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T Gray

Publications and source records attributed to T Gray.

At least 55 records · Page 3Linked to original sources
PubMed1996

Characterization of ocular hypertension induced by adenosine agonists.

PURPOSE: Previous studies have shown that adenosine agonists may induce a rise in intraocular pressure (IOP), a reduction in IOP, or both. Although the reduction in IOP results from the activation of adenosine A1 receptors, the mechanisms responsible for the rise in IOP have not been investigated. This study examines the receptors and mechanisms responsible for the adenosine agonist-induced rise in IOP. METHODS: The ocular effects of the nonselective adenosine agonist NECA, the relatively selective adenosine A2 agonist CV-1808, the A2a agonist CGS-21680, and the A1 agonist R-PIA were evaluated. RESULTS: The topical administration of CV-1808 produced a rapid rise in IOP, with a maximum increase of 15.6 +/- 1.6 mm Hg. Dose-response curves demonstrated that each agonist produced a dose-related rise in IOP with the following rank order of potency: NECA > CV-1808 > > R-PIA = CGS-21680. At times corresponding to the rise in IOP, the administration of high doses of CV-1808 (165 micrograms) produced a significant increase in aqueous humor flow and protein concentration. Increases in IOP and aqueous humor protein levels induced by CV-1808 were blocked by pretreatment with the adenosine A2 antagonist DMPX. In vitro studies demonstrated that CV-1808 did not alter cyclic adenosine monophosphate production in the rabbit iris-ciliary body. In cats, topical administration of CV-1808 produced a rapid rise in IOP, with a maximum increase of 8.1 +/- 2.4 mm Hg and an ED50 of 73 +/- 2.9 micrograms. This rise in IOP was blocked by DMPX pretreatment. CONCLUSIONS: These data demonstrate that adenosine receptor agonists can induce an acute rise in IOP in rabbits and cats. On the basis of pharmacologic characteristics, the rise in IOP is consistent with the activation of ocular adenosine A2 receptors. Functional studies indicate that at high doses, this rise in IOP involves an increase in aqueous flow and the breakdown of the blood-aqueous barrier.

Adenosine↗
PubMed1995

Regional variations of urokinase-type plasminogen activator in human colorectal cancer: a quantitative study by image analysis.

Qualitative histological studies in the distribution of urokinase-type plasminogen activator (uPA) in human colorectal carcinomas have been well documented. However, to our knowledge the histological distribution of this enzyme has not been quantified in any tumour. For the present image analysis study, uPA was demonstrated in sections of human colorectal cancer using immunoperoxidase technique. A total of 9 colorectal carcinoma cases were used, in which 132 regions were analysed. Within each region, staining intensity measurements were made at evenly spaced intervals. Samples of normal mucosa from 6 cases were also studied. Enzyme levels were assessed with staining intensity measurements. For each section, a negative control section was included, in which the primary antibody was omitted. Staining for uPA was quantified for each region in the test section, and the measurement for the corresponding region of the negative control was then subtracted. The enzyme uPA was localised more at the tumour edge than in the tumour centre or distant host tissue. These differences were highly significant (p < 0.0001). There was also a highly significant difference in staining intensity when tumour regions adjacent to pushing edge were compared with those adjacent to infiltrating edge (p < 0.0001). Infiltrating tumours showed stronger staining for uPA than tumours with pushing edges. Since invasive activity is thought to be maximal at the edge of the tumour, localisation of uPA at this site is consistent with the role of this enzyme in the process of tumour invasion.

Adenocarcinoma↗
PubMed1995

How to measure and predict the molar absorption coefficient of a protein.

