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Biomedical subjects

D A Russell

Publications and source records attributed to D A Russell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Tissue-specific expression in transgenic maize of four endosperm promoters from maize and rice.

The tissue-specific, developmental, and genetic control of four endosperm-active genes was studied via expression of GUS reporter genes in transgenic maize plants. The transgenes included promoters from the maize granule-bound starch synthase (Waxy) gene (zmGBS), a maize 27 kDa zein gene (zmZ27), a rice small subunit ADP-glucose pyrophosphorylase gene (osAGP) and the rice glutelin 1 gene (osGT1). Most plants had a transgene expression profile similar to that of the endogenous gene: expression in the pollen and endosperm for the zmGBS transgene, and endosperm only for the others. Histological analysis indicated expression initiated at the periphery of the endosperm for zmGBS, zmZ27 and osGT1, while osAGP transgene activity tended to start in the lower portion of the seed. Transgene expression at the RNA level was proportional to GUS activity, and did not influence endogenous gene expression. Genetic analysis showed that there was a positive dosage response with most lines. Activity of the zmGBS transgene was threefold higher in a low starch (shrunken 2) genetic background. This effect was not seen with zmZ27 or osGTI transgenes. The expression of the transgenes is discussed relative to the known behaviour of the endogenous genes, and the developmental programme of the maize endosperm.

Blotting, Southern↗
PubMed1997

Excited state properties of the siderophore pyochelin and its complex with zinc ions.

The critical effects of pH on the electronic absorption and fluorescence characteristics of the siderophore, pyochelin, are investigated. A single anionic species is shown to be sufficient to explain the data obtained under alkaline conditions. In acidic solutions, several competing ground- and excited-state equilibria are present, which lead to fluorescence emissions from both the protonated form of pyochelin and its phenolate ion. From the spectroscopic data we are also able to show that pyochelin interacts with zinc ions in the ground state via its anionic form, thereby confirming that this siderophore does not bind Fe(III) ions uniquely.

Chromatography, High Pressure Liquid↗
PubMed1996

Peripheral administration of Interleukin-1 Receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat.

We assessed the efficacy of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain injury and edema formation after permanent middle cerebral artery occlusion (MCAo) in the rat. Previous studies showed that low amounts of rhIL-1ra injected directly into the brain significantly decreased infarct size after MCAo or excitotoxic injury in rats. Peripheral administration of rhIL-1ra (100 mg/kg sc at 0, 4, 8, 12, and 18 h after MCAo) significantly inhibited infarct size, by 46% (P < 0.05), measured at 24h. This was greater than the effect of MK801 administered immediately after MCAo (4 mg/kg ip, 0 h) which did not significantly reduce infarct size. rhIL-1ra (100 mg/kg also significantly inhibited cerebral edema formation by 49% (p< 0.05 measured 24 h after MCAo, but did not reduce edema formation measured 2 h after MCAo, but did not reduce edema formation measured 2 h after MCAo. Inhibition of infarction by rhIL-1ra was dependent on dose and time of administration. Together the results demonstrate that peripherally administered rhIL-1ra at high doses is able to mimic the efficacy of low dose of rhIL-1ra administered directly into the brain in a rodent model of stroke and that protection observed with rhIL-1ra was better than that offered by MK801 in this model.

Animals↗
PubMed1996

Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.

The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.

Administration, Oral↗
PubMed1996

Tumour-localising and -photosensitising properties of a novel zinc(II) octadecylphthalocyanine.

