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Biomedical subjects

A Wallin

Publications and source records attributed to A Wallin.

At least 91 records · Page 5Linked to original sources
PubMed1995

Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.

Aged↗
PubMed1995

Studies on the effect of sulfite on benzo[a]pyrene-7,8-dihydrodiol activation to reactive intermediates in human polymorphonuclear leukocytes.

Sodium sulfite, a hydrolysis product of the environmental pollutant sulfur dioxide increased the activation of (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) to the (+)-anti-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) in phorbol myristate acetate (PMA)-stimulated human polymorphonuclear leukocytes (PMNs). This effect was potentiated in the presence of DMSO. No significant effect of sulfite on BP-7,8-diol activation was observed in resting leukocytes. As revealed by the 32P-postlabelling technique the dominant adduct in both intracellular DNA and to DNA added to the leukocytes was (+)-anti-BPDE bound to the exocyclic nitrogen of deoxyguanosine. The mechanism underlying the stimulatory effect of sulfite on diol epoxide production and increased DNA-binding probably involves one-electron oxidation of sulfite to a sulfur trioxide radical anion and subsequent reaction with molecular oxygen to form the corresponding peroxyl radical. This step obviously requires PMA-initiated oxidative burst and thus, production of superoxide radical anions (O2-.).

Biotransformation↗
PubMed1995

Evaluation of the liquid-chromatographic resolution of indenoindolic racemic compounds on three protein-based chiral stationary phases.

Three liquid-chromatography columns, containing immobilized proteins as chiral stationary phases (CSPs) were investigated for the direct separation of enantiomers of racemic indenoindolic compounds. By using an experimental design the effects of column temperature, pH, ionic strength, and type and concentration of organic solvent in the mobile phase on retention and resolution of racemic substances were systematically studied. The three CSPs investigated consisted of alpha(1)-acid glycoprotein (Chiral-AGP), bovine serum albumin (BSA-DSC) and ovomucoid (Ultron ES-OVM). The two enantiomers of all studied compounds could be separated on at least one of the three CSPs, which have different enantioselective properties.

Chromatography, Liquid↗
PubMed1995

Effects of hyperosmolar glucose, prostaglandin-F2 alpha and 15-methyl-prostaglandin-F2 alpha on human placental cells in vitro.

The objective of this study was to assess the ability of certain drugs, used for local injection therapy of ectopic pregnancy, to suppress the activities of cultured human placental cells. Placental cells from legal first trimester abortions were prepared by collagenase treatment and density gradient centrifugation. The cells were exposed to hyperosmolar glucose (500 mg/ml), 15-methyl-prostaglandin-F2 alpha (15-m-PGF2 alpha; 10(-7) to 10(-3) mol/l) and prostaglandin-F2 alpha (PGF2 alpha; 10(-5) to 5 x 10(-3) mol/l) for 30 min on days 2-4 after seeding. The effects on the secretion of human chorionic gonadotrophin (HCG) and progesterone, as well as on the protein content per culture well, were measured. Hyperosmolar glucose was the most effective drug and caused a marked decrease of the protein content in the culture wells and a reduction of progesterone secretion. Of the two prostaglandins, only 15-m-PGF2 alpha affected the viability of the cells and reduced the protein content of the wells. The clinical effectiveness of the two groups of drugs seems to be similar but certain in-vitro effects are different. Thus in vivo they may act on different target tissues. Against this background, the combination of hyperosmolar glucose and prostaglandins might be an interesting approach for local injection therapy for tubal pregnancy.

Carboprost↗
PubMed1995

Biochemical and morphological effects of contrast media on the kidney.

The intravenous use of roentgen contrast media (CM) is associated with a low incidence of renal impairment. This paper considers the intravascular handling and retention of CM in relation to effects on renal function - specifically the ability of the kidney to reabsorb and catabolise low molecular weight proteins. Renal morphology following experimental administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuoles or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation involving the uptake of CM appears to be analogous to dextran uptake that occurs via fluid phase endocytosis. These vacuoles or CM droplets are abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of (14)C iodixanol (3g I/kg) from the kidneys between 3.5 hours to 7 days after administration was about 1% of the dose, with some 0.2% of the original dose still present at 28 days. Subcellular analysis to determine the site of the radiolabel showed that the (14)C was associated with lysosomal marker enzymes. The CM-induced vacuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of (125)I-labelled cytochrome C with iodixanol showed some impairment of low molecular weight protein reabsorption, but remarkably this process was not effected when the vacuoles were fully formed. The conspicuous morphology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally significant impairment of tubular or cellular processes.