The molar absorption coefficient, epsilon, of a protein is usually based on concentrations measured by dry weight, nitrogen, or amino acid analysis. The studies reported here suggest that the Edelhoch method is the best method for measuring epsilon for a protein. (This method is described by Gill and von Hippel [1989, Anal Biochem 182:319-326] and is based on data from Edelhoch [1967, Biochemistry 6:1948-1954]). The absorbance of a protein at 280 nm depends on the content of Trp, Tyr, and cystine (disulfide bonds). The average epsilon values for these chromophores in a sample of 18 well-characterized proteins have been estimated, and the epsilon values in water, propanol, 6 M guanidine hydrochloride (GdnHCl), and 8 M urea have been measured. For Trp, the average epsilon values for the proteins are less than the epsilon values measured in any of the solvents. For Tyr, the average epsilon values for the proteins are intermediate between those measured in 6 M GdnHCl and those measured in propanol. Based on a sample of 116 measured epsilon values for 80 proteins, the epsilon at 280 nm of a folded protein in water, epsilon (280), can best be predicted with this equation: epsilon (280) (M-1 cm-1) = (#Trp)(5,500) + (#Tyr)(1,490) + (#cystine)(125) These epsilon (280) values are quite reliable for proteins containing Trp residues, and less reliable for proteins that do not. However, the Edelhoch method is convenient and accurate, and the best approach is to measure rather than predict epsilon.

1-Propanol↗
PubMed1995

The extensor tendons to the little finger: an anatomic study.

Fifty cadaver hands were dissected to better delineate the extensor tendon anatomy to the little finger. The extensor digitorum communis was present in 35. Of 15 hands without an extensor digitorum communis, 12 had a junctura present. Three hands lacked both extensor digitorum communis and juncturae. Transfer of the extensor digiti minimi tendon in these hands could cause loss of extension to the little finger. Ten hands had a direct attachment of the extensor digiti minimi tendon on the abductor tubercle. Twenty-two hands had either an attachment of the extensor digiti minimi on the abductor tubercle, an unbalanced ulnar slip of the extensor digiti minimi, or both, anatomic factors that could--in the event of ulnar nerve compression or laceration--cause Wartenberg's sign. Twenty-eight hands did not have an anatomic variant of the extensor that could cause ulnar deviation of the little finger.

Cadaver↗
PubMed1995

Evidence for a weak angiogenic response to human colorectal cancers.

Many previous qualitative studies have shown that tumours are less vascular in the centre, and that host tissues become more vascular in close proximity to tumours. However, quantitative findings presented here for human colorectal cancer reveal some significant differences. Sections from 20 colorectal carcinomas (ten moderately and ten poorly differentiated) were immunostained with the QB/end/10 monoclonal to demonstrate blood vessels. These were measured by interactive morphometry and vascular volume density, surface density (Sv) and length density were recorded. In poorly differentiated carcinomas, the tumour centre was significantly less vascular than the periphery for all three parameters (P = 0.008 for Sv). However, no significant difference was seen for moderately differentiated tumours, which constitute the majority of colorectal cancers. Surrounding host tissues did not show a general increase in vascular density close to tumours. Furthermore, when total viable tissue was considered, the vascular density of carcinomas was not markedly different from normal mucosa. In the centre of moderately differentiated carcinomas for example, the mean value for Sv was only 1.4 times higher than the mean value for normal mucosa. These findings suggest that colorectal cancers may elicit a relatively weak angiogenic response, consistent with their exceptionally slow growth rate.

Animals↗
PubMed1995

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗
PubMed1995

The cortical neuritic pathology of Huntington's disease.

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Evidence for chromium acting as an essential trace element in insulin-dependent glucose uptake in cultured mouse myotubes.

Previous work from this and other laboratories has suggested that the trace element chromium plays some role in glucose homeostasis. In this study, we sought to characterise an in vitro cell culture model in which the effects of chromium on insulin-dependent glucose uptake could be studied. Mouse C2C12 myoblasts were differentiated to form myotubes in culture in chromium-replete or chromium-poor media. Chromium levels in standard media were 0.56 +/- 0.01 micrograms/l (mean +/- S.E.M.) compared with 0.09 +/- 0.01 micrograms/l in chromium-poor media. In chromium-poor media, insulin-stimulated uptake of radiolabelled glucose was reduced by almost 50% compared with that found in chromium-replete media. This decreased response could be restored by the addition of physiologically relevant (0.3 micrograms/l) concentrations of inorganic chromium (P < 0.001). The sensitivity of these cells to insulin was reduced dramatically by a reduction in the chromium content of the medium and was again increased (P < 0.001) by chromium addition. The concentrations of chromium required to restore the sensitivity to insulin were of the same order as those found physiologically; much higher concentrations of chromium could also stimulate glucose uptake in the absence of insulin but such concentrations were supra-physiological.