1,4,8,11,15,18,22,25-Octadecylphthalocyaninato zinc(II), ZnODPc, incorporated into a Cremophor emulsion, was assayed for its pharmacokinetic and phototherapeutic properties in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The phthalocyanine was injected intravenously (i.v.) in three doses, i.e. 1.46, 0.73 and 0.37 mumol kg-1 body weight. In all cases, the octadecyl-substituted phthalocyanine showed an unusually high affinity for serum low-density lipoproteins (LDLs) and a high efficiency and selectivity of tumour targeting: the maximum accumulation in the tumour occurred at 24 h after injection, whereas no detectable amount of phthalocyanine was recovered from the muscle, i.e. the peritumoral tissue, between 1 h and 1 week after injection. At the same time, low amounts of phthalocyanine were recovered from skin and then only at short times after injection, with skin photosensitivity rapidly disappearing and the phthalocyanine present in the serum only. Tumour photosensitisation studies were carried out at 24 h after administration of 1.46 mumol kg-1 ZnODPc and showed that this phthalocyanine has a very high phototherapeutic efficiency; this is probably a consequence of the multiple mechanisms by which the phthalocyanine induces tumour damage, involving both direct modification of malignant cells and impairment of blood flow, as well as the alteration of a variety of subcellular components, such as mitochondria, the rough endoplasmic reticulum, the perinuclear membrane and, occasionally, cell nuclei. Tumour necrosis appears to be the consequence of both random cell death and apoptosis.

Animals↗
PubMed1996

Calcium biosensing with a sol-gel immobilized photoprotein.

Aequorin, the bioluminescent protein found in the jellyfish Aequorea sp., has been immobilized in a porous sol-gel glass environment. The luminescence from this protein is specifically triggered by the presence of calcium ions, thus offering exciting possibilities for the development of an optical biosensor for this cationic species. The luminescence emission spectrum has been measured from the aequorin protein after interaction with calcium ions. The intensity of the luminescence, measured at the peak maximum of 470 nm, for the encapsulated protein has been calibrated against calcium ion concentration. The characterization of the protein within the sol-gel matrix has been reported together with biosensing experiments using human sera and milk samples. The results suggest that the sol-gel encapsulated aequorin protein offers potential as a one shot bioluminescence based biosensor for the determination of calcium ions in such complex matrices.

Biosensing Techniques↗
PubMed1996

Case report: ranitidine-induced bradycardia in a patient with dextrocardia.

Although rare, bradycardia and other cardiac arrhythmias have been associated with the use of H2-receptor antagonists. Ranitidine is among the most frequently prescribed drugs. In this article, the authors observed a ranitidine-mediated sinus bradycardia in a man with dextrocardia (situs inversus) who had acute bleeding from a duodenal ulcer. The bradycardia was resolved after ranitidine was discontinued.

Abdomen↗
PubMed1996

Cachectic effect of ciliary neurotrophic factor on innervated skeletal muscle.

Recombinant human ciliary neurotrophic factor (rh-CNTF) was reported to attenuate skeletal muscle wasting in rats after unilateral transection of the sciatic nerve (M. E. Helgren, S. P. Squinto, H. L. Davis, D. J. Parry, T. G. Bolton, C. S. Heck, Y. Zhu, G. D. Yancopoulos, R. M. Lindsay, and P. S. DiStefano. Cell 76: 493-504, 1994). Under the experimental conditions reported herein, the absolute masses of the denervated gastrocnemius and soleus muscles were not increased in mature or immature rats of either sex by treatment with rhCNTF. At the highest doses of rhCNTF (1 and 0.1 mg/kg), increases in the ratio of the masses of the denervated to the contralateral innervated gastrocnemius and soleus muscles could be attributed entirely to a muscle-wasting effect on the contralateral innervated muscle rather than any muscle-sparing effect on the denervated muscle. The muscle-wasting effects of rhCNTF were associated with reductions in body weight gain and reduced food intake. Pair-fed rats lost less body weight and skeletal muscle mass than rhCNTF-injected freely fed rats but experienced significantly greater loss of visceral mass. Male rats displayed greater loss of body weight and skeletal muscle mass than female rats. Recombinant inhibitors of the cachectic cytokines, tumor necrosis factor and interleukin-1, did not significantly alter the wasting effects of rhCNTF. These findings demonstrate that, in contrast to its well-characterized trophic effects on cells of the nervous system, rhCNTF causes atrophy of skeletal muscle by mechanisms involving both anorexia and cachexia based on the results of pair-feeding experiments.

Animals↗
PubMed1996

Endodontic therapy and surgical excision of a chronic suppurative osteomyelitic lesion in a horse: a case report.