Animals↗
PubMed1994

Regulation of the hypothalamic-pituitary-adrenal axis in dementia disorders.

In 163 patients with dementia disorders, subdivided into Alzheimer's disease with early onset (AD; n = 40), senile dementia of the Alzheimer type (SDAT; n = 56), vascular dementia (VAD; n = 45) and dementia of unspecified type (NUD; n = 22) the dexamethasone suppression test (DST) was performed. The patients were rated according to the DSM-III-R criteria as having mild, moderate or severe dementia and were also assessed using the GBS scale which gives a profile of the dementia syndrome. In the total group of dementia there were significant correlations between severity of dementia and post-DST levels. The frequency of pathological DST also correlated significantly with the severity of dementia. In the subgroups of dementia a strong correlation between severity of dementia and high post-DST cortisol levels was found only in the VAD group. Between the subgroups of dementia disorders there were no significant differences in basal cortisol levels. The percentage of pathological DST was lowest in the AD group (40%). It was somewhat higher in the VAD group (49%), still higher in the SDAT group (54%) and highest in the NUD group (59%). When the relationship between post-DST cortisol levels and GBS scores was analyzed, significant correlations were found mainly in the VAD group. There intellectual impairment, anxiety, fear-panic and restlessness correlated significantly with post-DST cortisol levels. The results indicate hypothalamic overactivity in a substantial number of demented patients. In VAD and to a certain extent also in SDAT a disconnection between cortical areas, including the hippocampus, and the hypothalamus is assumed. Overactivity in the hypothalamic-pituitary-adrenal (HPA) axis is due to stress, and an insufficient feedback system leads to chronic stress adaptation failure.

Aged↗
PubMed1994

Nitrite-stimulated DNA-binding of carcinogenic diol epoxides from benzo[a]pyrene-7,8-dihydrodiol in human polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMNs) previously treated with 12-O-tetradecanoyl phorbolmyristate-13-acetate (PMA) to initiate the oxidative burst activate (-)-trans-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene [(-)-BP-7,8-diol)] to DNA-binding intermediates. The 32P-postlabelling technique and HPLC-analysis of enzyme-digested DNA were employed for identification of DNA-adducts following incubation of (-)-BP-7,8-diol in PMNs. The results are consistent with the formation of (+)-anti-BPDE, the ultimate carcinogen of BP, bound via trans-addition of the C-10 position in the diol epoxide molecule to the exocyclic nitrogen of deoxyguanosine (BPDE-N2-dG adduct). Addition of nitrite, the major aqueous dissolution product of NO2, stimulated the formation of (+)-anti-BPDE and subsequent binding to both nuclear DNA in PMNs (about twofold) and to DNA present outside the cells (two- to fourfold). Preliminary experiments suggest that nitrite stimulates the metabolism of (-)-BP-7,8-diol by direct interaction with myeloperoxidase and hydrogen peroxide. Consistent with previous work by us and others, the covalent binding of (+)-anti-BDPE to extracellular targets demonstrate that these reactive products, expected to be formed intracellularly, can be released from the leukocytes. Measurement of hydroxyl radical-induced DNA damage by estimating the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in resting PMNs revealed low amounts of adducts (1 adduct/10(6) dG-1 adduct/10(5) dG). Pretreating the cells with PMA or PMA in conjunction with nitrite had no significant effect on 8-OH-dG adduct formation.

Biotransformation↗
PubMed1994

Neuron specific enolase in cerebrospinal fluid: a biochemical marker for neuronal degeneration in dementia disorders?

