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Biomedical subjects

D G Jackson

Publications and source records attributed to D G Jackson.

66 records · Page 4Linked to original sources
PubMed1990

Diminished beta-adrenergic receptor responsiveness and cardiac dilation in hearts of myopathic Syrian hamsters (BIO 53.58) are associated with a functional abnormality of the G stimulatory protein.

Previous studies have demonstrated a diminution in the bioactivity of the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase (Gs) in hearts of the hypertrophic BIO 14.6 Syrian hamster. In this study, we measured functional activity and immunodetectable levels of Gs in a mutant strain of hamsters (BIO 53.58) that develop a dilated cardiomyopathy. Pathological studies demonstrated that 100-day-old BIO 53.58 hamsters had substantial ventricular dilation when compared with age-matched F1B controls. Additionally, these 100-day-old hamsters demonstrated diminished contractile response to beta-adrenergic receptor stimulation. The pathological and hemodynamic changes were associated with defective coupling of Gs to adenylyl cyclase as adenylyl cyclase activation was distinctly decreased in the presence of isoproterenol, fluoride ion, guanine nucleotides, and forskolin. Additionally, the ability of the alpha-subunit of Gs to reconstitute isoproterenol-stimulated adenylyl cyclase activity in S49 cyc- membranes was reduced approximately 65%. By contrast, cyc- complementation assays did not reveal a difference between the functional activity of Gs in hearts from 30-day-old BIO 53.58 hamsters and F1B controls. Furthermore, beta-adrenergic receptor stimulation of adenylyl cyclase in the membranes of the young BIO 53.58 hamsters was not significantly different from controls. The substantial alterations in Gs bioactivity in hearts of the 100-day-old BIO 53.58 hamsters was not associated with alterations in the immunodetectable levels of either alpha Gs or alpha Gi on Western Blots. These results suggest that G protein changes are associated with ventricular dilation in BIO 53.58 hamsters and that G protein levels are not always reflective of G protein bioactivity.

Adenylyl Cyclases↗
PubMed1986

Reaction of neutral endopeptidase 24.11 (enkephalinase) with arginine reagents.

The effect of the arginine-specific reagents phenylglyoxal and butanedione on the activity of neutral endopeptidase 24.11 ("enkephalinase") was determined. Inactivation of the enzyme by butanedione is completely protected by methionine-enkephalin, but only partially protected by methionine-enkephalinamide. In contrast, phenylglyoxal inactivation of the enzyme exhibits saturation kinetics with a Kd of 20 mM. The enzyme is only partially protected against phenylglyoxal inactivation by both methionine-enkephalin and its amide, indicating that phenylglyoxal reacts at two sites. Reaction of the enzyme with phenylglyoxal in the presence of saturating methionine-enkephalin involves the direct reaction of the reagent with the enzyme-substrate complex. Enzyme treated with butanedione or with phenylglyoxal (at site 1) exhibits a 3-5 decrease in substrate binding with little change in kcat. In contrast, reaction with phenylglyoxal in the presence of saturating methionine-enkephalin shows little change in substrate binding but a 4-fold decrease in kcat. Enzyme inactivation involves the incorporation of approximately 1 mol of phenylglyoxal/enzyme subunit in the absence of methionine-enkephalin and approximately 2.5 mol of phenylglyoxal/enzyme subunit in the presence of saturating methionine-enkephalin. These results suggest that an arginine residue on the enzyme is involved in substrate binding.

Aldehydes↗
PubMed1985

A new method for the rapid purification of both the membrane-bound and released forms of the variant surface glycoprotein from Trypanosoma brucei.

A simple new technique was developed for the rapid purification of either the membrane-bound or the released forms of the variant surface glycoprotein of Trypanosoma brucei in high yield. Whole cells were used as the source of the membrane-bound form, and the supernatant of benzyl alcohol-treated cells was used as the source of the released form. The technique was based on extraction of the acid-treated protein into chloroform/methanol, followed by selective re-partition into aqueous salt solution. The yield of purified protein was found to be dependent critically on a low pH during the extraction/re-partition stages. This finding and the ability to cycle the protein repeatedly through organic and aqueous phases in a strictly pH-dependent manner suggested that the protein could undergo fully reversible denaturation/renaturation only while in an extensively protonated form. The yield was independent of the polarity of the organic phase and the protein concentration over a wide range. After purification, both forms retain their ability to react with specific antibody raised against the authentic native protein purified by conventional means. The amino acid composition and the identity of the N-terminal amino acid was the same for both forms of the protein. In addition, both forms had blocked C-terminal residues. There were determined to be 1.13 X 10(7) copies of the variant surface glycoprotein per cell.

Amino Acids↗
PubMed1985

Release of the variable surface coat glycoprotein from Trypanosoma brucei requires the cleavage of a phosphate ester.

The membrane-bound and released forms of the variant surface coat glycoprotein from Trypanosoma brucei have been purified to homogeneity by a new rapid method in the absence of detergents. The conversion of the membrane-bound form to the released form has been found to consist of the cleavage of a phosphodiester bond, distal to the phosphate, linking the protein to a phospholipid. We suggest that this linkage constitutes the normal mode of attachment of the protein to the outer leaflet of the plasma membrane.

Animals↗
PubMed1984

An evaluation of the time-dependent dimensional stability of eleven elastomeric impression materials.