A 22-year-old thoroughbred gelding was presented for evaluation and treatment of chronic dental disease. The horse had a history of quidding and abnormal bite behavior. Intraoral examination revealed signs of chronic generalized gingival inflammation and severe dental caries affecting the maxillary and mandibular incisor teeth. Treatment was provided on two separate visits over an interval of four months. The first visit consisted of the surgical extraction of three unrestorable incisor teeth and restoration of six carious maxillary incisor teeth. The second visit consisted of conventional endodontic therapy on the remaining mandibular incisor teeth and the surgical removal of a chronic suppurative osteomyelitic lesion. Immediate and long term improvements in eating habits were noted. Three month follow-up examinations following completion of treatment have shown the teeth to be in functional position, the restorations intact, and the surgical site well healed.

Animals↗
PubMed1995

A central role for IL-1 beta in the in vitro and in vivo regulation of hepatic inducible nitric oxide synthase. IL-1 beta induces hepatic nitric oxide synthesis.

We have previously demonstrated that high levels of inducible nitric oxide synthase (iNOS) expression in hepatocytes required a combination of LPS and TNF-alpha, IL-1 beta, and IFN-gamma. The need for such a complex regulatory system seemed unwarranted based on the importance of NO in the liver. Therefore, we investigated whether individual cytokines could induce NO synthesis in hepatocytes and characterized some of the mechanisms involved. Rat hepatocytes were stimulated in vitro with escalating doses of TNF-alpha, IL-1 beta, or IFN-gamma. Only IL-1 beta induced high levels of iNOS mRNA and corresponding NO2- + NO3- production, and dexamethasone and cycloheximide blocked a majority of this response. Nuclear run-on experiments revealed that IL-1 beta upregulated iNOS gene transcription. IL-1 receptor antagonist protein (IL-1ra) competitively inhibited IL-1 beta-stimulated NO synthesis, implying activation through a cell-specific receptor. Rats injected with both LPS and IL-1ra showed decreased hepatic iNOS mRNA and plasma NO2- + NO3- compared with rats given LPS alone, indicating that IL-1 beta plays a role in regulating iNOS expression within the liver in vivo during endotoxemia. The soluble TNF receptor antagonist, PEG-(rsTNF-RI)2, also suppressed hepatic iNOS mRNA levels and plasma NO2- + NO3- increases, supporting a role for this cytokine in LPS-induced iNOS expression. Finally, IL-1 beta at high doses also induced iNOS mRNA and significant NO2- + NO3- production in cultures of primary human hepatocytes. These data indicate an important role for IL-1 beta in the regulation of hepatic NO synthesis.

Animals↗
PubMed1995

Potent inhibitory effects of glial derived neurotrophic factor against kainic acid mediated seizures in the rat.

Recently messenger RNA (mRNA) for glial derived neurotrophic factor (GDNF), a recently discovered member of the TGF-beta superfamily, was shown to increase in the hippocampus after kainic acid-induced seizures. The possibility that exogenous recombinant human (rh) GDNF may have anticonvulsant properties was investigated using a model of temporal lobe epilepsy in the rat. rhGDNF, vehicle or inactive rhGDNF were injected intracerebroventricularly 1 h before peripheral administration of kainic acid. rhGDNF suppressed kainic acid-induced tonic-clonic convulsions when compared to animals treated with vehicle or inactive rhGDNF. The inhibition of kainic acid-induced seizure activity by rhGDNF also prevented the associated neuronal cell loss in hippocampal, thalamic and amygdaloid regions. These results suggest that rhGDNF should be evaluated in other seizure and acute neural disorders that are associated with excitotoxic processes.

Adrenergic Fibers↗
PubMed1995

Multifunctional regulation of the biological effects of TNF-alpha by the soluble type I and type II TNF receptors.

