Search PubMed⌕ Search

Biomedical subjects

N Marks

Publications and source records attributed to N Marks.

At least 73 records · Page 4Linked to original sources
PubMed1978

Treatment of experimental allergic encephalomyelitis with an inhibitor of cathepsin D (pepstatin).

Intraperitoneal administration of pepstatin (2 mg/day for 5 weeks) to Lewis rats subjected to experimental allergic encephalomyelitis (EAE) (induced by guinea pig spinal cord and pertussis vaccine) suppressed the appearance of clinical signs of disease, and reduced the severity and incidence of CNS lesions normally associated with this disease. Administration of pepstatin for shorter periods to Lewis rats, or BSVS mice, or guinea pigs challenged with myelin basic protein delayed, but did not prevent clinical signs of EAE, but was accompanied in all cases by a less severe histopathology.

Animals↗
PubMed1977

Lipoperoxidation in human and rat brain tissue: developmental and regional studies.

Lipoperoxidation in human and rat brain was studied on the basis of formation in vitro of thiobarbituric acid positive (TBA) materials. In rats aged 1--540 days, the endogenous pools of reactive material were unchanged but on subsequent incubation of their homogenates the level of TBA-positive materials fell by 3 fold (fresh weight basis) and 5.4 fold (protein basis). In human brain, there was a distinct regional distribution of reactive materials in the endogenous pools with highest levels in the cerebellar vermis, and lower levels in thalamus, cortical regions, substantia nigra, caudate nucleus, pallidum, putamen, and hypothalamus. Only trace levels were detected in the pineal gland. On incubation all values rose 13--25 fold within 3 h at 37 degrees C except for cerebellar vermis which was increased 6 fold, and pineal gland 9 fold. Four TBA-positive materials were separated from rat brain by TLC, three of which were identical to malonyldialdehyde and its polymers. Lipoperoxidation in rat homogenates was inhibited 75--90% by sera from several different sources. The inhibitory properties were unaffected by dialysis and were not reproduced by addition of a large number of low and high mol. wt. components including vitamin E when added in concentrations equal to or exceeding that of native serum.

Adult↗
PubMed1977

Proteolytic enzymes in ordinary, hyperacute, monocytic and passive transfer forms of experimental allergic encephalomyelitis.

The changed patterns of proteolytic activity in brain and spinal cord of Lewis rats were examined in 4 different morphological variants of EAE: ordinary induced by the standard emulsion, hyperacute induced by an emulsion plus pertussis vaccine, passive induced by donor EAE cells, and monocytic induced by treatment of passive EAE with the immunosupressive drug tilorone. The following enzymatic changes were found: firstly, in ordinary EAE there was a 2--3.5-fold increase in cathepsins A and C (E.C. 3.4.14.1) in spinal cord one day following the appearance of paralysis with a smaller change in hindbrain, and none in the forebrain regions. With recovery from paralysis, levels of cathepsin A remained high in upper cord, and cathepsin C levels fell to about half. In contrast, increase in cathepsin D(E.C. 3.4.23.5) was smaller and occurred only 4--5 days after paralysis with the largest change in spinal cord areas and with only a small decrease on recovery from paralysis. Secondly, in hyperacute EAE, the increase in all cases was smaller with the largest change in cathepsin A level in upper spinal cord. In passive EAE, the most significant increase occurred only in the lower spinal cord for cathepsins A and C, and fourthly, in monocytic EAE induced by tilorone, there was an exceptionally large, 3-fold increase in cathepsin C in lower cord as compared to a 1.5-2 fold increase for other cathepsins. No major differences were observed on comparison of antigens from different sources (guinea pig and bovin spinal cord myelin peptide). An attempt is made to relate enzymatic changes to the morphological features of each variant with special reference to the nature of the infiltrating cells.

Acute Disease↗
PubMed1976

The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen?

