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S Daniel

Publications and source records attributed to S Daniel.

At least 55 records · Page 3Linked to original sources
PubMed1997

Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease.

Depletion of reduced glutathione occurs in the substantia nigra in Parkinson's disease and in incidental Lewy body disease (presymptomatic Parkinson's disease) which may implicate oxidative stress in the neurodegenerative process. In this study mercury orange fluorescent staining and immunostaining with an antibody to reduced glutathione have been used to determine the distribution of reduced glutathione in the substantia nigra in Parkinson's disease compared with normal individuals. Mercury orange staining showed moderate background levels of fluorescence in the neuropil in both control and Parkinson's disease substantia nigra and localised reduced glutathione to the somata of melanized nigral neurons and glial elements of the neuropil. Neuronal nuclei revealed a relative lack of fluorescence after mercury orange staining. There was a significant depletion of reduced glutathione in surviving neurons in Parkinson's disease compared to nerve cell populations in control tissue. Mercury orange fluorescence indicated a high concentration of reduced glutathione in a subpopulation of non-neuronal cells, most likely astrocytes or microglia. Immunohistochemical examination of nigral tissue from the same Parkinson's disease and control patients with an antibody to glutathione showed staining in neuronal perikarya and axonodendritic processes of melanized nigral neurons which was generally most intense in control neurons. Moderately intense staining of the background neuropil, most prominent in control nigras, and staining of capillary walls was also detected. Intense staining was seen in cells with the morphological features of glial cells in both control and PD nigra. These data show a significant presence of reduced glutathione in the cell bodies and axons of nigral neurons. They are in agreement with biochemical studies showing depletion of reduced glutathione in substantia nigra in Parkinson's disease, and indicate a significant loss of neuronal reduced glutathione in surviving nigral neurons in Parkinson's disease.

Aged↗
PubMed1997

Discrimination of Alzheimer's disease and normal aging by EEG data.

Quantitative EEG results in Alzheimer's disease may be summarized by the term 'slowing', i.e. slow frequencies (delta, theta) are increased and fast frequencies (alpha, beta) are decreased. But how can EEG data be used to discriminate AD patients from controls by means of EEG data? Discriminant analysis may produce false predictions using too many predictors, as is often the case in EEG studies. We studied 4 approaches to this problem: Classification by group means, stepwise discriminant analysis, a neuronal network using back propagation and discriminant analysis preceded by principal components analysis (PCA). A maximum of 86.6% correct classifications was reached using the last mentioned approach with EEG data alone. Including age as a moderator variable in a subgroup, 95.9% correct classifications were reached.

Aged↗
PubMed1997

Induction of tumor necrosis factor alpha in human neuronal cells by extracellular human T-cell lymphotropic virus type 1 Tax.

To examine the role of human T-lymphotropic virus type 1 (HTLV-1) Tax1 in the development of neurological disease, we studied the effects of extracellular Tax1 on gene expression in NT2-N cells, postmitotic cells that share morphologic, phenotypic, and functional features with mature human primary neurons. Treatment with soluble HTLV-1 Tax1 resulted in the induction of tumor necrosis factor alpha (TNF-alpha) gene expression, as detected by reverse-transcribed PCR and by enzyme-linked immunosorbent assay. TNF-alpha induction was completely blocked by clearance with anti-Tax1 monoclonal antibodies. Furthermore, cells treated with either a mock bacterial extract or with lipopolysaccharide produced no detectable TNF-alpha. Synthesis of TNF-alpha in response to soluble Tax1 occurred in a dose-dependent fashion between 0.25 and 75 nM and peaked within 6 h of treatment. Interestingly, culturing NT2-N cells in the presence of soluble Tax1 for as little as 5 min was sufficient to result in TNF-alpha production, indicating that the induction of TNF-alpha in NT2-N does not require Tax1 to be continually present in the culture medium. Treatment of the undifferentiated parental embryonal carcinoma cell line NT2 with soluble Tax1 did not result in TNF-alpha synthesis, suggesting that differentiation-dependent, neuron-specific factors may be required. These results provide the first experimental evidence that neuronal cells are sensitive to HTLV-1 Tax1 as an extracellular cytokine, with a potential role in the pathology of HTLV-1-associated/tropical spastic paraparesis.

Cell Differentiation↗
PubMed1997

[Degree of disability of demented patients as judged by relatives and experts (disability insurance)].

