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Biomedical subjects

Fred C Westall

Publications and source records attributed to Fred C Westall.

6 recordsLinked to original sources
PubMed2006

Abnormal hormonal control of gut hydrolytic enzymes causes autoimmune attack on the CNS by production of immune-mimic and adjuvant molecules: A comprehensive explanation for the induction of multiple sclerosis.

Multiple sclerosis (MS) is generally thought to be caused by an autoimmune attack on central nervous system (CNS) myelin. A microorganism containing a mimic of an immunogenic region of a myelin protein initiates the autoimmune process. However, no specific "MS" microorganism has been found. Recently a large number of normal human gut bacteria were found to possess different encephalitogenic mimics. A hypothesis is presented that the autoimmune process is started by abnormal proteolytic digestion of these bacteria. Sufficient quantities of the mimics are produced to be recognized by the immune system. Since proteolytic processes in the gut are strictly controlled, it is proposed that the MS process is triggered by abnormal hormonal control of gut proteolytic enzymes. It has previously been suggested that the recognition of CNS myelin antigens by activated MS immune cells is facilitated by proteolytic processing of myelin proteins. The CNS proteases are also under rigid control and these control processes are the same as is in the gut. Therefore, MS clinical activity is the result of improper hydrolytic degradation in the brain-gut axis caused by an abnormal hormonal variation.

Autoimmune Diseases↗
PubMed2006

Cell proliferation inhibition in remitting multiple sclerosis CSF.

Sixty percent of the CSF samples from 21 multiple sclerosis (MS) patients in remission inhibited cellular proliferation of a variety of neuronal and glial cell lines. No inhibition was observed with CSF from relapsing or progressive MS patients (0/19). Two of 82 samples from stationary MS patients were positive. No inhibition was found in MS sera. The CSF samples had no effect on myelination of mouse organotypic cerebellar cultures. Like MS cellular proliferation and subsequent lesion formation, the 'deactivation' of the lesion also is an active defined process, rather than just the cessation of the immunological events. Furthermore, approximately 20% of samples from Huntington's, Alzheimer's and Parkinson's disease patients were also positive. However, no inhibition was seen in CSF from amyotrophic lateral sclerosis patients or controls.

Adolescent↗
PubMed2006

Molecular mimicry revisited: gut bacteria and multiple sclerosis.

Molecular mimicry is a possible explanation for autoimmune side effects of microorganism infections. Protein sequences from a particular microorganism are compared to known autoimmune immunogens. For diseases such as multiple sclerosis (MS), where the infectious agent is unknown, guesses to its identity are made. Mimics are assumed to be rare. This study takes a radically different approach. Reported sequences from all known human bacterial and viral agents were searched for autoimmune immunogen mimics. Three encephalitogenic peptides, whose autoimmune requirements have been studied extensively, were selected for comparison. Mimics were seen in a wide variety of organisms. For each immunogen, the mimics were found predominantly in nonpathogenic gut bacteria. Since the three immunogens used in this study are related to MS, it is suggested that a microorganism responsible for autoimmune activity in MS could be a normally occurring gut bacterium. This would explain many of the peculiar MS epidemiological data and why no infective agent has been identified for MS and supports recently found MS gut metabolism abnormalities.

Amino Acid Sequence↗
PubMed2005

Histo-clinical variation in multiple sclerosis: Heterogeneous proteolytic immunogenic processing.

Multiple sclerosis (MS) presents an incredible histo-clinical variation. It consists of an unpredictable series of relapses, remissions and stationary phases. The initial symptoms vary considerably. Any hypothesis of the pathology of MS must include an explanation of this oddity. Current theory suggests that MS is a collection of diseases which produce generally the same result. However, this is not a satisfactory explanation. MS appears as an enormous continuum of disease paths rather than a finite group of well-defined courses. A hypothesis is presented that histo-clinical variation in MS is due to variable proteolytic processing of several potential immunogens. MS is generally thought to be caused by an autoimmune attack on myelin components. Several myelin proteins, myelin basic protein, lipoprotein, oligodendrocyte related glycoprotein and oligodendrocyte basic protein, are encephalitogenic. Within these proteins are short sequences, which themselves are encephalitogenic. In order for potential immunogens to be "seen" by the immune system they first must be processed. This processing is performed by intracellular and extracellular proteases. A large number of different proteases are located throughout the central nervous system. Their concentrations vary with location and time. Most are under strict control. While myelin has a consistent structure, the action of proteases can present variable concentrations of immunogenic peptides. Because of the differences in location, concentration and control of the central nervous system's (CNS) proteases, the same potential immunogen could be presented to the immune system in different locations within the CNS at different times. At a given time and location, the immune system may be presented with no potential immunogens, one potential immunogen or possibly many immunogens. Therefore, because of the dynamic characteristic of presentation, one would expect to see the initial MS symptoms to be variable. This variability would be continued with subsequent symptoms. This is what is seen in multiple sclerosis. A procedure for testing this hypothesis is presented.

Central Nervous System↗
PubMed2005

Molecular mimicry or structural mimicry?

"Molecular mimicry" should be changed to "structural mimicry". The immune system recognizes shapes--three-dimensional shapes--not sequences. For two sequences to act biologically similar they must possess similar three-dimensional structures.

Amino Acid Sequence↗