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Biomedical subjects

D North

Publications and source records attributed to D North.

At least 19 recordsLinked to original sources
PubMed1992

Ontogeny of epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor, and thyroid hormone receptor RNA levels in rat kidney and changes in those levels induced by early thyroxine treatment.

Ontogenic changes in the mRNA levels of epidermal growth factor (EGF), transforming growth factor-alpha, EGF receptor, and thyroid hormone receptor (r-erbA) were examined in developing rat kidneys. The mRNA levels of both EGF and thyroid hormone receptor rose dramatically during the postnatal period with the rise in thyroid hormone receptor message preceding the rise in EGF message. In addition, we examined renal mRNA levels in 1-wk-old rats treated with thyroxine (T4) from birth through d 6. Neonatal T4 treatment augmented the renal mRNA levels of EGF but decreased the levels of EGF-receptor and transforming growth factor-alpha. T4 treatment did not significantly affect the levels of renal mRNA for thyroid hormone receptor. Although the EGF and transforming growth factor-alpha peptides are similar and interact with the same receptor, our findings indicate that these homologous growth factors are regulated differently during development. In addition, hormones that influence growth and development, such as T4, may function both as positive and negative regulators of growth factor expression.

Age Factors↗
PubMed1991

The functional significance of biochemical alterations in streptozotocin-induced diabetes.

These experiments examined the effects of restraint stress on dopamine (DA) and 5-hydroxytryptamine (5-HT) and their principal metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, in 4 brain regions, as well as on plasma corticosterone concentration (CORT) and behavior in streptozotocin-induced diabetic rats and nondiabetic controls. Diabetic rats had widespread reductions in DA and 5-HT turnover (DOPAC/DA and 5-HIAA/5-HT ratios). Restraint led to equivalent increases in DA turnover in diabetics and nondiabetics, but attenuated increases in 5-HT turnover in diabetic rats. CORT concentration of diabetics and nondiabetics measured in complete quiet did not differ. Relative to these measures, only diabetics had elevated CORT when either restrained or kept in the same room with restrained rats with food and water removed. Open-field exploration was suppressed by restraint in diabetics only. All diabetic rats showed decreased locomotion in a novel environment which was normalized during a second exposure to the apparatus. Together, these results suggest that diabetes-induced disruptions in open-field activity are related to anxiety rather than to motor or energy deficits, and may be related to impaired 5-HT and CORT systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Thyroid hormone receptor and receptor-related RNA levels in developing rat brain.

The proto-oncogene c-erbA and its analogues are genes that encode thyroid hormone receptors. In rats, at least two loci have been identified by their homology to c-erbA. Each locus can produce at least two distinct mRNA species via RNA processing. However, one of those transcripts, r-erbA alpha-2, does not yield a triiodothyronine (T3)-binding protein when translated in vitro. Proper development of the rat brain is thyroid hormone-dependent during the perinatal period and there is a documented increase in brin nuclear T3-binding capacity during that time. By hybridizing cDNA probes specific to various rat erbA-like transcripts with RNA extracted from developing rat brain, we sought changes in thyroid hormone receptor mRNA levels that correspond with changes in T3-binding capacity in rat brain during the perinatal period. Three mRNA of the erbA family showed variations in relative abundance during brain development. Oddly, r-erbA alpha-2, a variant that does not code for a T3-binding protein, was the most abundant erbA-like RNA to correlate with the reported changes in T3-binding capacity. The message for rat r-erbA alpha-1 that encodes a functional T3 receptor also varies with T3-binding capacity but at a level that is at least 8-fold lower than the r-erbA alpha-2 message. The level of rat erbA beta-1 message also varies in rat brain during the perinatal period but not in a way that correlates with changes in T3-binding capacity.

Animals↗
PubMed1988

Affinity labeling of the P site of Drosophila ribosomes: a comparison of results from (bromoacetyl)phenylalanyl-tRNA and mercurated fragment affinity reactions.

The binding site of the peptidyl group of peptidyl-tRNA in the P site of Drosophila ribosomes was probed with (bromoacetyl)phenylalanyl-tRNA (BrAcPhe-tRNA). This affinity label binds specifically to the P site by virtue of its ability to participate in peptide bond formation with puromycin following its attachment to ribosomes. As many as nine ribosomal proteins may be labeled under these conditions; however, the majority of the labeling is associated with three large-subunit proteins and two small-subunit proteins. Two of the large-subunit proteins, L4 and L27, are electrophoretically very similar to the proteins labeled by the same reagent in Escherichia coli ribosomes L2 and L27. Reexamination by a different two-dimensional gel system of the ribosomal components labeled by a second P site reagent, the 3' pentanucleotide fragment of N-acetylleucyl-tRNA which is derivatized to contain mercury atoms at the C-5 position of all three cytosine residues, shows two major and three minor labeled proteins. These proteins, L10/L11, L26, S1/S4, S13, and S20, are likely present in the binding site of the 3' end of peptidyl-tRNA, a site that appears to span both subunits. These results have allowed us to construct a model for the protein positions in and near the peptidyl-tRNA binding site of Drosophila ribosomes.

Affinity Labels↗
PubMed1987

Prospective study of symptoms and signs in acutely ill infants in general practice.

