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J Pantel

Publications and source records attributed to J Pantel.

53 records · Page 3Linked to original sources
PubMed1997

Free luteinizing-hormone beta-subunit in normal subjects and patients with pituitary adenomas.

Most clinically nonfunctioning pituitary adenomas (NFPA) are found to be gonadotropinomas when assessed by immunocytochemistry. However, they are rarely associated with increased basal plasma levels of FSH, LH and/or alpha-subunit. It has been claimed that the paradoxical free LHbeta response to TRH may be a useful clinical tool for determining the gonadotropic nature of NFPA. We used a very specific and sensitive immunoradiometric assay (IRMA) for free LHbeta measurement and another specific IRMA to check the absence of free CGbeta, to study normal subjects and 26 patients with NFPA. Basal plasma levels of LHbeta were undetectable in normal men and premenopausal women in the early follicular phase. In contrast, normal postmenopausal women had increased basal plasma LHbeta, parallel to dimeric LH and alpha-subunit levels. In healthy subjects, stimulation with GnRH elicited an increase in LHbeta while TRH was ineffective. In patients with NFPA, LHbeta hypersecretion was found basally and/or after stimulation with TRH in 3 of 16 men, 3 of 5 premenopausal women, and 1 of 5 postmenopausal women, i.e. 7 of 26 patients (26%). In 3 of these 7 cases, alpha-subunit and/or FSH levels were also increased. The LHbeta measurement was thus truly informative on the gonadotropic nature of NFPA in only 4 out of 26 cases (15%). In addition, increased LHbeta levels and/or a positive response of free LHbeta to TRH was observed in 3 patients with pure prolactinomas but in no patients with GH-secreting adenomas. Thus, using this very sensitive and specific IRMA, free LHbeta measurement is rarely helpful for determining the gonadotropic nature of NFPA.

Acromegaly↗
PubMed1996

Mapping of HCG-receptor complexes.

Molecular forms of the porcine LH/CG receptor (pLHR) and complexes between hCG and either the full-length pLHR or its extracellular domain (ectodomain) have been produced in various recombinant systems. In COS cells and in the baculovirus insect cells system, the co-expression of the ecto- and endo-domains reconstituted a functional receptor where the association of the two domains seems to depend upon the presence of disulfide bridges. According to previous observations [39], synthetic peptides mimicking three regions of the ectodomain (21-38, 100-115, 250-272) were found to inhibit hormone binding and stimulation of cAMP production. Antisera raised against these peptides contained anti-peptide antibodies (Ab) able to interfere with hormone signalling. Moreover, the results of peptide mapping indicated that some peptides stretches may be more involved in signalling rather than in binding. Immunochemical mapping based on monoclonal antibodies (mAbs) was used to probe the hCG-ectodomain complex. It appeared that mAbs directed to epitopes present on the 'beta-tip' of hCG (assembled from the beta subunit loops 3 and 1, and previously designated site IIIb) and on the 'alpha-tip' (alpha subunit loops 1 and 3, site IIIa) bound to hCG-receptor complexes, whereas a conformational epitope (defined by the alpha-beta interface between beta seat belt C-terminus and alpha loop 2, site II) was masked. Interestingly, we and others previously reported that, in the hCG-full length receptor complex, site IIIa was shielded to mAb binding. A peptide mimicking the second extracellular loop (EL2) of the receptor endodomain was found to prevent the binding of a mAb directed to site IIIa, suggesting that this region of the endodomain may be interacting with the 'alpha-tip'. In the full-length, membrane anchored pLHR, the EL2 peptide inhibited hCG-induced cAMP production, but not binding. The possibility of inhibiting stimulation without inhibition of binding gives support to the 'negative specificity' hypothesis [6]. Thus, the ectodomain of the glycoprotein hormone receptors might be considered as a screening device preventing access of any glycoprotein hormone to the signalling peptide keys of the endodomain, which otherwise would be sensitive to any alpha subunit stimulation. Finally, antibody binding to site IIIa on the hCG-ectodomain complex was also hindered by an anti-peptide mAb directed against a peptide encoded by the eighth exon (pE x 8) of the LHR. This suggests that pEx8 is vicinal to the alpha-tip of hCG and to EL2 in the hCG-full length receptor complex. Altogether, these observations help to build up a topological model of the hCG-receptor complex.

