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Biomedical subjects

J J Davis

Publications and source records attributed to J J Davis.

At least 19 recordsLinked to original sources
PubMed2005

Oncolytic virotherapy for cancer treatment: challenges and solutions.

Advances in gene modification and viral therapy have led to the development of a variety of vectors in several viral families that are capable of replication specifically in tumor cells. Because of the nature of viral delivery, infection, and replication, this technology, oncolytic virotherapy, may prove valuable for treating cancer patients, especially those with inoperable tumors. Current limitations exist, however, for oncolytic virotherapy. They include the body's B and T cell responses, innate inflammatory reactions, host range, safety risks involved in using modified viruses as treatments, and the requirement that most currently available oncolytic viruses require local administration. Another important constraint is that genetically enhanced vectors may or may not adhere to their replication restrictions in long-term applications. Several solutions and strategies already exist, however, to minimize or circumvent many of these limitations, supporting viral oncolytic therapy as a viable option and powerful tool in the fight against cancer.

Animals↗
PubMed2005

JNK1-dependent antimitotic activity of thiazolidin compounds in human non-small-cell lung and colon cancer cells.

We recently identified two thiazolidin compounds, 5-[(4-methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone (MMPT) and 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), that inhibit the growth of human non-small-cell lung and colon cancer cells independent of P-glycoprotein and p53 status. Here we further investigated the mechanism by which these thiazolidin compounds mediate their anticancer effects. Treatment of cancer cells with MMPT and DBPT led to a time-dependent accumulation of cells arrested in the G2/M phase with modulation of the expression of proteins such as cyclin B1, cdc25C, and phosphorylated histone H3. Moreover, treatment with MMPT and DBPT increased M-phase arrest with abnormal spindle formation. DBPT-mediated G2/M phase arrest and phosphorylation of cdc25C and histone H3 were abrogated when JNK activation was blocked either with SP600125, a specific JNK inhibitor, or a dominant-negative JNK1 gene. Moreover, DBPT-mediated microtubule disruption was also blocked by SP600125 treatment. Our results demonstrate that thiazolidin compounds can effectively induce G2/M arrest in cancer cells and that this G2/M arrest requires JNK activation.

Aniline Compounds↗
PubMed2003

Molecular bioelectronics.

Biological macromolecules have evolved over many millions of years into structures primed, in some cases, for both specific surface recognition and facile, directional electron tunnelling. The redox-active centres of metalloproteins play a central role in photosynthesis and respiration. The processes by which constructive man-made interfaces to these moieties can be generated have advanced greatly during the past two decades or so. Together with recent advances in molecular manipulation, analyses and lithographic fabrication, this knowledge has led to us to the point where bioelectronic devices can be designed and interrogated with good levels of reproducibility.

Biopolymers↗
PubMed2001

High resolution scanning force microscopy of cardiac myocytes.

The advent of scanning probe microscopy has introduced a powerful new method of probing the structural features of biological specimens. In this study, high resolution atomic force microscopy micrographs of single, isolated, cardiac myocytes are presented. Significantly, our images show not only the features to be expected of the external sarcolemma, but also resolve sub-surface features, including the striated pattern of the contractile proteins and their associated sarcoplasmic reticulum and mitochondria.

Animals↗
PubMed2000

Ultrastructural organization of amyloid fibrils by atomic force microscopy.

Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR(10-19) fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.

Amyloid↗
PubMed2000

A scanning tunnelling microscopy study of Clostridium pasteurianum rubredoxin.

Scanning tunnelling microscopy (STM), which can provide 'direct' and 'non-averaged' information on molecular structure in three dimensions, has been used to achieve sub-molecular resolution in a 'single molecule' of rubredoxin, an important iron-sulphur protein, at the gold (111)/water interface. The metal-ligand site [Fe(III)-Cys4] appears distinct because of an enhancement of the tunnelling current over this region compared to the surrounding protein structure.

Clostridium↗
PubMed2000

A scanning tunnelling study of immobilised cytochrome P450cam.

A site-specifically engineered surface cysteine residue, located in a region where the haem moiety is closest to the surface, is used to anchor cytochrome P450cam enzyme molecules covalently to a gold electrode. More reproducibly ordered adsorption, at high coverage, occurs with this K344C mutant than with the wild-type enzyme. The subsequently formed close-packed monolayer arrays have been probed by scanning tunnelling microscopy under ambient conditions and under aqueous (buffered) solution at high resolution. Initial indications suggest that the immobilised enzyme is both electrochemically addressable and catalytically active.