Microinjection of the C-fragment (also called beta-endorphin), which is amino acid sequence 61-91 of the endogenous pituitary hormone, beta-lipotropin (beta-LPH), in the periaqueductal gray of the rat resulted in profound sedation and catalepsy, while microinjection of smaller fragments-that is, methionine-enkephalin [sequence beta-LPH-(61-65)] and its related pentapeptide, leucine enkephalin, and alpha-endorphin [sequence beta-LPH-(61-76)] resulted in attenuated forms of this behavior. This indicates that the C-fragment is an important neuromodulator of the central nervous system. The similarity of this behavior to that seen after systemic administration to experimental animals of exogenous neuroleptics suggests that a disturbance in the bioavailability of this neuropeptide to receptor sites in brain-perhaps due to lack of enzymatic cleavage from the circulating parent hormone, beta-lipotropin--may be an etiological factor in those psychopathological states for which the exogenous neuroleptics exert an ameliorative influence.

Analgesia↗
PubMed1976

Glycine levels in the degenerated human spinal cord.

Tissues from non-degenerated tissue of 18 patients were assayed for glycine concentration in grey and white matter in the thoracic, cervical and lumbar regions. Confirming earlier results, glycine concentration was found to be maximal in the grey matter of the lumbar segments of the lateral column. Analysis of tissue from 11 human spinal cords showing unilateral Wallerian degeneration, 4 cords with amyotrophic sclerosis and 4 cords with bilateral Wallerian degeneration failed to show statistically significant differences when compared with control values. The results argue against a supraspinal origin of glycine and suggest that glycine levels are regulated locally or at a segmental level in the spinal cord in man.

Adult↗
PubMed1975

Changes in proteolytic enzymes and proteins during maturation of the brain.

(1) Changes during development in the levels of proteinases and peptidases were measured in brain homogenates. At all ages di- and tripeptidase levels were 7-15-fold higher than proteinase activity. (2) Cathepsin A and D and neutral proteinase activity first decreased (during the 5 days before birth) and then increased (primarily during the first 10 days after birth) in development. The total enzyme content per unit weight of brain did not change greatly after 10 days, although specific activity fell owing to an increase in protein in older animals. (3) The developmental pattern of activities or peptidases measured with Leu-Gly and Leu-Gly-Gly and of arylamidases measured with Arg- and Arg-Arg-beta-naphthylamides was similar to that of proteinases. Total and specific activities increased rapidly after birth; then total activity did not change and specific activity decreased. (4) The proteinase content of tissue fractions (nuclear and lysosomal-mitochondrial) similarly reached a maximal peak in the rapid growth phase of the brain. (5) The decrease of hydrolytic activity after 10 days of age seems to parallel a decrease in the rates of protein breakdown in vivo, showing parallel behavior with decreasing protein turnover. In contrast, during the first 10 days of life protein turnover and calculated rate of protein breakdown in vivo decrease while the level of hydrolytic enzymes increases.

Amino Acids↗
PubMed1975

Significant differences in the degradation of pro-leu-gly-nH2 by human serum and that of other species (38484).

The acyclic C-terminal tripeptide of oxytocin, H-Pro-Leu-Gly-NH-2, is not degraded upon incubation with human (male,female or pregnant female) plasma or serum for 1hr at 37 degrees. However, the sera of other species tested, including rat, chicken and carp, degrade this tripeptide 100%, 4% and 30%, respectively, in 1 hr, as determined by quantitative amino acid analysis of released products. Among the species studied there seems to exist a correlation between the anatomic development of the pars intermedia and the ability of the serum to hydrolyze H-Pro-Leu-Gly-NH-2, which has been proposed to be a MSH-release-inhibiting factor. The only identified degradation products are Pro, Leu and H-Gly-NH-2 with no detectable levels of H-Leu-Gly-NH2. The dipeptides H-Leu-Gly-NH-2 and H-Pro-Leu-OH are each cleaved at similiar rates in either human or rat serum, although the rate of hydrolysis of both peptides is lower in human than in rat. Thus, it does not appear that the dipeptide, H-EU-Gly-NH-2, can accumulate as one of the breakdown products of the tripeptide. The arylamidase present in rat serum has different characteristics from the enzyme in rat brain which can degrade H-Pro-Leu-Gly-NH-2.

Aminopeptidases↗