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Biomedical subjects

G Escher

Publications and source records attributed to G Escher.

25 records · Page 2Linked to original sources

The agrin gene codes for a family of basal lamina proteins that differ in function and distribution.

We isolated two cDNAs that encode isoforms of agrin, the basal lamina protein that mediates the motor neuron-induced aggregation of acetylcholine receptors on muscle fibers at the neuromuscular junction. Both proteins are the result of alternative splicing of the product of the agrin gene, but unlike agrin, they are inactive in standard acetylcholine receptor aggregation assays. They lack one (agrin-related protein 1) or two (agrin-related protein 2) regions in agrin that are required for its activity. Expression studies provide evidence that both proteins are present in the nervous system and muscle and that, in muscle, myofibers and Schwann cells synthesize the agrin-related proteins while the axon terminals of motor neurons are the sole source of agrin.

Agrin↗

Agrin isoforms and their role in synaptogenesis.

Agrin is thought to mediate the motor neuron-induced aggregation of synaptic proteins on the surface of muscle fibers at neuromuscular junctions. Recent experiments provide direct evidence in support of this hypothesis, reveal the nature of agrin immunoreactivity at sites other than neuromuscular junctions, and have resulted in findings that are consistent with the possibility that agrin plays a role in synaptogenesis throughout the nervous system.

Agrin↗

Excessive numbers of axons after early enucleation and blockade of metamorphosis in the oculomotor nerve of Xenopus laevis.

The number of axons in the oculomotor (OM) nerve of Xenopus laevis tadpoles was counted in unoperated and in unilaterally enucleated animals, raised in 0.4 g/l thiourea (TU), a thyroid-blocking agent, which arrested their development at premetamorphosis. In unoperated animals the number of axons starts to decrease with metamorphosis. When raised in TU, the tadpoles do not metamorphose and show no axon loss; rather, there is a moderate increase in axon number (13%) after 6 months of thiourea-treatment. Thus metamorphosis is necessary for the initiation of axon loss. In unilaterally enucleated tadpoles, increased axon loss occurs at metamorphosis in the OM nerve of the operated side, but the contralateral OM nerve shows no loss at all. When these animals are treated with TU, there is, as compared with the effects of the TU-treatment in unoperated animals, an increase of 7% in the ipsilateral side and of 28% in the contralateral one. Thus thyroxine blockade prevents the effects of unilateral enucleation and induces an excessive number of axons during the period observed. We postulate that through blockade of metamorphosis, axon elimination is arrested, while their production continues, and that these effects are accentuated by manipulation of the axonal target.

Age Factors↗

The time course of the changes in axon number of both oculomotor nerves in normal and unilaterally enucleated Xenopus laevis.

UNLABELLED: In this paper we analyze long-term changes, extending into adulthood, of the number of axons in the oculomotor nerve of Xenopus laevis. We counted the number of axons in that nerve in normal control (nor) animals, and on the operated (ipsilateral, ip) and contralateral (co) sides of enucleated animals at premetamorphosis, metamorphic climax, juvenile (3 and 7 months) and adult (16.5 months) stages. The experimental animals had had one of their ocular primordia removed at hatching. In the nor-nerves there is a loss of 23% of the axons between premetamorphosis and climax, then a further drop of 35% by the 3-month stage, followed by a gain of 39% on reaching adulthood. At premetamorphosis the ip-nerves already contain less than the normal number of axons, which is reduced a further 73% by 3 months; there is no subsequent increase in adulthood. The co-nerves lose no axons from premetamorphosis to climax; they therefore have 30% more axons than normals; this excess is kept until 7 months; from then to sexual maturity the increase is only 11%. CONCLUSIONS: (1) unilateral target removal affects also the nerve innervating the contralateral target: the increased loss of axons on the operated side is accompanied by reduced loss on the other; (2) the contralateral side displays for some time an excess of axons compared to normal, but this is finally cancelled out by the addition of many axons in the adult nor animals; (3) adjustment of axon number is not restrained to embryonic stages but continues at least until sexual maturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Axon number in oculomotor nerves in Xenopus: removal of one eye primordium affects both sides.

Unilateral removal of one eye primordium from Xenopus laevis embryos affects the number of axons in both oculomotor nerves: on the side of the operation, we observed a substantial decrease, and on the contralateral side an increase of over 30%. Mechanisms that may be invoked to explain this striking increase are: sprouting, rerouting of axons, decreased death of the motoneurones involved, and abnormal survival of ephemeral axon collaterals.

Animals↗

Detergent-soaked HRP-chips: a new method for precise and effective delivery of small quantities of the tracer to nervous tissue.

We dissolved horseradish peroxidase (HRP) in a 5% aqueous detergent solution (Nonidet P-40) and dried it to a solid mass which was then fragmented into small chips of convenient size. These were applied to the cut or crushed oculomotor nerves of Xenopus laevis tadpoles. This method combines the advantages of solid HRP (high concentration) and the presence of a detergent (enhanced uptake). Moreover, as compared to chips of HRP alone, addition of the detergent facilitated the manipulation of the chips.

Animals↗

Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.

In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)

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