Health insurance companies commission medical expert opinions rating the severity of clinical improvement in order to provide adequate nursing support. We compared these ratings on 28 demented patients with the ratings from carers and with our own examination. The results indicate that the expert opinions underestimated the severity of improvement and adequate support in some of the cases. We discuss whether these discrepancies may be due to the peculiarities of dementia.

Aged↗
PubMed1996

Regulation of acetyl coenzyme-A carboxylase gene in a transgenic animal model.

The gene for acetyl-CoA carboxylase, the rate-limiting enzyme in the biosynthesis of long-chain fatty acids, contains two promoters; promoter I (PI) and promoter II (PII) which are responsible for generation of class I and class II ACC mRNAs, respectively. Class I ACC mRNAs are present in adipose tissue, but only a trace was found in the liver under normal physiological conditions. However, class I mRNAs were induced under stimulated lipogenic conditions. To investigate how PI is regulated in vivo, we generated transgenic mice containing a reporter gene under the control of PI. In transgenic mice, PI is generally inactive and a small amount of PI activity was found only in the adipose tissues of female animals. Stimulated lipogenic conditions activated PI about 17-fold over normal conditions and again only in white adipose tissues of female animals.

Acetyl-CoA Carboxylase↗
PubMed1996

The GTP-cyclohydrolase I gene in atypical parkinsonian patients: a clinico-genetic study.

GTP cyclohydrolase I (GTPCH) has recently been identified as the first causative gene for Dopa-responsive dystonia (DRD). DRD typically presents with dystonia in the lower limbs in childhood, but may produce an akinetic-rigid syndrome in middle and old age. We have sequenced the GTPCH gene in 29 Parkinsonian patients without a positive family history for DRD, but who shared at least one feature of the akinetic-rigid presentation of DRD: 23 patients had at least one living relative who also suffered from an akinetic-rigid syndrome; 2 patients had an abnormally mild course of their parkinsonism which was extremely dopa-responsive. DNA was also analysed from 4 brain samples of patients who were clinically diagnosed as suffering from Parkinson's disease, but then did not show any pathological findings at post mortem. No changes in the sequence of the GTPCH gene were detected. We conclude that so far there is no evidence that mutations of the GTPCH gene are responsible for the development of parkinsonism in patients without a positive family history of DRD.

Aged↗
PubMed1996

Dephosphorylation of Sp1 by protein phosphatase 1 is involved in the glucose-mediated activation of the acetyl-CoA carboxylase gene.

When mouse 30A5 preadipocytes are exposed to high glucose concentrations, acetyl-CoA carboxylase is induced through glucose activation of promoter II of the acetyl-CoA carboxylase gene. Glucose treatment of the cells increases Sp1 binding to two GC-rich glucose response elements in promoter II. We have investigated the mechanism by which glucose increases Sp1 binding and transactivation of promoter II in 30A5 cells. DNA mobility shift assays have shown that nuclear extracts from glucose-treated cells exhibit increased Sp1 binding activity. This increase in the binding activity is not due to glucose-mediated changes in the amount of Sp1 in the nucleus but to an increase in the activity that modifies Sp1 so that it binds more effectively to the promoter sequence. This Sp1 modifying activity is inhibited by okadaic acid and phosphatase inhibitor 2, and has a molecular mass of 38-42 kDa. The catalytic subunit of type 1 protein phosphatase, whose molecular mass is 38 kDa, also increased the ability of Sp1 to bind to promoter II. Treatment of nuclear extract with antibodies against the catalytic subunit partially suppressed the nuclear activity for Sp1 activation. From these results, we conclude that the Sp1 transcription factor exhibits enhanced binding to promoter II and transcriptional activation is the result of glucose-induced dephosphorylation by type 1 phosphatase.

Acetyl-CoA Carboxylase↗
PubMed1996

Identification of a second human acetyl-CoA carboxylase gene.

