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Biomedical subjects

J Knowles

Publications and source records attributed to J Knowles.

25 records · Page 2Linked to original sources

Sequencing of the chicken non-erythroid spectrin cDNA reveals an internal repetitive structure homologous to the human erythrocyte spectrin.

Immunological screening of a chicken gizzard cDNA expression library was used to isolate two clones encoding a part of the non-erythroid spectrin-like protein. Clones were identified by immunoblotting of the polypeptides synthesized in Escherichia coli cells transformed with cDNA cloned in the pUC8 plasmid vector using polyclonal rabbit antibodies raised against bovine non-erythroid spectrin. The sequence of an approximately 1.5-kb cDNA insert of one clone was determined. Analysis of the predicted amino acid sequence reveals that, despite differences in immunological cross-reactivity and peptide maps, the chicken non-erythroid and the human erythrocyte spectrins are highly homologous proteins. Like the human erythrocyte spectrin, the chicken smooth muscle spectrin appears also to be constructed from repeated, homologous structures of 106 amino acid residues. This is probably a universal structure motif of spectrins.

Amino Acid Sequence

Ultrastructure of intermediate lobe of the pituitary and melanocyte-stimulating hormone secretion in oestrogen-induced kidney tumours in male hamsters.

One group of male Syrian hamsters was killed after various periods of diethylstilboestrol (DES) treatment, ranging from 6 to 36 weeks. All developed renal tumours by 24 weeks. DES also induced hyperplastic and neoplastic changes in the pars intermedia of the pituitary with proliferation of MSH-secreting cells and elevated serum MSH concentration. Another group of male Syrian hamsters was given DES for 36 weeks followed by cessation of hormone treatment. The animals were killed at various intervals from 12 to 36 weeks after DES withdrawal. In these animals the DES-induced renal tumours underwent regression whilst the pituitary changes persisted until the termination of the experiment. The findings suggested that the hormone MSH may be implicated in renal carcinogenesis but plays no role in the maintenance of the established tumours.

Animals

A reappraisal of the effects of ACTH on the response of the central nervous system to injury.

ACTH possesses powerful immuno-suppressive properties and also retards healing by inhibiting fibroblast proliferation and the deposition of collagen. In the present work this hormone was used to test both the 'barrier' and 'immune' hypotheses relating to the failure of CNS regeneration after injury, dosages being administered which had been found to stimulate maximal adrenal production of glucocorticoids in control animals. Although the scarring in the CNS and the systemic humoral and cellular immune responses were significantly depressed, no increase in CNS axon growth was noted, even when large doses of thyroxine were added. We conclude that both 'immune' and 'barrier' hypotheses should be rejected, and that the beneficial effects of thyroxine treatment reported by some workers are not substantiated.

Adrenocorticotropic Hormone

Effect of oestrogen on the pituitary gland of male Syrian hamsters. I. Electron microscope studies of pars intermedia.

The ultrastructure of the pars intermedia of normal and oestrogen-treated male Syrian hamsters is described. 3 types of cell were observed in normal gland, namely, 2 types of "light" cell and a "dark" cell. Light cells were regular in shape with round or oval nuclei and could be divided into type 1 and 2 by the size of their granules 200 to 250 nm in type 1 and 100 to 150 nm in type 2. Dark cells were fewer in number, irregular in outline with highly-indented chromatin-rich nuclei and occasional secretory granules in the Golgi area. Treatment for 6 weeks with diethylstibestrol (DES) 0.6 mg in 0.2 ml distilled water subcutaneously 3 times per week failed to induce recognisable change in the pars intermedia although after 12 weeks treatment cytoplasmic changes were observed. From that time until the experiment ended after 30 weeks of treatment progressive changes indicative of enhanced synthesis of hormone were present, greater cytoplasmic volume, hypertrophy of the Golgi apparatus, marked development of endoplasmic reticulum and ribosomes, increased numbers of secretory granules and the presence of granules within granules.

Animals

Experimental contribution to the pathogenesis of spina bifida.

Reopening of the central canal in 3-day-old chick embryos results in the development of a typical myeloschisis within 5 min. Focal continuity between the ectoderm and neural tissue at the site of experimentally induced spina bifida (SB) may be achieved in 2 hr and increases in consecutive hours. In 24 hr a secondary neuro-ectodermal junction at the site of SB is fully formed and can be misinterpreted as evidence of a failure of the neural tube to close. Therefore the continuity between ectoderm and neural tube to close. The detachment of the notochord from the open portion of the spinal cord is a secondary phenomenon.

Animals