Alzheimer's disease (AD) is the most common disease causing dementia. Today the clinical diagnosis of AD is made by way of exclusion, and no biochemical markers are available to assist the clinical diagnosis. We examined the potential of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) as a diagnostic marker for AD. NSE was determined with a monoclonal antibody two-site immunoradiometric assay (IRMA) in serum (S) and cerebrospinal fluid (CSF) samples from 45 patients with "probable Alzheimer's disease (AD)", 19 patients with vascular dementia (VAD) and 33 age-matched healthy individuals. There was no significant correlation between S-NSE and CSF-NSE, or between CSF/S albumin ratio and CSF-NSE, findings suggesting that the major portion of CSF-NSE is intrathecally produced and that analysis of CSF-NSE alone (without accompanying analysis of serum) is sufficient. CSF-NSE was significantly higher in the AD group (4.7 +/- 2.7 ng/mL; p < 0.0001) and in VAD group (4.5 +/- 2.5 ng/mL; p < 0.001) as compared with the control group (2.2 +/- 1.0 ng/mL), while it did not differ significantly between the AD and the VAD group. These findings suggest that CSF-NSE have a potential as a non-disease specific marker for the neuronal degeneration in dementia disorders.

Aged↗
PubMed1994

Comorbidity of other chronic age-dependent diseases in dementia.

This study compares the prevalence rates of 5 common age-dependent diseases in non-demented and demented subjects. Control and dementia populations were approximately age-matched and their numbers also approximated. Prevalence rates for hypertension, myocardial infarction (MI), stroke, cancer and diabetes were determined. The rates of two or more coexisting diseases in the same patient were also compared. Two populations were studied: one was designated the autopsy series, and the other the hospital series. In the autopsy series, the rate of cardiomegaly/hypertension was 1.3 times higher in the control than in the dementia population, and for MI it was 1.7 times higher in the former than in the latter. The rate for stroke was higher in the control group by only a factor of 1.1, for cancer by only a factor of 1.2, and for diabetes the rates were almost identical in the two populations. The rate differences were statistically significant only with respect to cardiomegaly and MI. When the non-vascular and vascular dementias were compared, the rates in the latter were higher by only a factor of 1.3 for cardiomegaly, stroke, cancer and diabetes; for MIs, the rates were about the same in the two dementia categories. The data for two or more coexisting diseases were almost identical in control and dementia autopsy populations. In the hospital series, the hypertension rate was 1.6 times higher in the control than in the Alzheimer's disease (AD) group; for MI, the control group was higher by a factor of 1.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.

There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Quantitative MR imaging of lumbar intervertebral disc and vertebral bodies: methodology, reproducibility, and preliminary results.

Since relaxation times are influenced by the hydration of the tissue and the chemical environment of the water molecules, T1 and T2 measurements (quantitative MRI) could be used as an indicator for the water content and the biochemical composition of lumbar intervertebral discs. The discriminating power of quantitative MRI for tissue characterization in individuals (for clinical diagnosis) and in cohorts (e.g. for investigations on disc physiology or composition) relies on the reproducibility in relation to the expected tissue differences. We therefore investigated the reproducibility in vitro (lumbar spine phantom) and in vivo (10 volunteers). To estimate the differences between normal and pathologic tissues in vivo, 100 normal and 20 herniated intervertebral discs were examined by quantitative MRI in a first application of our method. The relaxation times were calculated from a set of 20 images obtained with five single-slice/multi-echo sequences at different TR values on a commercial whole-body system (1.5 T). We have found a satisfactory reproducibility in vitro (T1: 1.9%; T2: 6.2%), while the reproducibility was less satisfactory in vivo (T1: 16.4%; T2: 13.4%). Calculated from theses values, differences in relaxation times of various tissues must exceed 486 ms for T1 and 24 ms for T2 (tolerance limits) to allow discrimination with a 95% confidence in individuals. We observed statistically significant (p = 0.001) mean differences between normal (n = 100) and herniated (n = 20) intervertebral discs (delta T1: 196 ms; delta T2: 15 ms). Although statistical significant in cohorts, a discrimination of normal and herniated intervertebral discs is limited by quantitative MRI in individuals, since the differences are smaller than the tolerance limits necessary for a reliable clinical diagnosis. However, our results indicate that variations in the disc hydration and/or composition can be noninvasively detected by quantitative MRI in studies of cohorts with sufficient accuracy.

Adolescent↗
PubMed1994

Ubiquitin in cerebrospinal fluid in Alzheimer's disease and vascular dementia.