The dimensional stability of three polysulfides, one condensation-cured silicone, six addition-cured silicones, and one polyether, was evaluated when poured immediately and after storage for 1, 4, and 24 hours. Dimensional stability was determined by measuring the amount of gap width developed by a master coping when seated on the die that had been poured in the impression. The greatest accuracy occurred when the impressions were poured immediately. All the addition-cured silicone materials exhibited excellent dimensional stability for all storage times. Delayed pouring of artificial stone in the impressions made in these materials should result in very little change in die accuracy. The condensation-cured silicone material Polytrans has good accuracy if poured immediately. Delayed pouring results in a rapid loss of accuracy. The polysulfides have good accuracy only if poured immediately, with the exception of Omniflex, which can be stored up to 4 hours with only a minimum loss of accuracy. The polyether material Impregum expanded during storage. Since the dimensional change of the impression during storage is a characteristic of the material, a reduction in its bulk should lead to a desired amount of dimensional change. To achieve this desirable state, custom trays that will provide for the minimum recommended bulk of material should be fabricated. The complex geometry of the cavity preparation makes any prediction of the desirability of impression material expansion or contraction difficult, because a change in impression material dimensions may be beneficial to the fit in one portion of the casting but have an extremely adverse effect in another.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMedDate not supplied

Histopathological and ultrastructural changes in the juxtaglomerular apparatus of the rat following administration of ZENECA ZD6888 (2-ethyl-5,6,7,8-tetrahydro-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)- methoxy]quinoline), an angiotensin II antagonist.

Male and female Alderley Park rats were treated for 26 wk with ZENECA ZD6888, an angiotensin II (AII) antagonist, at doses of 25, 50, and 250 mg/kg/day and the kidneys examined by light and electron microscopy. Nephropathy (tubular degeneration and regeneration), thickening of the basal lamina, mononuclear cell infiltration, and hypertrophy and hyperplasia of the juxtaglomerular apparatus were seen by light microscopy. Ultrastructurally, juxtaglomerular cell granules were increased in number and displayed substantial structural heterogeneity. In some cells, granules contained paracrystalline inclusions while others consisted predominantly of myelinic debris. Evidence of conversion of arteriolar smooth muscle cells into juxtaglomerular cells and their degeneration was also obtained by electron microscopy. The juxtaglomerular changes were treatment- and dose-related and were attributed to an exaggerated pharmacological action of the compound, that is, ZD6888-mediated blockade of AII receptors leading to competitive inhibition of the AII-mediated release of renin. The resemblance between the findings seen in the present study following administration of an AII antagonist and those due to angiotensin-converting enzyme inhibitors reported by others was striking.

Angiotensin II↗
PubMedDate not supplied

The effects of ZENECA ZD8731, an angiotensin II antagonist, on renin expression by juxtaglomerular cells in the rat: comparison of protein and mRNA expression as detected by immunohistochemistry and in situ hybridization.

Changes in the mRNA and protein expression of renin-secreting cells in the juxtaglomerular apparatus (JGA) were examined in the rat following administration of ZENECA ZD8731, an angiotensin II receptor antagonist. Doses of 0 or 90 mg/kg were administered daily by gavage for 26 wk. JGA hypertrophy was apparent in histological sections. Immunohistochemistry demonstrated an increase in the number of renin-containing cells in both the afferent arterioles and the interlobular arteries. Similarly, renin mRNA expression, demonstrated by in situ hybridization, had extended to more proximal segments of the afferent arterioles and was also present in efferent arterioles and interlobular arteries. In conclusion, JGA hypertrophy occurred as a result of antagonism of the angiotensin II receptor. Associated with JGA hypertrophy was increased expression of both renin and renin mRNA, indicative of stimulated renin synthesis caused by an exaggerated pharmacological response of renin-secreting cells to the loss of feedback inhibition by angiotensin II.

Angiotensin II↗
PubMedDate not supplied

Fine morphology of the advancing front of cholesteatome--experimental and human.

The fine morphology of the advancing front of the cholesteatoma and the mucocutaneous juction of implanted skin in the feline bulla have been investigated. Inflammatory cell infiltration was frequently observed at the advancing front and the mucocutaneous junction. It is suggested that this frequent inflammation at this junction is due to the lack of a tight seal. In the advancing front, epidermal migrating cells appear to be lower spinous cells (or "suprabasalar" cells) rather than basal cells. It appears that the slender cell processes of the migrating cells make the initial attachment to the fibrin and/or basement membrane left behind by the degenerated epithelial cells as a result of inflammation and migrate along these structures, using them as a guide. Implanted skin in the cat's bulla failed to develop a pearl formation but frequently developed an epiboly, in which case the epidermis receded and was partly replaced by mucous membrane, and its stroma was heavily invaded by mucous epithelium, resembling tubular glands.

Animals↗
PubMedDate not supplied

New molecular markers for the study of tumour lymphangiogenesis.

The capacity of malignant tumours to metastasize to distant tissues presents a huge problem for the treatment of cancers using conventional surgical and cytotoxic drug therapies. One of the main routes for tumour spread is via the lymphatic vessels, an important conduit for tumours such as breast, lung and gastrointestinal tract that frequently colonize regional lymph nodes. In comparison with the vasculature however, little is known about the biology of tumour lymphatics, tumour lymphangiogenesis or the mechanisms that regulate entry and subsequent migration of tumour cells within lymphatic vessels. This situation has persisted because of the lack of specific molecular markers with which to visualize even normal lymphatics within tissues or to isolate lymphatic endothelial cells for in vitro experimental analysis. Just recently however, novel markers for lymphatic endothelial cells have been identified and their availability has revolutionized research in this field. In this article we highlight the main characteristics of these markers and review recent progress in their use to study tumour lymphangiogenesis.

Animals↗