Camphor 5-Monooxygenase↗
PubMed1999

The effect of bovine somatotropin treatment on production of lactating angora does with kids.

Fourteen Angora does (35+/-2 kg), each with a single kid and in the first month of lactation, were used to determine ongoing (Period 1) and residual (Period 2) effects of chronic bovine somatotropin (bST) treatment. Specifically, we sought to determine whether chronic bST treatment was capable of improving milk yield, and thus kid growth, and mohair production of nursing does. The experiment consisted of a 2-wk pretreatment period, 5 wk of weekly subcutaneous treatment of slow-release bST (n = 7; Period 1), and a 4-wk posttreatment period (Period 2). The weekly dose of bST was calculated to release 100 microg/(kg BW.d(-1)). To estimate milk production, kids were separated from the does daily for 5 h, and their BW was recorded before and after suckling. The difference in BW was taken as milk production for 5 h. Fiber growth was measured by shearing does at the start of the experiment and at the end of Periods 1 and 2. Dry matter intake and BW of does were not affected by bST (P>.05). Average daily gain of kids that were suckling bST-treated does was higher (P<.05) than for kids of untreated does during Period 1 (184 vs. 139 g/d) but not during Period 2 (140 vs. 136 g/d; P>.10). Treatment with bST did not affect (P>.10) milk composition or clean fleece production in either period. Injection of bST did not affect (P>.10) plasma concentrations of glucose (mean = 49.5 mg/dL), urea N (mean = 19 mg/dL), total protein (mean = 72.5 g/d), or NEFA (mean = 122 microEq/L). During the period of bST treatment, plasma concentrations of somatotropin and IGF-I were increased (P<.05), concentrations of thyroxine and cortisol were decreased (P<.10), and plasma insulin levels were unchanged (P>.10) by bST. In conclusion, treatment of Angora dams with bST did not change DMI or mohair growth, but it improved growth of their kids.

Animals↗
PubMed1999

Effects of bovine somatotropin and ruminally undegraded protein on feed intake, live weight gain, and mohair production by yearling Angora wethers.

Yearling Angora wethers (n = 24; 24+/-1.0 kg BW) were used in an experiment with a 2 x 2 factorial arrangement of treatments to investigate effects of bovine somatotropin (bST) treatment and dietary level of ruminally undegraded protein on DMI, ADG, and mohair production. Untreated casein (UC) or casein treated with formaldehyde (TC) was included at 7% DM of a diet containing 11% CP and 46% concentrate. A slow-release bST form was administered weekly to deliver 0 (Control) or 100 microg/ (kg BW.d) of bST. Plasma concentrations of bST and IGF-I were increased (P < .05) during the 7-d period following bST injection. Ruminal fluid ammonia N concentration was lower (P < .01) for TC than for UC before feeding (6.6 vs 7.5 mg/dL) and 4 h later (8.2 vs 12.2 mg/dL), and total VFA concentration was lower (P < .01) for TC than for UC. Treatment with bST decreased (P = .08) DMI with UC (1.15 vs .91 kg/d) and increased (P = .08) DMI with TC (.95 vs 1.06 kg/d). Formaldehyde treatment of casein increased ADG (65, 74, 55, and 91 g/d; P = .03) and clean fleece production (P < .01; 14.1, 17.3, 15.0, and 18.4 g/d for UC-Control, TC-Control, UC-bST, and TC-bST, respectively), with no effect of bST during the 8-wk period of treatment or for the 8 wk thereafter (P > .10). In conclusion, with yearling Angora wethers, bST does not seem useful to enhance mohair production and may not alter effects of dietary level of ruminally undegradable protein on mohair production.

Amino Acids↗
PubMed1999

Achilles tendon ruptures stratified by age, race, and cause of injury among active duty U.S. Military members.

A total of 865 members of the U.S. military underwent repair of Achilles tendon ruptures at U.S. military hospitals during calendar years 1994, 1995, and 1996. The discharge summaries of these patients were analyzed for patient demographic information, including age, race, and causative activity. Patients were then stratified by age, race, and cause of injury. Blacks were at increased risk for undergoing repair of the Achilles tendon compared with nonblacks (overall relative risk = 4.15, 95% confidence interval [CI] = 3.63, 4.74; summary odds ratio controlling for age = 3.69, CI = 3.25, 4.19). Participation in the game of basketball accounted for 64.9% of all injuries in black patients and 34.0% of all injuries in nonblack patients. Among those injured, blacks had a significantly increased risk for injury related to playing basketball than nonblacks (relative risk = 1.82, CI = 1.58, 2.10). This finding suggests that there may be other predisposing factor(s) that result in a higher risk of Achilles tendon ruptures in black individuals.

