Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.

Acute-Phase Proteins↗

PubMed1992

Haloperidol induced CSF protein variations in schizophrenic patients: as studied by two-dimensional electrophoresis.

High resolution two-dimensional electrophoresis of cerebrospinal fluid (CSF) from 10 schizophrenic patients demonstrated a 21% average difference in the number of proteins which could be detected in patients undergoing haloperidol therapy when compared with CSF from the same patients after withdrawal from neuroleptic treatment. Proteins affected were trace proteins, as we found no significant variation in either the total CSF protein content or the integrated protein density on each electrophoretic gel. Three mechanisms which might account for these observations are: (1) a small change in liver protein synthesis or degradation would have little if any visible effect on the concentration of major blood or CSF proteins, such as albumin, but it could significantly alter trace proteins, such as alpha 2-haptoglobin, since their concentrations are orders of magnitude less than that of the major proteins, (2) haloperidol might alter the blood-CSF protein filtration system which could affect the visibility of the trace proteins, and (3) proteins synthesized in the Central Nervous System (CNS) or enhanced in the CSF could be differentially affected by haloperidol. While additional research will be required to determine the basis for the effects of haloperidol on CSF proteins, the current studies provide information which may be helpful in delineating disease specific protein alterations from those induced by drug therapy.

Adult↗

PubMed1991

A lifetime of retinal light exposure does not appear to increase mitochondrial mutations.

Recently, there have been a number of reports of an accumulation of mutations in the mitochondrial (mt) genome with age. Such mutations may be due in part to the mt oxidative metabolic pathways which provide most of the cell's energy, but also generate free radicals. In addition, the mt genome in some tissues, such as the retina, may also accumulate mutations from the effects of ultraviolet light. To obtain information concerning the possible accumulation of retinal mt mutations with age, we cloned retinal mt DNA from a 71-year-old person. Thirty-two kilobases of sequence from 83 independently isolated clones representing two regions, a coding and a noncoding region, of the mt genome were obtained. Three polymorphisms between these sequences and the standard 'Anderson sequence' were discovered. Only one heteroplasmic mutation was found. These results confirm the low somatic mutation rate found in prior studies utilizing different types of human tissues. In addition, these results suggest that there is little if any accumulated damage to the mt DNA of the retina during normal aging.

Aged↗

PubMed1991