Animals↗
PubMed1994

Differential phylogenetic footprinting as a means to identify base changes responsible for recruitment of the anthropoid gamma gene to a fetal expression pattern.

Expression of the anthropoid (simian) gamma gene in fetal life contrasts with the exclusively embryonic expression pattern of the gamma-like genes of other eutherian mammals. To elucidate the factors responsible for this change in expression pattern, we utilized a strategy called differential phylogenetic footprinting (DPF). This strategy entails the following: (a) identification, within regulatory regions, of the gamma promoter, of individual nucleotides that differ between human (fetal expression), and galago (embryonic expression) gamma genes, (b) analysis of the effect of these nucleotide differences on the binding of nuclear proteins to human and galago sequences, and (c) assessment of the functional consequences of these binding changes in expression assays. The DPF analysis revealed several proteins that bind upstream from the CCAAT motif in the galago gamma promoter but do not bind to the corresponding region of the human gamma promoter. In transfection assays, binding of these proteins is associated with erythroid-specific repression of promoter strength. Binding sites for these proteins also occur near the CCAAT box of other embryonically expressed genes, including rabbit, mouse, and dwarf lemur gamma genes and the human epsilon globin gene. These data are consistent with the hypothesis that sequence changes near the proximal CCAAT box in the ancestral simian gamma gene may have facilitated a novel expression pattern by reducing the binding of repressors that act in the fetal stage.

Animals↗
PubMed1994

Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes.

The concept of steric stabilization as used in colloid science is applied to carefully manipulate the drainage and lymphatic distribution of subcutaneously administered model polystyrene nanospheres. A wide range of synthetic polyoxyethylene (POE)/polyoxypropylene (POP) block co-polymers of poloxamine and poloxamer series have been used to produce sterically stabilized nanospheres. We have found a correlation between the length of the stabilizing POE chains of the block co-polymers and nanosphere drainage and passageway across tissue lymph interface in dermal lymphatic capillaries in the rat footpads; the longer the POE chains, the faster the particle drainage. Nanospheres conditioned with block co-polymers of POE chains of 5-15 ethylene oxide units are effectively opsonized in lymphatics; a process which dramatically enhances sequestration (up to 40% of the administered dose) by macrophages of the regional lymph nodes. If the dimensions of the stabilizing POE chains of the poloxamines and poloxamers exceed the range of the Van der Waals force of attraction, opsonization fails to occur and rapidly drained engineered vehicles escape clearance by macrophages of the regional nodes, reach the systemic circulation and remain in the blood for prolonged periods. These observations suggest that a lymphatic delivery composition based on polymer-coated particles will be advantageous for many applications in clinical and experimental medicine.

Animals↗
PubMed1994

Modulation of intraocular pressure by adenosine agonists.

Adenosine receptors have been shown to modulate a variety of physiological functions; however, little is known about the role these receptors play in the modulation of ocular function. To investigate the potential role of adenosine receptors in modulating intraocular pressure (IOP), the A1 agonist N6-cyclopentyladenosine (CPA), the nonselective adenosine agonist 5'-N-ethylcarboxamideadenosine (NECA) and the A2 agonist 8-phenylaminoadenosine (CV-1808) were evaluated. Topical administration of NECA produced a dose-related reduction in IOP. However, an initial ocular hypertension of 1 to 2 hours was also observed in rabbits treated with NECA. The administration of CPA (165 micrograms) resulted only in a reduction in IOP, while the administration of CV-1808 produced only an initial ocular hypertension. As adenosine A1 receptors have been shown to be negatively coupled to adenylate cyclase in several systems, CPA was evaluated for its ability to suppress cAMP formation in the isolated iris/ciliary body. CPA produced a dose-related suppression of cAMP accumulation induced by 10(-6) M forskolin (EC50 = 3.2 nM). These results indicate that selected adenosine agonists can modulate IOP. The ocular hypotension induced by adenosine agonists is consistent with the activation of adenosine A1 receptors and may involve the modulation of cAMP levels in the iris/ciliary body.

Adenosine↗
PubMed1993

Alzheimer's disease: nursing interventions for clients and caretakers.

