts is inhibited about 40% by Na-free, Cl-free or bumetanide-containing media and to a similar extent by Fab fragments prepared from antiserum against purified proteins of the cotransporter. The KI for bumetanide was 0.19 +/- 0.06 microM for the cytoplasts as compared to 0.67 +/- 0.11 microM for the intact cells. SDS gel electrophoresis of membrane proteins from the cytoplast membranes compared to the membranes of intact cells shows a reduced number of bands and a majority of bands showing reduced staining, whereas a few bands are stained more intensely. Particularly notable is a band at approximately 80 kD, which is similar to the molecular weight previously reported for the main membrane protein isolated from intact cells using a bumetanide-Sepharose affinity column. An immunoblot of the cytoplast preparation using antibodies against the purified bumetanide binding proteins showed strong immunodetection of the approximately 80 kD protein.

Animals↗
PubMed1993

Na+, K+, Cl- cotransport and its regulation in Ehrlich ascites tumor cells. Ca2+/calmodulin and protein kinase C dependent pathways.

Net Cl- uptake as well as unidirectional 36Cl influx during regulatory volume increase (RVI) require external K+. Half-maximal rate of bumetanide-sensitive 36Cl uptake is attained at about 3.3 mM external K+. The bumetanide-sensitive K+ influx found during RVI is strongly dependent on both Na+ and Cl-. The bumetanide-sensitive unidirectional Na+ influx during RVI is dependent on K+ as well as on Cl-. The cotransporter activated during RVI in Ehrlich cells, therefore, seems to transport Na+, K+ and Cl-. In the presence of ouabain and Ba+ the stoichiometry of the bumetanide-sensitive net fluxes can be measured at 1.0 Na+, 0.8 K+, 2.0 Cl- or approximately 1:Na, 1:K, 2:Cl. Under these circumstances the K+ and Cl- flux ratios (influx/efflux) for the bumetanide-sensitive component were estimated at 1.34 +/- 0.08 and 1.82 +/- 0.15 which should be compared to the gradient for the Na+, K+, 2Cl- cotransport system at 1.75 +/- 0.24. Addition of sucrose to hypertonicity causes the Ehrlich cells to shrink with no signs of RVI, whereas shrinkage with hypertonic standard medium (all extracellular ion concentrations increased) results in a RVI response towards the original cell volume. Under both conditions a bumetanide-sensitive unidirectional K+ influx is activated. During hypotonic conditions a small bumetanide-sensitive K+ influx is observed, indicating that the cotransport system is already activated. The cotransport is activated 10-15 fold by bradykinin, an agonist which stimulates phospholipase C resulting in release of internal Ca2+ and activation of protein kinase C. The anti-calmodulin drug pimozide inhibits most of the bumetanide-sensitive K+ influx during RVI. The cotransporter can be activated by the phorbol ester TPA. These results indicate that the stimulation of the Na+, K+, Cl- cotransport involves both Ca2+/calmodulin and protein kinase C.

Animals↗
PubMed1993

Arterial pulse pressure and vasopressin release in humans during lower body negative pressure.

The hypothesis was tested that narrowing of arterial pulse pressure (PP) is a determinant of arginine vasopressin (AVP) release in humans. Six normal males completed a two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg, respectively, for 10 min each. None of these subjects experienced presyncopal symptoms. Arterial plasma AVP and plasma renin activity (PRA) (at 2-min intervals) only increased subsequent to a decrease in PP (invasive brachial arterial measurements) and stroke volume (ultrasound Doppler technique, n = 4). Simultaneously, mean arterial pressure did not change. A selective decrease in central venous pressure and left atrial diameter (echocardiography, n = 4) at LBNP of -20 mmHg did not affect AVP or PRA, whereas arterial plasma norepinephrine increased (n = 4). During LBNP, significant (P < 0.05) intraindividual linear correlations were observed between log(AVP) and PP in four of the subjects with r values from -0.75 to -0.99 and between log(PRA) and PP in all six subjects with r values from -0.89 to -0.98. In conclusion, these results are in compliance with the hypothesis that narrowing of PP in humans during central hypovolemia is a determinant of AVP and renin release.