Amino Acid Sequence↗
PubMed1996

Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay.

The betaA4 peptide, a major component of senile plaques in Alzheimer's disease (AD) brain, has been found in cerebrospinal fluid (CSF) and blood of both AD patients and normal subjects. Although betaA4 1-40 is the major form produced by cell metabolism and found in CSF, recent observations suggest that the long-tailed betaA4 1-42 plays a more crucial role in AD pathogenesis. Here, we established new monoclonal antibodies against the C-terminal end of betaA4 1-40 and 1-42, and used them for the specific Western blot detection. After optimizing the assay conditions, these antibodies detected low picogram amount of betaA4, and both betaA4 1-40 and 1-42 levels in CSF could be determined by direct loading of the samples. Blood levels of betaA4 1-40 and 1-42 were also determined by specific immunoprecipitation followed by Western blot detection. We found that CSF betaA4 1-42 level is lower in AD patients compared with non-demented controls, although there was a significant overlap between the groups. The level of betaA4 1-40 in CSF, and of betaA4 1-40 as well as betaA4 1-42 in plasma, were not different between AD patients and controls. Besides the 4-kDa full-length betaA4 band, we could also detect several N-terminal variants of betaA4 in CSF and plasma of both AD patients and controls. Two N-terminally truncated betaA4 species migrating at the position of 3.3 and 3.7 kDa were found in CSF, while 3.7- and 5-kDa forms were found in plasma. The relative abundance of these various species were considerably different in the CSF and plasma, suggesting that the cellular source and/or clearance of betaA4 is different in these two compartments.

Aged↗
PubMed1996

[Posterior cortical atrophy--a new dementia syndrome or a form of Alzheimer's disease?].

Posterior Cortical Atrophy (PCA) is a neurodegenerative disorder initially dominated by disturbances in higher visual functions including object agnosia, prosopagnosia, alexia, environmental agnosia and Balint's syndrome. Language, memory, insight, and judgement remain relatively preserved until late in the course. A characteristic neuroradiological finding consists of focal bilateral parieto-occipital atrophy demonstrated on MRI and CT. It was speculated that the possible underlying pathologic condition could be an atypical clinical variant of Alzheimer's disease, a lobar atrophy analogous to Pick's disease, a variant of Creutzfeldt-Jakob disease or some previously unrecognized entity. The prognostic question whether the visual agnostic symptoms are only a precursor of generalized dementia remained unsolved. The neuropsychological symptoms in these patients indicate that the occipitoparietal cortex is bilaterally affected which is in contrast to the parietotemporal distribution of lesions in Alzheimer's disease and the frontotemporal type of distribution in Pick's disease. The aim of this study was to review and analyze all cases of posterior cortical atrophy which have been reported in the literature. Up to now 58 cases of posterior cortical atrophy have been described. The first report of such a patient was given by A. Pick in 1902. The results of our analysis show that posterior cortical atrophy is mainly a presenile disorder which in most cases heralds the development of generalized dementia. The histopathological results suggest that the combination of clinical findings referred to as PCA can result from strikingly different pathological entities. However, most cases of PCA which were investigated postmortem revealed the histopathological lesion type of Alzheimer's disease. This suggests that PCA is rather a subgroup of Alzheimer's disease than an independent disease. This conclusion has some implication for the nosological classification of other localized slowly progressive syndromes such as slowly progressive aphasia. These syndromes may as well define possible clinical subgroups of the "classical" dementias. They show that the close relationship between the clinical profile and the brain regions involved does not necessarily imply a specific neuropathological process but focus the attention on the selective vulnerability of distinct neuronal systems.