1. Senile dementia Alzheimer's type (SDAT), a progressive, degenerative disorder, affects tissues of the brain, causing a loss of neurons. This process results in brain atrophy, specifically in the frontal and temporal regions where integration of new information and memory retrieval occur. 2. Increasing age is the single most well-established risk factor for the development of SDAT (Brody, 1989). Because increasing age is the primary risk factor for the development of SDAT and because the elder population is increasing, the number of afflicted persons will probably rise (Ham, 1990). 3. The objectives of nursing interventions are to assist the client in remaining as independent as possible; to function at the highest possible cognitive, physical, emotional, and social levels; and to support the family and/or significant others in effectively carrying out their functions and goals.

Activities of Daily Living↗
PubMed1992

Apparent fusion of basement membranes in colorectal carcinoma.

Previous studies on colorectal carcinomas indicate that consistent differences in epithelial basement membrane (EBM) integrity are present between the tumour centre and periphery. We report that within the tumour centre, EBM staining between back-to-back (BTB) neoplastic glands (i.e., adjacent glands in direct contact with no intervening connective tissue) generally follows a pattern different from that of EBM staining at the tumour:stromal interface (TSI). Such distinctions are important, since the factors responsible for EBM deficiencies may vary with intra-tumoural location, as may the prognostic significance of these deficiencies. Analysis of paraffin sections from 130 colorectal carcinoma cases showed that EBM staining between BTB glands is generally weaker and more discontinuous than at the TSI, sometimes appearing as a linear array of immunostained granules on high-resolution light microscopy. By double-labelling immunofluorescence analysis of cryostat sections from 30 cases, a decrease in type-IV collagen:laminin staining intensity ratio was found between BTB glands. Hence, the composition of EBM between BTB glands appears to be abnormal. As much recent evidence indicates that epithelial:mesenchymal interactions play an essential role in EBM formation, the demonstration of immunostained EBM fragments between BTB glands requires an explanation: We suggest that the synthesis of EBM between BTB glands involved previously intervening stromal (mesenchymal) cells, and that EBM fusion and dissolution occur between BTB glands following the displacement of these cells.

Basement Membrane↗
PubMed1992

Changes in responsiveness of rat tracheal epithelial cells to transforming growth factor-beta 1 with time in culture.

Primary rat tracheal epithelial (RTE) cell cultures have previously been shown to be highly sensitive to growth inhibition by transforming growth factor-beta 1 (TGF beta 1) when treated within 1-2 days after plating. The purpose of the present studies was to examine the effects of TGF beta 1 on the growth of RTE cells as a function of time in culture. We found that the sensitivity of RTE cells to growth inhibition by TGF beta 1 decreased dramatically as the cultures aged. The IC50 for inhibition of colony forming efficiency was 0.18 pM when TGF beta 1 was added 24 h after cell plating. When TGF beta 1 treatment was begun on day 5 of culture, the IC50 was 3-4 pM as measured by inhibition of growth (cell number) and DNA synthesis. However, when TGF beta 1 was begun on day 19, the IC50 was 65 pM or greater than 500 pM, depending on whether inhibition of growth or DNA synthesis, respectively, was measured. TGF beta 1 accelerated cell death, as measured by exfoliation of cells, and inhibited cell proliferation. The decrease in responsiveness to TGF beta 1 in late cultures was shown to be dependent on culture age as well as on cell density. No evidence was found for inactivation or degradation of the added TGF beta 1 by the late stage cultures. Cells subcultured from late stage primary cultures remained less responsive to TGF beta 1 than subcultured cells from early cultures. Similar to its effect on proliferation, TGF beta 1 down-regulated the expression of two proliferation-related genes, c-myc and transforming growth factor-alpha, in early but not late RTE cell cultures. On the other hand, fibronectin expression was increased by TGF beta 1 by about twofold at both early and late times in culture. This indicates that the changes in TGF beta 1 responsiveness with time in culture are selective, apparently affecting primarily proliferation-related events.

Animals↗
PubMed1992

Fatal basilar vasculopathy complicating bacterial meningitis.