Adult↗
PubMed1992

Activation of the Na+/K+/Cl- cotransport system by reorganization of the actin filaments in Ehrlich ascites tumor cells.

Reorganization (disassembly) of the actin filaments in Ehrlich ascites tumor cells, either by hypotonic treatment in the presence of Ca2+ or by addition of cytochalasin B, results in activation of the Na+/K+/Cl- cotransport system. However, other regulatory processes, some of which may be dependent on an intact filament system, are responsible for the activation of the Na+/K+/Cl- cotransport system after cell shrinkage.

Actins↗
PubMed1990

Inhibition of Na-K-C1 cotransport in Ehrlich ascites cells by antiserum against purified proteins of the cotransporter.

Two proteins were purified earlier from solubilized membranes of Ehrlich ascites cells by using a bumetanide-Sepharose affinity column. These proteins were proposed to be constituents of the Na-K-C1 cotransporter. However, the specificity of binding of bumetanide to the cotransporter was insufficient evidence for this proposal. We now have direct evidence that the purified protein contains components of the cotransporter. Antiserum raised against the bumetanide-binding proteins strongly inhibits Na-K-C1 cotransport measured by two independent methods. Cotransport was induced by hypertonic challenge and was measured as the bumetanide-sensitive portion of unidirectional C1 influx and as regulatory cell volume increase. In both assays, cotransport was strongly inhibited by the antiserum. Fab fragments of the antibodies inhibited cotransport to a similar extent.

Animals↗
PubMed1989

Isolation and reconstitution of furosemide-binding proteins from Ehrlich ascites tumor cells.

Furosemide-binding proteins were isolated from cholate-solubilized membranes of Ehrlich ascites tumor cells by affinity chromatography, using furosemide as ligand. Solubilized proteins retarded by the affinity material were eluted by furosemide. In reducing and denaturing gels, the major proteins eluted by furosemide were 100 and 45 kDa. In nonreducing, non-denaturing gels, homodimers of both polypeptides were found, whereas no oligomeric proteins containing both polypeptides were seen. It is concluded that the furosemide gel binds two distinct dimeric proteins. The isolated proteins were reconstituted into phospholipid vesicles and the K+ transport activity of these vesicles was assayed by measurement of 86Rb+ uptake against a large opposing K+ gradient. The reconstituted system was found to contain a K+ transporting protein, which is sensitive to Ba2+ like the K+ channel previously demonstrated to be activated in intact cells after cell swelling.

Animals↗
PubMed1988

Purification of proteins of the Na/Cl cotransporter from membranes of Ehrlich ascites cells using a bumetanide-sepharose affinity column.

Bumetanide-binding proteins were isolated from membranes of Ehrlich ascites tumor cells by affinity chromatography. An affinity column was constructed with the active moiety of bumetanide as a ligand using 4'-azidobumetanide, a photoactive analogue which inhibits Na/Cl cotransport in Ehrlich cells with high specificity. Covalent binding of the 4'-azidobumetanide with Sepharose was promoted by photolysis. Membranes isolated from Ehrlich cells were solubilized with n-octylglucoside. Solubilized proteins retarded by the affinity column were readily eluted by bumetanide. In reducing gels the major proteins eluted by bumetanide were approximately 76 kDa and 38-39 kDa. There were also two proteins of 32 to 35 kDa eluted in lesser amounts. No proteins retarded by the affinity column were eluted with extensive washing without bumetanide. Furthermore, bumetanide eluted no proteins from a "control" column lacking the specific ligand. Upon rechromatography with bumetanide in solution, bumetanide-eluted proteins were not retarded, but their purity was increased by the retardation of contaminating proteins. Bumetanide-binding protein purified in this manner were characterized further by electrophoresis in nonreducing, nondenaturing gels.

