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Biomedical subjects

K A Ansari

Publications and source records attributed to K A Ansari.

11 recordsLinked to original sources

Qualitative and quantitative studies on human myelin basic protein in situ with respect to time interval between death and autopsy.

Normal human frontal lobe white matter obtained at autopsy was used to determine the extent of in situ post-mortem degradation of myelin basic protein (BP). Effects of the following two factors were studied: 1) time interval between death and autopsy, and 2) freezing and thawing the tissue. Quantitative extraction of BP from the autopsy material showed only minimal loss of BP that could be attributed to the time interval between death and autopsy (up to 48 h). The purified BP from these samples was electrophoresed on acrylamide gels at pH 4.3 and it was found that the electrophoretic patterns were comparable to zero hour bovine BP samples. The BP obtained from the autopsy samples was found to be encephalitogenic in guinea pigs. When tested against rabbit anti-human-BP serum, the purified BP preparations gave a single arc in immunoprecipitin test. BP extracted and purified from tissue that was frozen once and processed before it could thaw showed yields, encephalitogenic activity and acrylamide disc gel electrophoretic patterns that were similar to those of BP from tissue that was never frozen. However, frozen tissue that was thawed and then incubated for 8 h at room temperature before processing yielded only 13-25% of the total extractable protein. This BP also was encephalitogenic and showed acrylamide banding pattern that was similar to BP from tissue that was never frozen. Samples of white matter were examined by electron microscope. Unfrozen autopsy material showed some separation of myelin lamellae. Myelin in sections of frozen and thawed white matter showed separation as well as disruption of the lamellae. Samples that were frozen, thawed and then incubated at room temperature for 8 h showed sporadic loss of dense line material in addition to lamellar separation and disruption. The results a) show that BP is quite resistant to autolytic changes and b) are consistent with the location of BP along the cytoplasmic surface of the myelin membrane.

Aged

Circulating IgE, allergy and multiple sclerosis. Serum levels of IgE, other immunoglobulins and complement (C's) in patients with multiple sclerosis in exacerbation and other neurologic diseases.

Serum levels of IgE, other immunoglobulins and C'3 were measured in 36 MS patients, and the results compared with those of 40 age- and sex-matched patients hospitalized on Neurology Service. Diagnoses among controls included cerebral infarction, cervical spondylosis, nonmigrainous headache, seizure disorders and peripheral neuropathy. Six patients in the MS group and seven in the non-MS group had a past history of allergy to food, drugs, dust or other substances. IgE levels were measured by double-antibody radioimmunoassay. Other immunoglobulins (G, M, D and A) and C'3 were quantitated by Mancini's method. Results indicate that the median IgE and C'3 levels of MS patients were slightly lower than those for non-MS subjects. Concentrations of other immunoglobulins were similar for the two groups. CSF samples from 12 MS and five non-MS patients were studied and none of these contained measureable (greater than 7.5 U/ml) IgE. In view of: 1) recent reports describing mast cells in MS plaques, 2) the suggested role of biogenic amines in the pathogenesis of demyelinating diseases, and 3) because IgE exists in free and cell bound state, it is suggested that tissue surveys of MS plaques for IgE deposits similar to those seen in glomeruli in nephrotic syndromes may provide a clue to the pathogenesis of MS.

Adult

Olfaction in multiple sclerosis. With a note on the discrepancy between optic and olfactory involvement.

Serial binary dilutions of amyl acetate and nitrobenzene were used in a double-blind test to determine olfactory acuity of 40 multiple sclerosis (MS) patients. Similar determinations were made on 24 age- and sex-matched controls. Results of repeated measurements on 18 patients indicated that the methodology was reliably reproducible. When mean olfactory threshold on MS patients was compared with that of the controls no differences could be found. Among the MS patients, olfactory threshold did not vary with the presence or absence of optic involvement and correlated poorly with the degree of disability. These results are in disagreement with those of WENDER and SZMEJA who reported olfactory dysfunction in 18 out of 52 MS patients. Our findings are compatible with the observations of ZIMMERMAN and NETSKY who failed to find any plaques in olfactory tracts of MS brains. The significance of this disparity between involvement of optic and olfactory systems, both of which contain central myelin, is discussed. Available biochemical evidence suggests that, as postulated by LUMSDEN, sparing of olfactory tracts may in part be related to the relatively lower basic protein content of these structures.