BACKGROUND: Bacterial meningitis complicated by thrombosis, vasculitis, and aneurysm formation affecting both small and distal branches of cerebral vessels has been well described. Involvement of major cerebral vessels is rare and has only been documented late in the course of disease. CASE DESCRIPTION: We describe the clinical and pathological findings in a young man who presented with pontine infarction as an early manifestation of bacterial meningitis. Streptococcus milleri, an unusual organism in this setting, was cultured. Despite improvement with antibiotic therapy, the patient experienced fatal subarachnoid hemorrhage. A ruptured inflammatory aneurysm of the basilar artery, evidence of residual meningitis and vasculitis, and basilar thrombosis associated with pontine infarction were found. CONCLUSIONS: Bacterial meningitis, which may be associated with severe vasculopathy of the basilar artery and lead to cerebral infarction, aneurysm formation, and subarachnoid hemorrhage, should be considered in the differential diagnosis of these conditions. The role of S. milleri in meningitis and its vascular complications merits further study.

Adult↗
PubMed1991

Persistent karyomegaly caused by Penicillium nephrotoxins in the rat.

Continuous or intermittent consumption by rats of food moulded by Penicillium aurantiogriseum induced prominent and extensive histopathological changes within several weeks seen specifically at the renal cortico-medullary junction. Many cells of the P3 segment of proximal tubules contained either giant nuclei or multiple enlarged nuclei, described in this text as karyomegaly, but also included within a cytomegalic change. The changes contrasted with the tubular cell necrosis and concomitant mitosis elicited after only four days consumption of nephrotoxic mould. Unilateral nephrectomy enabled persistence of histopathological changes to be assessed directly after detailed histology at an earlier stage. After ten days consumption of food with a 100-fold excess of fungal extract containing the amphoteric nephrotoxins, the typical acute histopathology evolved, over a period of three weeks on normal diet, into the bizarre karyomegalic histopathology, implying a latent effect. Karyomegaly persisted for at least twelve months after nephrotoxin dosage ceased. P. aurantiogriseum karyomegaly was much more striking than that induced by a relatively high chronic dose of another Penicillium nephrotoxin, ochratoxin A. Although the study does not attempt to measure relative potencies, qualitatively similar ultrastructural changes (enlarged nuclei, proliferation of smooth endoplasmic reticulum and thickening of proximal tubule basement membranes) were induced by the two types of nephrotoxin. The broadly toxic ochratoxin A is the popular putative aetiological agent in the mysterious and insidious Balkan endemic nephropathy and associated urinary tract tumours. As the renal carcinogenicity of ochratoxin A in rats follows karyomegaly, the striking karyomegaly induced by P. aurantiogriseum in the proximal tubules of the kidney must be considered as a potential factor in human chronic renal disease.

Animal Feed↗
PubMed1991

Critical variables controlling cell proliferation in primary cultures of rat tracheal epithelial cells.

The purpose of our experiments was to examine variables affecting early events in the establishment of rat tracheal epithelial (RTE) cultures as well as factors regulating long-term RTE cell growth. The experiments showed that when RTE cells were seeded into complete serum-free medium between 13 and 30% of the seeded cells attached. Of the seeded cells, only approximately 2% entered into DNA synthesis and underwent repeated cell divisions to form colonies containing greater than 20 cells. Coating the dishes with extracellular matrix components had little effect on cell attachment or colony forming efficiency (CFE). However, coating the dishes with fetal bovine serum markedly increased CFE. The media components bovine serum albumin and bovine pituitary extract were shown to be important in promoting cell attachment as well as CFE. Cholera toxin on the other hand had no effect on cell attachment but significantly increased CFE. These and other studies showed that cell attachment and cell proliferation are independently regulated. Studies on long-term culture growth indicated that the number of progeny produced per colony forming unit (CFU) is inversely proportional to the number of CFUs seeded. Inasmuch as the cultures did not become confluent under any of the culture conditions tested and media obtained from high density cultures were shown to be growth inhibitory, these findings suggest that a diffusible growth restraining factor is being produced by the cultures limiting clonal expansion. Experiments showing growth inhibitory effects of media conditioned by high cell density cultures support this interpretation. The putative factor reaches critical concentrations earlier in cultures seeded with high numbers of CFU than in cultures seeded with low numbers of CFU. Because the cultures are known to produce transforming growth factor-beta, this growth regulator probably plays a role in controlling RTE cell proliferation. However, it is likely than other events, such as depletion of growth factors from the media, also are significant in regulating the growth of the cultures.

Animals↗