Search PubMed⌕ Search

Biomedical subjects

C Joachim

Publications and source records attributed to C Joachim.

30 records · Page 2Linked to original sources
PubMed1991

Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques.

A central unresolved issue in Alzheimer's disease is the origin of the extracellular amyloid beta protein (A beta P) found in senile plaques and its relationship to the dystrophic neurites that intimately surround it. Here the presence and distribution within senile plaques of various epitopes of the beta-amyloid precursor protein (APP) are compared with the distribution of A beta P itself and markers for plaque neurites. Several principal findings emerge: 1) antibodies to regions of APP outside of A beta P ('APP antibodies') recognize only a subgroup of senile plaques; 2) within these plaques, APP antibodies label discrete globular and granular structures morphologically resembling neurites; 3) virtually all of the plaques labeled by APP antibodies also contain neurites reactive with antibodies to tau; 4) double labeling with anti-tau and an APP antibody shows that the neuritelike profiles stained by the APP antibody are always closely associated with tau-positive neurites within the same plaque and that a minority of profiles appear to be labeled by both antibodies; and 5) antibodies to different regions throughout APP label the same profiles within plaques, suggesting the presence of the full-length precursor. The authors conclude that only a subgroup of senile plaques contain APP epitopes and that the immunostained structures are neurites. Because many A beta P-containing plaques in neocortex, cerebellum, and striatum were found to be devoid of any APP labeling, as were vascular A beta P deposits, it is unlikely that the extracellular A beta P is principally derived from the APP found within dystrophic neurites. The immunodetection of apparently full-length APP, an axonally transported protein, in selected plaque neurites provides yet another protein marker of neuritic dystrophy, possibly indicative of an aberrant regenerative response.

Alzheimer Disease↗
PubMed1987

Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity.

Three adults with progressive cognitive decline and extrapyramidal dysfunction were studied. They were all mentally retarded women without known chromosomal abnormalities, ranging in age at the time of onset from 31 to 42 yrs with an average duration of illness of 6 yrs. Neurological signs were stereotyped and consisted of a unilateral equinovarus foot posture followed by progressive dementia, rigidity and quadriparesis. Identical pathological findings were noted in all cases. There was marked deposition of iron-containing pigments in the globus pallidus and reticulate zone of the substantia nigra. Numerous axonal spheroids were noted in these areas and in the gracile and cuneate nuclei. In addition to these typical changes of Hallervorden-Spatz disease (HSD), abundant neurofibrillary tangles (NFTs) were found within the hippocampus, neocortex, nuclei of basal forebrain, subthalamic nucleus and brainstem reticular formation. Rare Hirano bodies and granulovacuolar degeneration were noted within the hippocampus; neuritic plaques and amyloid deposits were absent. Ultrastructurally the NFTs were mostly paired helical filaments (PHFs) with a diameter of 20 to 25 nm and a half-periodicity of 80 nm. Straight filaments and incompletely twisted forms were also seen. Immunocytochemistry with polyclonal antibodies to PHFs was positive in a distribution identical to that of Bodian-positive NFTs. Biochemical analysis of frozen frontal cortex from 1 case revealed a 94% depletion of the cholinergic marker enzyme choline acetyltransferase. Somatostatin-like immunoreactivity was within normal range. Study of 1 case with laser microprobe mass analysis revealed evidence of aluminium accumulation in tangle-bearing hippocampal neurons. Adjacent tangle-free neurons failed to show comparable accumulations. These findings indicate that adult onset HSD occurring in mentally retarded individuals may represent a distinct clinicopathological entity associated with neurofibrillary pathology without amyloid deposition.

Adult↗
PubMed1983

Monocyte-induced inhibition of lymphocyte response to phytohaemagglutinin in progressive systemic sclerosis.

In patients with progressive systemic sclerosis (PSS) lymphocyte responses to phytohaemagglutinin (PHA) are abnormal (27.2 +/- 3.5 X 10(-3) counts per minute (cpm) versus 69.8 +/- 4.4 X 10(-3) for normal persons, p less than 0.005). Removal of adherent peripheral blood mononuclear cells improves the response of PSS lymphocytes (42.3 +/- 3.4 X 10(-3) cpm, 155% of control) but diminishes the response of normal lymphocytes (60.3 +/- 5.9 +/- 10(-3), 86% of control). Supernatant fluids from cultures of PSS unfractionated and adherent cells depress normal T cell response to PHA (64% and 55% of control respectively), but supernatant fluids from normal unfractionated and adherent cells do not (104% and 101% of control). Supernatant fluids of PSS and normal adherent cells, cultured in the presence of indomethacin, are not inhibitory to normal T cells (109 +/- 15% and 124 +/- 14% of control respectively). Supernatant fluids from PSS patients are more inhibitory than comparable fluids from patients with systemic lupus erythematosus (60 +/- 8% of control versus 80 +/- 5% of control). These data support the hypothesis that cellular immunity is abnormal in patients with PSS and indicate that adherent mononuclear cells mediate at least one component of the abnormality via an indomethacin-sensitive mechanism.

Dinoprostone↗
PubMed1980

Supressor monocytes in patients with systemic lupus erythematosus. Evidence of suppressor activity associated with a cell-free soluble product of monocytes.

Abnormal SLE mononuclear cell responses to PHA can be corrected by removal of adherent mononuclear cells. The present study demonstrates that cell-free supernatants from allogeneic adherent cell cultures inhibit lymphocyte response and that addition of indomethacin to cultures partly blocks the inhibitory effect of the resulting supernatant. Supernatants from SLE monocyte cultures suppressed allogeneic normal T cell responses by 36% (response in supernatant 33,515 +/- 3814 cpm, media control 51,947 +/- 3173 cpm) but normal monocyte culture supernatants did not suppress (48,384 +/- 4172 vs. 47,477 +/- 3221 cpm). Early (less than 24 hr) addition of indomethacin to monocyte cultures prevented elaboration of inhibitory material. In normals, indomethacin-treated supernatants were strikingly stimulatory (response 178% +/- 24 of control), whereas similarly treated supernatants of SLE monocyte cultures were not stimulatory (response 103% +/- 8 of control). The data indicate that a soluble inhibitor of lymphocyte blastogenesis is produced by SLE monocytes.

Adult↗
PubMedDate not supplied

Accuracy of clinical operational diagnostic criteria for Alzheimer's disease in relation to different pathological diagnostic protocols.

In this study we analysed the accuracy of two sets of clinical diagnostic criteria, the NINCDS/ADRDA and DSM-III-R, in relation to the currently used pathological diagnostic criteria for Alzheimer's disease (AD), the Khachaturian criteria, the Tierney A3 criteria and the CERAD protocol. The sensitivity of the individual clinical diagnostic criteria, NINCDS/ADRDA and DSM-III-R, is poor (34-58%) irrespective of the pathological diagnostic criteria applied for the definite diagnosis of AD. The combination of the NINCDS/ ADRDA 'possible' and 'probable dementia of the Alzheimer type' (DAT) categories has a high sensitivity (91-98%). However the combination resulted in very poor specificity (40-61 %). Thus, none of the clinical diagnostic criteria is satisfactory. We found similar results when we analysed the predictive value of these clinical diagnostic criteria. The positive predictive value of NINCDS 'probable DAT' category and that of the DAT diagnosis by DSM-III-R is very high (89-100%). This makes the use of these categories suitable for research purposes. However, the negative predictive value of both diagnoses is poor (33-63%), making these criteria unsuitable for diagnostic purposes in clinical practice.

Aged↗