Acetyl-CoA carboxylase (ACC), an important enzyme in fatty acid biosynthesis and a regulator of fatty acid oxidation, is present in at least two isoenzymic forms in rat and human tissues. Previous work has established the existence of a 265,000 Da enzyme in both the rat and human (RACC265; HACC265) and a higher-molecular-mass species (275,000-280,000 Da) in the same species (RACC280; HACC275). An HACC265 gene has previously been localized to chromosome 17. In the present study, we report cloning of a partial-length human cDNA sequence which appears to correspond to HACC275 and its rat homologue, RACC280, as judged by mRNA tissue distribution and cell-specific regulation of mRNA/protein expression. The gene encoding this isoenzymic form of ACC has been localized to the long arm of human chromosome 12. Thus, ACC is represented in a multigene family in both rodents and humans. The newly discovered human gene and its rat homologue appear to be under different regulatory control to the HACC265 gene, as judged by tissue-specific expression in vivo and by independent modulation in cultured cells in vitro.

Acetyl-CoA Carboxylase↗
PubMed1996

Sp1 mediates glucose activation of the acetyl-CoA carboxylase promoter.

Acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in the biosynthesis of fatty acids, is induced in the presence of high glucose levels. The ACC gene contains two promoters: promoter I (PI) expression is inducible under lipogenic conditions, while promoter II (PII) expression, even though constitutively expressed in all tissues, is also controlled under various physiological conditions. Examination of the expression pattern of a series of deletion constructs of PII showed that the region from -340 to -249 was essential for ACC induction. In addition, by electrophoretic mobility shift assays, supershift assays, and DNase I footprinting studies, we have detected the binding of the transcription factor Sp1 at the two GC-rich sequences located within the -340 to -249 region of promoter II. Mutations at the GC-rich sequences prevented binding of Sp1, and the induction of the PII promoter was no longer observed. Cotransfection studies, in Drosophila Schneider SL2 cells, with the Sp1 expression vector and PII-CAT constructs, have further confirmed the activation of promoter II by Sp1. In addition, we have identified Sp3, another member of the Sp1 family of transcription factors, as a second factor that can bind to the glucose response elements of PII.

Acetyl-CoA Carboxylase↗
PubMed1996

Quantitative EEG in frontal lobe dementia.

A study on quantitative EEG in 14 patients with frontal lobe dementia (FLD), 14 patients with Alzheimer's disease (AD), and 14 healthy controls was conducted using a complete set of EEG parameters: band power, coherence and fractal dimension. Contrary to earlier studies, we observed higher theta power and sagittal interactions in higher frequency bands in the FLD than in the control group. Lateral interactions of coherence and two indices of fractal dimension were lower in FLD than in controls. There was greater electrophysiological resemblance between the control group and FLD than between any of these groups and AD. This was documented by the results of a discriminant analysis which led to a correct overall classification of 66% of the subjects with misclassifications occurring primarily between control and FLD group.

Analysis of Variance↗
PubMed1996

[Alzheimer dementia and normal aging. Clinical, neuroradiologic, neurophysiologic and molecular biology follow-up data].

A total of 30 patients with clinically diagnosed Alzheimer's disease and 55 healthy, age-approximated controls were followed up over a 2-year period to compare the course of functional and cognitive impairment, quantitative morphological and functional brain changes. No remarkable changes were observed within the control group in any of these modalities. There were significant differences between patients and controls at the first examination: Mini-Mental State Examination (MMSE), 16.1 +/- 7.3 compared with 28.7 +/- 1.4; left lateral ventricle 2.7 +/- 1.1% versus 1.6 +/- 0.7% of the total intracranial volume; right lateral ventricle 2.7 +/- 1.4% versus 1.4 +/- 0.4%; absolute delta-power 1.1 +/- 0.3 versus 0.9 +/- 0.2 microV2; and absolute theta-power 1.1 +/- 0.3 versus 0.8 +/- 0.2 microV2 (means +/- standard deviation). In the patient group, scores on the Blessed dementia rating scale deteriorated from 10.6 +/- 6.1 to 17.9 +/- 9.6; the MMSE decreased by 8.0 +/- 3.7; the left lateral ventricle volume increased by 0.9 +/- 0.7%, the right by 0.9 +/- 0.7% of the total intracranial volume; absolute delta-power increased by 0.2 +/- 0.4 microV2 and theta-power by 0.1 +/- 0.3 microV2. We could not confirm a relationship between age, age at onset or apolipoprotein E4 gene dose and the rate of clinical change. High initial Blessed dementia scores were correlated with more severe ventricular enlargement, and delta-theta increase during the follow-up period. High initial theta-power predicted more severe functional and cognitive deterioration. To our knowledge, this is the first longitudinal study reporting quantitative clinical, morphological and EEG-changes measured in two points in time in patients and non-demented controls.