Adult↗
PubMed1996

Characterization of a monoclonal antibody reacting with the free human luteinizing hormone beta-subunit.

Measurement of serum luteinizing hormone (hLH) is important for the detection and follow-up of patients with pathological processes of the reproductive axis. Detection of the uncombined form of the beta-subunit of hLH, or free hLH beta, has proved to be of clinical interest in the recognition of gonadotroph adenomas. As no monoclonal antibody specific for the free hLH beta is at present available, we elicited monoclonal antibodies using free hLH beta as an immunogen. An antibody, named BLH01, was selected for its specific binding to the free beta-subunit, and its antibody-binding site was characterized at the molecular level, emphasizing the importance of amino acid residues located between the disulfide-bonded Cys93 and Cys100. This region has been demonstrated as being particularly critical for the specific binding of lutropic hormones to their receptors. Topographic assignment of the epitope recognized by BLH01 was then achieved by cross-matching studies based on a library of antibodies directed to hLH beta, and the location of some epitopes on the three-dimensional model of the beta-subunit is proposed. A two-site immunoassay based on BLH01 as capture antibody was then developed. This assay, using BLH01, may constitute a simple, sensitive and highly specific procedure for assessing the clinical usefulness of measuring free hLH beta, particularly for the diagnosis and follow-up of patients presenting with pituitary adenomas.

Adenoma↗
PubMed1996

[Quantitative magnetic resonance tomography and the severity of deficits in dementia of the Alzheimer type].

The aim of the present study was to investigate the severity of dementia of the Alzheimer type (DAT) with respect to morphological changes revealed by quantitative magnetic resonance imaging (MRI). Seventeen patients with DAT (NINCDS-ADRDA guidelines) and 10 healthy elderly controls were included. The severity of dementia was evaluated on the Mini Mental State Examination (MMSE), the Global Deterioration Scale (GDS) and the Brief Cognitive Rating Scale (BCRS). Three-dimensional MRI sequences were acquired using a 1.5-T Siemens Magnetom. Whole-brain volume and the volume of the amygdala-hippocampus complex (AHC) were assessed using the newly developed software NMRWin. This software provides a semi-automated measure of the whole brain volume, while measurement of substructures requires manual guidance. In addition, the ventricle-brain ratio (VBR) was assessed. All morphometric parameters differed significantly between the two groups. AHC volumes discriminated best between them with only a small overlap. These findings were confirmed when only the data of the mildly demented patients were included in the analysis. The degree of AHC atrophy exceeded that of generalized cerebral atrophy. The severity of dementia as indicated by the MMSE, GDS and BCRS scores was correlated significantly with the volumes of the AHC bilaterally, but not with whole-brain volume or with VBR. These results underline the importance of the mesial temporal substructures in the etiology and progression of DAT and indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.

Aged↗
PubMed1994

Immunochemical mapping of human lutropin: II. Characterization of two monoclonal antipeptide antibodies reacting with the native beta-subunit.

To investigate the epitopes present on the beta-subunit of the human lutropin (hLHbeta) and their topographical relationship at the surface of the molecule, we produced two monoclonal antipeptide antibodies, designated LHP03 and LHP04, capable of binding to the radiolabeled 125I-hLHbeta and directed to the 43-52 and 110-117 regions of the hLHbeta, respectively. Analysis of the accessibility of the epitopes on hLH and on the beta-subunit of human chorionic gonadotropin (hCGbeta), equine LH (eLHbeta) and ovine LH (oLHbeta) indicated that: (i) LHP03 binds to both the free hLHbeta subunit and dimeric hLH whereas LHP04 binds preferentially to the free hLHbeta, (ii) LHP03 recognizes weakly the hCGbeta and oLHbeta in comparison to hLHbeta and (iii) LHP04 binds oLHbeta as well as hLHbeta but does not bind to hCGbeta and eLHbeta. The topographical relationship of epitopes recognized by LHP03 and monoclonal antibodies recognizing dimer specific epitopes on hLH allowed us to localize discontinuous antigenic sites that overlaps or are located outside the hHLbeta(43-52) region. Together, our results demonstrated that the hHLbeta(43-52) portion is accessible on both the free hLHbeta subunit and hLH whereas the COOH-terminal portion, hHLbeta(110-117), is probably buried at the alpha/beta interface of the hormone.