Achilles Tendon↗
PubMed1996

Determination of mimosine and 3,4-dihydroxypyridine in milk and plasma of goats.

A simple method for determination of mimosine and 3,4-dihydroxypyridine (3,4-DHP) in plasma and milk was developed. Milk and plasma, with tyrosine as internal standard, were deproteinized using 9% trichloracetic acid and extracted with diethyl ether. Metabolites were separated by isocratic high-performance liquid chromatography, with 0.02 M orthophosphoric acid (pH 2.5) at 0.5 ml/min and a Hypersil ODS microbore column. Mimosine, 3,4-DHP and tyrosine were detected at 275 nm. The recovery of the mimosine added to the plasma samples was 101.6 +/- 2.3% and 103.3 +/- 1.0% for milk samples. 3,4-DHP recovery for plasma samples was 101.2 +/- 0.9% and for milk samples 100.8 +/- 1.4%. The reproducibility of the method was evaluated by analyzing six plasma samples and six goat milk samples. The analyses yielded relative standard deviations of 2.65 and 2.82%, respectively.

Animals↗
PubMed1995

Paint as a source of recontamination of houses in urban environments and its role in maintaining elevated blood leads in children.

A detailed lead isotopic and scanning electron microscope investigation of particulates from three houses in urban Sydney, previously decontaminated by their owners, has shown that they have been recontaminated over varying periods, as short as 6 months. The source of recontamination is lead paint from adjoining dwellings whose paint is thoroughly deteriorated, as well as from unknown sources. In one house, the external to internal lead loading was > 10:1. The pathway for the lead paint contaminants is both airborne and mechanical transport into the houses. Recontamination of houses provides an explanation for the maintenance of elevated blood lead levels in the children residing in these houses. Recontamination can be a major urban problem applicable in any community which used leaded paints on dwellings in the past. It is a matter of concern for families with young children and couples, especially women who are, or intend to become, pregnant.

Air Pollutants↗
PubMed1995

Technical note: tissue residues of mimosine and 2,3-dihydroxypyridine after intravenous infusion in goats.

Sixteen growing Alpine wethers (average BW 35 +/- 2 kg) were assigned to one of four treatments to evaluate tissue retention of the leucaena toxins mimosine (MIM) and 2,3-dihydroxypyridine (2,3-DHP). Treatments were infused i.v. for 2 d and were 1) saline control, 2) MIM (200 mg.kg BW-.75.d-1), 3) 2,3-DHP (200 mg.kg BW-.75.d-1), or 4) MIM (100 mg.kg BW-.75.d-1) + 2,3-DHP (100 mg.kg BW-.75.d-1). Immediately after the infusion, the goats were slaughtered and tissue concentrations of MIM and 2,3-DHP were determined via HPLC. No detectable levels of either toxin were found in spleen, heart, lung, or muscle; however, appreciable amounts of MIM and 2,3-DHP were found in plasma, kidney, and liver samples. Kidney MIM content was greater (P < .01) than that of liver, although liver tended to retain slightly more 2,3-DHP (P > .05). Infusion of MIM resulted in a plasma MIM content of 39 to 54 mumol/L and reduced (P < .01) plasma PHE and LEU. Infusion of 2,3-DHP resulted in a plasma 2,3-DHP content of 9.4 mumol/L and increased plasma THR, ARG, VAL, PHE, ILE, LEU, and LYS concentrations (P < .10). Humans consuming offals from ruminants consuming large amounts of the leguminous forage leucaena may be exposed to appreciable quantities of MIM and 2,3-DHP.

Animals↗
PubMed1989

Modification of the silver impregnation technique of Bielschowsky for use in glycol methacrylate-embedded brain tissue.

The modified Bielschowsky stain has become the standard silver impregnation technique for use in paraffin-embedded tissue sections for identifying abnormalities of neuritic processes in a variety of neurodegenerative disorders such as Alzheimer's disease. Recently, glycol methacrylate embedding has been used increasingly as a substitute for paraffin embedding of tissue, because it results in less tissue distortion during processing and provides greater clarity and resolution of cellular architecture and structural details. We have been able to modify the Bielschowsky stain for use in glycol methacrylate-embedded brain sections. The use of this technique will permit more accurate quantitation of the histopathologic changes in neuritic processes in neurodegenerative diseases.

Acrylates↗