A study was made of all cases of acute illness in infants aged 6 months or less presenting in a Gosport practice over five months. The frequency in these patients of the well defined symptoms and signs suggested to be important by the preliminary report of the Department of Health and Social Security's multicentre study of postneonatal mortality was recorded. During the study period there were 161 infants of this age in the practice, who gave rise to 69 consultations with acute illness. Thirty eight of these were given drug treatment and five were referred to a paediatric unit, one of them on social grounds. There were no infant deaths in the practice (total population 11,400), but two occurred in the Gosport area (total population 83,000). It would be unrealistic to refer all patients with any one of the symptoms and signs, even when well defined, in the age group 6 months or less. Analysis of the symptoms and signs found in those children who required admission did not show any pattern differentiating them from those who did not. Although the symptoms and signs studied are of value in assessment and should be sought in these patients, they cannot be used singly or in any pattern to indicate referral per se.

Acute Disease↗
PubMed1982

Cell-type specific codon usage and differentiation.

This paper presents evidence derived from the selective use of codons in ca. 40 eukaryotic genes (or messages derived from them) that codon usage is one of the most conserved features of messages for specific cell products. The theory has been developed by several investigations that the kinds of products of many if not most kinds of differentiated cells is determined by the pattern of translation abilities each cell possesses as it differentiates. A correllary of this thesis is that the groups of code words used for products of specific cell types, INDEPENDENTLY OF THE SPECIES INVOLVED, should exclude specific kinds of code words in one cell type and not another. To test this thesis, the specific frequency of codon usage and non-usage has been collated from the recently published literature and subjected to appropriate computer analysis. We find that: (1) certain codons are not used at all in any message for globins; (2) the pattern of codon usage is characteristic of specific products from specific embryonic derivatives, e.g. erythrocytes; (3) that certain code words are discriminated against generally in nearly all vertebrate cell messages evaluated; and (4) that the cell type from which a message is derived can be identified, at least in the case of 9 globin messages derived from species separated by millions of generations, purely on the basis of codon usage. From these studies it can be inferred that some evolutionary factor prevents the use of "forbidden" code words in specific kinds of cells. We propose that this factor derives from the fact that a "silent" mutation to a code word which is untranslatable by a differentiated cell will be lethal in the homozygous condition and that the thesis that so-called "codon restriction" is an important determinative factor in limiting what differentiating cells can synthesize in many kinds of developing cells explains the available evidence more adequately than alternative theories.

Animals↗
PubMed1978

Modification by suppressor cells and serum factors of the cell-mediated immune response in experimental pyelonephritis.

A marked suppression of the thymusderived (T)-lymphocyte response to concanavalin A has been demonstrated in vitro during renal infection. Suppression of the T-lymphocyte response in vitro was seen as early as 2 h after the induction of renal infection, but maximum suppression was found 24-72 h later. A population of suppressor cells in the splenic lymphocyte population, generated during the host's response to infection, contributed to the depressed lymphocyte response. Removal of suppressor cells restored the mitogenic responsiveness of the remaining splenic lymphocytes. Conversely, in co-culture experiments, a suppressor cell present in the splenic lymphocyte population of pyelonephritic animals was shown to be capable of suppressing the mitogenic responsiveness of normal splenic lymphocytes. Significantly reduced host vs. graft responses by the pyelonephritic animals confirmed, in vivo, the depression of cell-mediated immune mechanisms. An additional suppressive factor was found in the serum of pyelonephritic animals which depressed in vitro the mitogenic responsiveness of splenic lymphocytes from normal animals. Support for the suppressive role of this serum factor was found when splenic lymphocytes from pyelonephritic animals were tested in vivo in the absence of homolgous serum (graft vs. host). Under these conditions, the lymphocytes showed an enhanced reaction compared with lymphocytes from normal animals. The presence of a suppressor cell population and a serum factor, both capable of depressing cell-mediated mechanisms, may be major factors contributing to the establishment of infection in the kidney.

Animals↗
PubMed1976

A case of twin chimerism.

A case of twin chimerism is presented and shown by cytogenetic studies, red cell grouping, and white cell HL-A typing. The sex of each twin is confirmed by examination of buccal smears and their chimeric state is confirmed by non-reactivity in the mixed lymphocyte culture system. The results of these investigations are discussed.

Chimera↗
PubMed1975

Acquiescent renal infection.

The relationship between bacterial infection of the renal parenchyma with Escherichia coli and the establishment of pathologic lesions has been investigate experimentally. Infection was established in one kidney and the bacteriologic, pathologic and immunologic features of infection were compared in the pyelonephritic and contralateral unmanipulated kidney. Whereas active bacterial infection was associated with pathologic changes in the pyelonephritic kidney, a poor correlation was found between bacterial growth and the gross pathology and histopathologic changes in the contralateral kidney. The conclusion from these studies is that infection of the kidney is not always associated with pathologic changes. The term "acquiescent infection" has been used to describe this host-parasite relationship in which active, persistent, bacterial infection is not associated with pathologic lesions. Evidence is presented that bacteria in the contralateral unmanipulated kidney are present in the renal parenchyma and that bacterial proliferation can be induced following renal trauma. Activation of infection and bacterial proliferation did not always result in histopathologic damage to the kidney and was not associated with an increase in serum antibody.

Animals↗