Antibodies, Monoclonal↗
PubMed1993

Unmasking of an immunoreactive site on the alpha subunit of human choriogonadotropin bound to the extracellular domain of its receptor.

To define the human choriogonadotropin (hCG) hormone's contact points with its receptor, we examined five monoclonal anti-hCG antibodies for their binding ability to the hCG-intact receptor complex and to the hCG-truncated extracellular N-terminal half receptor complex. hCG-producing CHO cells were transfected with the N-terminal 297 residues of the porcine LH/CG receptor and the secreted complexes were detected by two-site immunoassays based on anti-receptor and anti-hCG antibodies. Four antibodies did not show any differences toward the two types of complexes. In contrast, a particular antibody, directed to the alpha-subunit of hCG, recognized the hCG-truncated receptor complex but not the hCG-intact receptor complex. These results substantiate recent reports indicating that, if most of the whole alpha/beta dimer is bound to the N-terminal half of the receptor, some regions of the alpha-subunit might be contacting the C-terminal half.

Animals↗
PubMed1993

[Conflict regarding neurology--a study of specialty origin of clinical neurology in Germany].

Although Germany was a center of neurological research during the 19th century institutionalisation of clinical neurology was delayed in comparison to other countries. The establishment of neurology in Germany is characterised by a conflict between internists, psychiatrists and neurologists that lasted nearly a hundred years. The present study describes and analyses the motives and the course of development of this dispute. The conflict could not be solved by means of objective arguments because on the one hand nervous disease were part of internal medicine, while on the other hand the postulated identity of mental and nervous disease was the central paradigm of the academic psychiatrists. As a professional group the entry of the neurologists into the dispute was very late at a time point when the historical development was already in favour of the psychiatrists. By taking into account not only intrascientific but also political and economic factors, the dynamics of the historical process becomes comprehensible.

Conflict, Psychological↗
PubMed1993

[Not Available].

Explore the source record for details and available documents.

History, Modern 1601-↗
PubMed1991

[The neurologic department of the Neurologic Clinic--establishment of the Heidelberg Chair for Neurology 1881-1969].

During the 20th century clinical neurology developed to a fully established discipline being descended from Psychiatry and Internal Medicine. In this paper the development of clinical neurology at the University of Heidelberg from a Nervenabteilung at the clinic for internal medicine to a chair with separate clinic of neurology is outlined as an example for the controversy which accompanied the institutionalization of the discipline in Germany. Pointing out motives and arguments of the persons involved in this process the specific circumstances of the development of neurology in Germany are stated more precisely.

Germany↗
PubMed1990

[Institutional establishment of pathologic anatomy in the 19th century at universities in Germany, German-speaking Switzerland and Austria].

The institutionalization of an academic discipline in the university system is a complex process influenced by several intra- and extrascientific, personal and economic factors. Starting with pathological anatomy at the beginning of the 19th century, we analysed its development from a subsidiary to a fully established discipline. We ascertained different stages of institutionalization:lectureship, associate chair, chair, institute. At each stage we found supporting as well as hindering factors. It could be shown that the structure of the German academic system was especially conductive to the establishment of the new discipline.

Austria↗
PubMed1986

Failure of an angiotensin II antagonist to influence isoprenaline-induced antidiuresis in rats.