Aged↗
PubMed1996

Sixteen weeks of hexarelin therapy in aged dogs: effects on the somatotropic axis, muscle morphology, and bone metabolism.

Hexarelin (HEXA; 500 micrograms/kg/die, s.c.) was administered for 16 weeks to six old beagle dogs. The treatment consisted of three on-drug periods spaced by two off-drug periods. During each on period, the growth hormone (GH) peak response to HEXA initially increased and then dropped to pretreatment values. Each time, a wash-out interval restored the same pattern of GH responsiveness. HEXA significantly augmented the indices of spontaneous pulsatility of GH, but plasma insulin-like growth factor I levels did not change during treatment. HEXA apparently reduced bone resorption since it significantly decreased the urinary concentration of lysylpyridinoline, a bone matrix component. Bone formation apparently was not affected since unchanged levels of alkaline phosphatase were recorded. In three of six old dogs, HEXA induced an improvement of some morphological and biochemical muscular indices, evaluated in muscle specimens that, instead, remained unchanged in a group of young untreated controls. These findings indicate that HEXA effectively releases GH and primes the pituitary of old dogs, and strengthen the view that in aging, GH secretion may be restored by pharmacological means. It would also appear that HEXA-induced GH release improves some indices of body composition in old dogs.

Animals↗
PubMed1996

First-time suicide attempters, repeat attempters, and previous attempters on an adolescent inpatient psychiatry unit.

OBJECTIVE: To compare clinical characteristics of hospitalized adolescents who (1) have recently made their first suicide attempt, (2) have recently made a second or subsequent attempt, (3) have made previous but no recent attempts, or (4) have never made an attempt. METHOD: Semistructured psychiatric diagnostic interviews were used to determine history of recent and previous suicidal behavior among 225 consecutively admitted adolescents to an inpatient psychiatric facility. Twenty-seven first-time attempters, 32 repeat attempters, and 40 previously suicidal youths were compared with 126 nonsuicidal youths in terms of severity of self-reported depressive symptoms, state anxiety, trait anxiety, state anger, and trait anger. RESULTS: Repeat attempters and previous attempters both reported more depressive symptomatology and trait anxiety than did nonsuicidal youths. In addition, youths with a previous history of suicide attempts, but no recent attempts, evidenced more trait anger than all other groups. First-time suicide attempters reported levels of distress that were intermediate to the other groups. CONCLUSIONS: Repeat attempters and previous attempters in hospital settings both report more distress than do nonsuicidal youths. Interventions should focus not only on resolution of immediate crises, but also on youths' ability to cope with ongoing difficulties that engender depression and chronic anxiety.

Adaptation, Psychological↗
PubMed1996

Linkage disequilibrium between HLA class II (DR, DQ, DP) and antigen processing (LMP, TAP, DM) genes of the major histocompatibility complex.

TAP, LMP and DM genes map within the major histocompatibility complex (MHC) class II region between the DQB1 and DPB1 loci, and are involved in the processing of peptides bound to HLA class I or class II molecules. In order to determine the various linkage disequilibria existing between these genes and HLA class II genes, we have analyzed TAP1, TAP2, LMP2, DMA, DMB, DRB1, DQA1, DQB1 and DPB1 polymorphisms in 162 unrelated healthy Caucasian individuals. Many positive or negative associations were observed between alleles at these loci, such as between DR/DQ and TAP2, DM or LMP, between DP and DMB, and between TAP2 and DM, TAP2 and LMP. Conversely, no linkage disequilibrium was detected between some closely related genes (DR/DQ and TAP1, TAP1 and TAP2, LMP2 and DM), in agreement with the existence of recombination hot spots in this region. Other weak linkage disequilibria are likely to exist in this region. These data allow to define some conserved MHC class II haplotypes including HLA class II and TAP, LMP and DM alleles. Furthermore, the knowledge of such linkage disequilibria is of outstanding importance in order to avoid misinterpretation of the data when studying MHC class II associations with autoimmune diseases.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Review on the multifactorial aspects of bioincompatibility in CPB.