Animals↗
PubMed1988

Biomechanics of forward-reaching movements while sitting on fixed forward- or backward-inclining or tiltable seats.

Possible differences in spinal stress were evaluated during forward-reaching movements from chairs with, respectively, fixed backward-inclining, forward-inclining, and tiltable seat. Twenty-four healthy subjects, 12 female and 12 male, performed rhythmical sagittal movements with pins over a 40-cm distance. The posture in an upright and in a forward position was described by means of seven variables, measured by an inclinometer. Posture changes between these positions were then compared for the three types of chairs. No significant influence from the chairs on posture changes was observed. Thus, no variation in spinal stress can be anticipated during forward-reaching movements in any of the three types of chair. The discussion also presents a current status regarding tiltable and fixed forward-inclining seats.

Biomechanical Phenomena↗
PubMed1986

Identification of the anion exchange protein of Ehrlich cells: a kinetic analysis of the inhibitory effects of 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS) and labeling of membrane proteins with 3H-DIDS.

In Ehrlich ascites tumor cells 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid (DIDS) inhibits the chloride exchange both reversibly and irreversibly. The reversible inhibition is practically instantaneous and of a competitive nature with Ki about 2 microM at zero chloride concentration. This is succeeded by a slow irreversible binding of DIDS to the transporter, with a chloride dependence suggesting binding to the same site as for reversible DIDS binding/inhibition. To identify the membrane protein involved in anion exchange, cells were labeled with 3H-DIDS. Incubation of cells for 10 min with 25 microM DIDS at pH 8.2 leads to more than 95% inhibition of the DIDS-sensitive chloride exchange flux when the chloride concentration is low (15 mM). This condition was used for the 3H-DIDS-labeling experiments. After incubation the cells were disrupted, the membranes isolated and solubilized, and the proteins separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The distribution of the 3H-activity in the gel showed only one major peak, which could be related to protein with a mol wt of about 30,000 Daltons. The number of transport sites was estimated at about 400,000 per cell, and from the DIDS-sensitive chloride flux under steady-state conditions we calculate a turnover number of 340 ions per sec per site.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1986

Wrist support during typing--a controlled, electromyographic study.

The effects of wrist support on the trapezius and brachial extensor muscle loads during touch-typing were investigated with 12 secretaries, who were suffering pain in one or more of these muscles. They typed for 15 min at each of four experimental situations. The load on the trapezius was significantly greater with wrist support than without, and more marked the higher the support was adjusted. The radial extensor muscle load did not vary significantly. In spite of the higher trapezius load, most of the secretaries preferred a wrist support. Typing performance and body movements, estimated from the movements transferred to a tiltable chair-seat, were both unaffected by wrist support. Whether or not a wrist support should be used for typing cannot be concluded from the present investigation. However, it can be concluded that for touch-typing the keys should be positioned low - probably as low above the thighs as possible.

Journal Article↗
PubMed1985

Comparison of office chairs with fixed forwards or backwards inclining, or tiltable seats.

Three adjustments of an office chair seat: one inclining +10 degrees (forwards), one inclining -5 degrees (backwards), and one being freely tiltable from -8 degrees to +19.5 degrees were investigated using two groups of healthy female workers in a field (n = 12), and a laboratory study (n = 10), respectively. The seat adjustments were examined with regard to effects on foot swelling, lumbar muscular load, backrest pressure and subjective acceptability. Desk-work and typing were compared according to lumbar muscular activity, seat movements (tiltable seat), and backrest pressure. Foot swelling tended to increase with increasing seat height but was not influenced by the ability to tilt the seat or not. With the different seat adjustments lumbar muscular activity did not change systematically in spite of greater backrest pressure when the seat inclined backwards. The tiltable seat was preferred to the others. Typing was associated with a more constrained and tens posture than desk work, because movements, transferred to the tiltable seat, decreased and the muscular load increased. Backrest pressure was highest during typing. A tendency towards gradually increasing restlessness (i.e. seat movements) and increasing forward inclination of the tiltable seat with time was observed.

Adult↗