The purpose of this study was to elucidate the role of angiotensin II in isoprenaline-induced antidiuresis by use of the competitive angiotensin II antagonist saralasin. Isoprenaline is known to enhance the formation of angiotensin II. Since angiotensin II has been shown to increase proximal tubular salt and volume reabsorption and to decrease renal fluid and salt excretion the renal effects of isoprenaline might, at least partly, be mediated by angiotensin II. Isoprenaline, infused at 0.1 microgram/kg . min i.v. into anaesthetized rats, led to a marked decrease of urine flow, sodium and potassium excretion and to an increase in urinary osmolality, confirming previous data. Effective renal plasma flow increased significantly. Immediately after onset of the isoprenaline infusion a transient small fall in GFR was observed. On continuation of the infusion, GFR recovered, but marked antidiuresis persisted. Changes in renal hemodynamics, therefore, can be excluded as being responsible for the antidiuretic effect. Saralasin, infused at 6 micrograms/kg . min i.v., did not affect isoprenaline-induced antidiuresis, antinatriuresis, antikaliuresis, and the increase in urinary osmolality, but prevented the rise in renal plasma flow observed during isoprenaline infusion, probably as a consequence of a weak angiotensin II-like effect of saralasin on renal vessels. It is concluded that angiotensin II does not play a role in isoprenaline-induced antidiuresis. The results are compatible with the view that beta-adrenoceptor stimulation may directly affect the tubular handling of water and salt.

Angiotensin II↗
PubMedDate not supplied

Cerebral changes and cerebrospinal fluid beta-amyloid in Alzheimer's disease: a study with quantitative magnetic resonance imaging.

Pathological and biochemical studies indicate that beta-amyloid (betaA4) deposition is a hallmark in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies demonstrate that the respective cerebral changes primarily strike the temporal lobe and the amygdala-hippocampus complex and may be reliably assessed using quantitative magnetic resonance imaging (MRI). Therefore one may expect that reduced betaA4-levels are significantly correlated with measures of the temporal lobe rather than global cerebral atrophy in AD patients. To test this hypothesis in a clinical study, cerebrospinal fluid concentrations of total betaA4 and its major C-terminal variations betaA4 1-40 and betaA4 1-42 were compared with cerebral changes as assessed by quantitative magnetic resonance imaging (MRI). Significantly (P< 0.05) reduced betaA4 1-40 and betaA4 1-42 levels were found in the AD patients (17 female; six male; AD/NINCDS-ADRDA-criteria) in comparison to the patients with major depression (seven female; two male; DSM-III-R). Within the AD group, betaA4 and betaA4 1-42 levels were significantly correlated with the volume of the temporal lobes (r= 0.46 and r= 0.48, respectively) but none of the other volumetric measures. These findings indicate that changes in cerebral betaA4 levels contribute to temporal lobe atrophy in AD and support the possibility that betaA4 is central to the etiology of AD.

Aged↗
PubMedDate not supplied

In vivo quantification of brain volumes in subcortical vascular dementia and Alzheimer's disease. An MRI-based study.

Quantitative magnetic resonance imaging (MRI) was used to assess global and regional cerebral volumes in patients with a clinical diagnosis of subcortical vascular dementia (VD) and Alzheimer's disease (AD). Whole brain volume, cerebrospinal fluid volume, volumes of the temporal, frontal and parietal lobes, the cerebellum and the amygdala-hippocampus complex were determined using a personal computer-based software. Seventeen patients with VD, 22 patients with AD and 13 healthy controls were included. Analysis of covariance using age as covariate demonstrated significant mean differences between controls and dementia groups with respect to all morphological parameters. However, apart from the volume of the cerebellum no significant volumetric differences were found between VD and AD. These results indicate that MRI-based volumetry allows differentiation between AD or VD from normal controls and that measurement of cerebellar volume may be of use to separate vascular and degenerative dementia. However, since the distribution of cerebral atrophy in both dementia groups is very similar, it is suggested that the atrophic changes are not specific to the underlying cause but rather reflect the selective vulnerability of neuronal structures.

Aged↗