Two soluble receptors of tumour necrosis factor were evaluated for development as potential therapeutic agents for inflammatory disease. The recombinant human soluble Type I and Type II TNF receptors, rsTNF-RI and rsTNF-RII, were expressed at high levels in E. coli, refolded, and chromatographically purified to homogeneity. The potencies of both recombinant soluble receptors were similar to their naturally occurring soluble receptors. In in vitro cytotoxicity and competitive binding assays, both recombinant soluble receptors functioned to inhibit the biological effects of rhTNF-alpha although rsTNF-RI was a 5 to 30 fold more potent inhibitor of rhTNF-alpha than was rsTNF-RII or a truncated form of the soluble receptor, TNF-RII delta. In in vivo experiments in mice, rsTNF-RI was a better inhibitor than rsTNF-RII delta of rhTNF-alpha-stimulated changes in the percentages of circulating lymphocytes and neutrophils, influx of neutrophils into the peritoneal cavity, and serum IL-6 induction. At molar ratios of 0.1:1 and 0.01:1 (rsTNF-R:rhTNF-alpha), using the rsTNF-I or rsTNF-II delta, there was a trend towards enhancement of the induction of IL-6. However, higher ratios of either rsTNF-RI or rsTNF-RII delta significantly inhibited the rhTNF-alpha-stimulated increase in serum IL-6 levels. In a murine model of cytokine-induced shock, either rsTNF-RI or rsTNF-RII delta provided protection against the lethality of shock induced by a synergistic combination of rhTNF-alpha and rhIL-1 beta. Based on the results of these experiments, the rsTNF-RI was chosen as the better candidate for development as an anti-inflammatory agent.

Animals↗
PubMed1995

Energy-dispersive X-ray analysis of the extracellular cadmium sulfide crystallites of Klebsiella aerogenes.

Klebsiella aerogenes forms electron-dense particles on the cell surface in response to the presence of cadmium ions in the growth medium. These particles ranged from 20 to 200 nm in size, and quantitative energy dispersive X-ray analysis established that they comprise cadmium and sulfur in a 1:1 ratio. This observation leads to the conclusion that the particles are cadmium sulfide crystallites. A combination of atomic absorption spectroscopy, inductively coupled plasma mass spectrometry, and acid-labile sulfide analysis revealed that the total intracellular and bound extracellular cadmium:sulfur ratio is also 1:1, which suggests tha the bulk of the cadmium is fixed as extracellular cadmium sulfide. The tolerance of K. aerogenes to cadmium ions and the formation of the cadmium sulfide crystallites were dependent on the buffer composition of the growth medium. The addition of cadmium ions to phosphate-buffered media resulted in cadmium phosphate precipitates that remove the potentially toxic cadmium ions from the growth medium. Electron-dense particles formed on the surfaces of bacteria grown under these conditions were a combination of cadmium sulfide and cadmium phosphates. The specific bacterial growth rate in the exponential phase of batch cultures was not affected by up to 2mM cadmium in Tricine-buffered medium, but formation of cadmium sulfide crystallites was maximal during the stationary phase of batch culture. Cadmium tolerance was much lower (10 to 150 microM) in growth media buffered with Tris, Bistris propane, Bes, Tes, or Hepes. These results illustrate the importance of considering medium composition when comparing levels of bacterial cadmium tolerance.

Cadmium↗
PubMed1995

Inhibition of tumor necrosis factor is protective against neurologic dysfunction after active immunization of Lewis rats with myelin basic protein.

Increasing evidence indicates that the cytokines, tumor necrosis factor (TNF), interleukin-1, and/or interferon-gamma, may play a crucial role in the pathogenesis of multiple sclerosis. Several reports demonstrated that inhibition of TNF is highly protective in experimental allergic encephalomyelitis (EAE) when sensitization is accomplished by the passive transfer of myelin basic protein (MBP) sensitized lymphocytes. However, successful protection has not been reported in EAE that is induced by active immunization with MBP. We examined the effects of a TNF inhibitor, dimeric polyethylene glycol linked form of the type I soluble receptor of TNF, PEG-(rsTNF-RI)2, on actively acquired EAE. Treatment with PEG-(rsTNF-RI)2 at 0.3-3 mg/kg every other day or every third day starting on Day 9 postimmunization with MBP during the effector phase of EAE significantly inhibited clinical signs in a dose-dependent manner. Histological examination of the central nervous system indicated that the administration of PEG-(rsTNF-RI)2 reduced, in part, the cellular infiltrate, particularly in the lumbar and sacral regions of the spinal cord. These studies suggest that TNF is a pivotal mediator of the inflammation resulting from the complete immune response induced by active immunization with MBP.