Ubiquitin (Ub) was determined by a competitive enzyme-linked immunosorbent assay (ELISA) in serum (S) and cerebrospinal fluid (CSF) samples from 29 patients with 'probable Alzheimer's disease' (AD), 14 patients with vascular dementia (VAD), and 13 healthy individuals. The mean concentration of Ub in CSF (110 +/- 20 ng/mL) was about 20% of that in serum (940 +/- 120 ng/mL) in healthy controls. There was no significant correlation between S-Ub and CSF-Ub, or between the CSF/S.Ub ratio and the CSF/S albumin ratio. These findings suggest that a major portion of CSF-Ub is intrathecally produced. CSF-Ub was increased while S-Ub was decreased in both AD and VAD patients as compared with controls. As a consequence, the CSF/S Ub ratio showed good discrimination between patients and controls: 22/29 (76%) of the AD patients and 9/14 (64%) of the VAD patients had a CSF/S Ub ratio that was higher than the highest control value. No significant differences in any of the parameters were found between AD and VAD. Ub is involved in an ATP-dependent proteolytic pathway and also acts as a heatshock protein. The increase in CSF-Ub in AD and VAD may therefore be interpreted as a cytoprotective response to abnormal or damaged proteins, and CSF-Ub may have a potential as a non-disease-specific marker for cerebral degeneration.

Aged↗
PubMed1994

Altered blood-brain-barrier function in Alzheimer's disease?

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common causes of dementia. As yet, no definitive biological antemortem marker has been established for differential diagnosis of AD or VD. In this study, proteins of cerebrospinal fluid (CSF) from AD, VD and control patients were analyzed by two-dimensional (2-D) electrophoresis with immobilized pH gradients in the first dimension. No specific changes for AD or VD could be detected in the 2-D CSF patterns. However, a spot of haptoglobin alpha-1 chains (13.5 kDa; approximate pI 4.6) was found to be present in the majority of 2-D CSF maps from the dementia cases, suggesting a high-molecular-weight transudate type of alteration in the blood-brain barrier with considerable frequency in AD.

Aged↗
PubMed1994

Individual, culture-specific alterations in the human endothelial glutathione system: relationships to oxidant toxicity.

In this communication we report on the effects of serial passage of human umbilical vein endothelial cells on the levels of GSH and activities of selenium-dependent GSH peroxidase (SeGSHpx) and GSSG reductase (GSSGred) in confluent monolayers of human umbilical vein endothelial cells derived from 4 individual donors. The mean levels of GSH in confluent monolayers of individual human umbilical vein endothelial cells batches fell from an average of 35 nmol/mg protein to 16 nmol/mg protein from primary culture to the third passage, with little interindividual variation noted. Simultaneously, the mean activities of SeGSHpx and GSSGred remained unaltered during serial culture, again with little interindividual variation noted. However, serial passage of the cells from different individuals did not affect the sensitivity of the cells to sublethal injury induced by H2O2 (10 or 100 microM), as judged by the stimulated release of (3H)-deoxyglucose. When these GSH-dependent parameters were assayed during the coarse of the growth of an individual passage of cells, GSH levels declined following trypsinisation, but the activities of SeGSHpx and GSSGred remained essentially unaltered, when the data were standardised to cell number. On the other hand, standardisation of these data to cell protein revealed decreases in all three parameters following trypsinisation, indicating the introduction of artefacts into the data and the unsuitability of this standardisation procedure. For the first four hours following plating, all of the GSH-dependent parameters remained essentially unaltered, but began increasing thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1994

Hypothalamic dysfunction in dementia.

In 40 patients with Alzheimer's disease (AD) 56 patients with senile dementia of Alzheimer type (SDAT) and 45 patients with vascular dementia (VAD) degree of dementia was rated into mild, moderate and severe according to DSM-III-R and on the GBS scale. Basal cortisol levels were determined and a dexamethasone test (DST) performed. Basal cortisol levels were high in all the dementia groups. Forty percent of AD patients, 54% of SDAT patients and 49% of VAD patients were non suppressors. Significant correlations between post DST cortisol levels and rated variables were seen mainly in the VAD group. The pathological DST could hardly be explained by presence of depression. In dementia, especially those with white matter disturbances, disconnections between cortical areas (hippocampus) and hypothalamus can be assumed explaining a reduced inhibitory tone on hypothalamus. When characterizing VAD patients with pathological DST these patients were significantly more intellectually impaired, showed higher degree of anxiety, restlessness and fear-panic than VAD patients with normal DST. Some behaviourial disturbances in dementia disorders may be a consequence of HPA over activity rather than a consequence of the dementia process itself.

Aged↗