Adrenocorticotropic Hormone

Decreased myelin basic protein content of the aged human brain.

Myelin basic protein was extracted from frontal lobe white matter obtained at autopsy from seven individuals ranging in age from 72 to 78 years. Qualitative and quantitative comparisons were made between basic protein from this group and that extracted from another group of individuals ranging in age from 45 to 65 years. The basic protein content of the older brains was considerably lower than that of the younger brains. Qualitative studies that included assay for encephalitogenic activity, disk gel electrophoresis at pH 4.3, and immunoprecipitation did not reveal any difference in the basic protein derived from the two age groups. Possible factors that may help explain the decreased basic protein content of the aged brain are discussed.

Aged

Quantitative estimation of cerebrospinal fluid globulins in multiple sclerosis. A comparison of electrophoretic and immunologic methods.

CSF samples were obtained from 44 multiple sclerosis patients during exacerbation and from 50 age and sex-matched non-multiple sclerosis controls. In an attempt ot select the most suitable test for diagnosis of multiple sclerosis, each sample was analyzed by three methods: (1) electrophoresis, (2) electroimmunodiffusion, and (3) radial immunodiffusion (RID). Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded positive results in 50, 55, and 59 percent of the multiple sclerosis patients respectively. Electrophoresis, electroimmunodiffusion, and radial immunodiffusion yielded 10, 12, and 8 percent false positives (beyond mean +/- 1 S.D.) respectively. Thus the three tests did not differ much with regard to yield of true or false positive results. When factors such as simplicity, time and equipment involved, and the interval between the test and results are taken into account, radial immunodiffusion appears to be most suitable for an avverage CSF diagnostic laboratory. For a laboratory with special interest in multiple sclerosis, agarose gel-electrophoresis of concentrated CSF appears to be the test of choice.

Adult

Electrophoretic and morphologic studies on normal human white matter obtained at surgery with special reference to its basic protein component.

Histologically confirmed normal pieces of human white matter removed during surgical approach to underlying pathology were studied by acrylamide disc gel electrophoresis and electron microscopy. A basic electrophoretic pattern of the white matter homogenates from three separate patients is described. Aliquots of white matter from two of these patients were incubated at 4 degrees C and 23 degrees C for intervals up to 18 hours, then homogenized and electrophoresed to detect any degradative changes in the basic protein band. Results of these studies indicated that the basic protein band of freshly obtained normal human white matter was unaffected by incubation at 23 degrees C for as long as 18 hours. Electron microscopic examination of white matter that was incubated for 2 hours at room temperature prior to fixation, showed sporadic areas of lamellar separation, a finding similar to but not as extensive as that described earlier in white matter obtained at autopsy that was performed 8 hours post-mortem. These findings 1) confirm earlier observations made on autopsy material, 2) are compatible with location of basic protein along the cytoplasmic surface of myelin lamellae, and 3) further emphasize the remarkable resistance of basic protein in situ to autolytic degradation.

Adult

Biochemical and immunological studies with human optic and olfactory tracts.

Clinical and pathological studies have revealed that in multiple sclerosis (MS) the involvement of the optic tracts is much more frequent than that of the olfactory tracts. To investigate the possible reasons for this difference in involvement of these two adjacent structures, both containing a central type myelin, we have studied optic and olfactory tracts obtained at autopsy from 7 adult males ranging in age from 54 to 64 years. White matter from the frontal poles of the same individuals was used for reference. These tissues were compared with respect to the relative content of a) water, b) soluble proteins, c) 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity, and d) immunologically precipitable basic protein (BP). Homogenates from these tissues were further compared by disc gel electrophoresis in two systems; phenolformic acid-water and SDS-urea gels. Results indicate that while the optic tracts and the frontal pole white matter were similar with respect to their water, total protein content and BP content, the optic tracts had lower CNP activity than the frontal poles. The olfactory tracts contained more water and less BP and the CNP activity of these structures was lower than that of the frontal pole white matter. Assuming the CNP activity and the BP content are true measures of the total myelin content of a given tissue, it appears that olfactory tracts have smaller amounts of myelin. On the other hand, the optic tracts contain only half as much CNP-activity with a disproportionately greater amount of BP. The possible significance of these findings is discussed.

Animals