Over the last few years, a great emphasis has been placed on the bioincompatibility of foreign, nonphysiological materials used during CPB. It is only recently that bioincompatibility has objectively been recognized to be multifactorial, with the dominant implicated sources being cardiotomy blood suction, shear stresses or flow dynamics and, to a lesser degree, the blood/artificial surface interactions, the heparin/protamine complex and the various forms of emboli or debris. In summary, in CPB, the reduction of postoperative complications, such as whole body inflammatory reactions, bleeding and organ dysfunctions, can only be impacted if the primary, dominant sources of bioincompatibility are reduced or eliminated.

Biocompatible Materials↗
PubMed1996

Longitudinal cognitive, electroencephalographic and morphological brain changes in ageing and Alzheimer's disease.

BACKGROUND: The natural course of cognitive performance, electrophysiological alterations and brain atrophy in ageing and Alzheimer's disease (AD) has been investigated in numerous studies, but only few attempts have been made to examine the relationship between clinical, electroencephalographic (EEG) and morphological changes with quantitative methods prospectively over longer periods of time. METHOD: Fifty-five patients with clinically diagnosed AD and 66 healthy elderly controls were examined biannually using a cognitive test (CAMCOG), EEG band power and volumetric estimates of brain atrophy. RESULTS: On average cognitive performance deteriorated by 28 points on the CAMCOG in the AD group, the alpha/theta ratio decreased by 0.2, and the proportion of intracranial cerebrospinal fluid volume increased by 3.5% during a 2-year period. Similar changes were observed after a second 2-year interval. A multiple regression model demonstrated a significant influence of age on cognition and atrophy and a significant influence of the estimated duration of symptoms on cognition, alpha/theta ratio and brain atrophy at the initial examination. Cognitive performance at the first examination exerted significant effects on the performance and also on brain atrophy at re-examination after 2 or 4 years, whereas the EEG and neuroimaging findings at the previous examination were exclusively related to the corresponding findings at the follow-up examinations. In the control group no significant cognitive, EEG and morphological changes were observed after 2 and 4 years. CONCLUSION: After 2 consecutive follow-up periods, we were able to verify significant deteriorations of cognition accompanied by neurophysiological and neuroradiological changes in AD, but not in normal ageing. In clinically diagnosed AD, cognitive performance at the followup examination could not be predicted by the previous alpha/theta ratio or by the previous degree of global brain atrophy, whereas the cognitive test score determined not only performance, but also structural findings at follow-up. Performance on cognitive tests appears to be a more sensitive indicator of the degenerative process than EEG band-power and morphological changes in manifest AD. Neuroimaging, neurophysiology and genetic risk markers may be more important for the early differential diagnosis than for the prediction of the course of illness.

Age of Onset↗
PubMed1995

CD66b, CD66c and carcinoembryonic antigen (CEA) are independently regulated markers in sera of tumor patients.

Non-specific cross-reacting antigens (NCA-95 = CD66b and NCA-50/90 = CD66c) are members of the CEA (carcinoembryonic antigen = CD66e) family. Analysis of mRNA levels of CD66c in colon tumors suggests that this antigen is strongly up-regulated compared to its normal counterpart and could, therefore, be of clinical interest. CD66c is also expressed in normal lung and spleen tissues and, above all, on granulocytes. The appearance of CD66b in serum, the only strictly granulocyte-specific antigen, could point to the involvement of granulocytes in disease. Specific sandwich ELISAs have been established to determine CEA, CD66b and CD66c levels in serum. Controls have been carried out by testing sera from patients with benign tumors or inflammatory diseases and from healthy individuals. In sera of most patients suffering from solid tumors, sensitivities for CD66c are comparable to or lower than those for CEA. CD66c showed a much higher sensitivity in early colon tumor stages. Sensitivities over 40% have been determined for CD66b in sera of patients with uterine and kidney carcinomas. CML patients revealed sensitivities of 84% for CD66c and 47% for CD66b. Investigations of sera from patients with inflammatory colon diseases which are negative for CEA showed high sensitivity for CD66c but not for the granulocyte-specific CD66b. Patients with mastopathy revealed sensitivities of over 40% for both CD66c and CD66b. CD66b, CD66c and CEA are independently regulated proteins in a high percentage of patients. The simultaneous determination of CEA and CD66b/c can increase the sensitivities for malignant tumors but high sensitivities of CD66b/c for benign diseases limit their usefulness as tumor markers. CD66b may be interesting as a marker for kidney and corpus carcinomas, for which good markers are not yet available.

Adult↗