Animals↗
PubMed1995

In vivo spectroscopic properties of the fluorescent pH indicator biscarboxyethyl carboxyfluorescein.

Transcutaneous detection of fluorescence from an injection of the pH-sensitive probe biscarboxyethyl carboxyfluorescein (BCECF) has been used to monitor plasma pH in conscious animals. The fluorescence signal must be calibrated with reference to a standard curve. This standard, calibration curve has been achieved using in vitro methods. Here it is shown that temperature influences the calibration curve determination in vitro and hence influences the pH determined from transcutaneous measurements. Two calibration curves have been obtained, one at room temperature (approximately 25 degrees C) and the other at 37 degrees C. At pH 7.01 the calibration curves intersect, so that, at more alkaline pH values, use of room temperature calibration data will lead to an overestimate of plasma pH. Below pH 7.01, plasma pH will be underestimated. Transcutaneous fluorescence spectra recorded from a mouse injected with BCECF are shown, indicating that baseline plasma pH was estimated about 0.3 pH units too high using room temperature calibration, and that the extent of acidification when the animal was allowed to breathe an atmosphere containing 15% CO2 was overestimated by 0.7 pH units. Additionally, it is shown that in vitro bovine serum albumin at concentrations comparable with albumin concentrations in vivo shifts the absorption, fluorescence excitation and emission spectra of BCECF. However, fluorescence spectra recorded in vivo show no such shift. The results indicate that in vitro calibration for transcutaneous fluorescence measurements in vivo can be misleading, and that in the case of pH measurement inattention to temperature can lead to spurious results.

Animals↗
PubMed1995

Combined inhibition of interleukin-1 and tumor necrosis factor in rodent endotoxemia: improved survival and organ function.

The interleukin (IL)-1 receptor antagonist (Ra) and a polyethylene glycol-linked dimer of the type I soluble receptor of tumor necrosis factor (TNF), PEG-(rsTNF-RI)2, were used to determine whether maximal protection against lethality and organ dysfunction is achieved by single or dual cytokine inhibition under rigorous conditions of rodent endotoxemia. Inhibition of IL-1 or TNF alone protected maximally against lethality when inhibitors were given simultaneously with lipopolysaccharide (LPS) under minimal lethal conditions. Combined inhibition of IL-1 and TNF was necessary to maximally protect against lethality when treatment was delayed until 7 h after LPS injection under minimal lethal conditions or when treatment was begun immediately after LPS injection under supralethal conditions. Improved survival in IL-1Ra- plus PEG-(rsTNF-RI)2-treated rats was associated with enhanced protection against renal and metabolic dysfunctions. Thus, under very severe conditions of endotoxemia, TNF and IL-1 may act independently to mediate lethality and some organ dysfunctions.

Animals↗
PubMed1995

On the source of the oscillations observed during in vivo zinc phthalocyanine fluorescence pharmacokinetic measurements in mice.

Surface-detected fluorescence spectroscopy can be used to monitor the pharmacokinetics of uptake and clearance of red-absorbing fluorophores such as zinc(II) phthalocyanine (ZnPc) in vivo. When this technique is applied to mice that have been fed on a normal chlorophyll-based diet, and particularly when measurements are performed in the abdominal region, oscillations are sometimes observed superimposed on the pharmacokinetic curve of the ZnPc. An oscillatory signal has also been observed arising from the abdominal region of control mice fed a normal diet but not injected with the ZnPc photosensitizer; this oscillatory component to the signal is reduced when mice are fed a chlorophyll-free diet. The oscillatory signal component has been attributed to fluorescence arising from chlorophyll derivatives (pheophorbide/pheophytin) contained in the rodent food, whose concentration in the measured abdominal region changes substantially with time, presumably due to digestive processes. Thus it is important to be aware of the possibility of such artifactual contributions to in vivo fluorescence pharmacokinetic measurements.

1,2-Dipalmitoylphosphatidylcholine↗