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Biomedical subjects

D Mattson

Publications and source records attributed to D Mattson.

18 recordsLinked to original sources
PubMed2004

Thermal stress and the disruption of redox-sensitive signalling and transcription factor activation: possible role in radiosensitization.

In spite of ongoing research efforts, the specific mechanism(s) of heat-induced alterations in the cellular response to ionizing radiation (IR) remain ambiguous, in part because they likely involve multiple mechanisms and potential targets. One such group of potential targets includes a class of cytoplasmic signalling and/or nuclear transcription factors known as immediate early response genes, which have been suggested to perform cytotoxic as well as cytoprotective roles during cancer therapy. One established mechanism regulating the activity of these early response elements involves changes in cellular oxidation/reduction (redox) status. After establishing common alterations in early response genes by oxidative stress and heat exposure, one could infer that heat shock may have similarities to other forms of environmental antagonists that induce oxidative stress. In this review, recent evidence supporting a mechanistic link between heat shock and oxidative stress will be summarized. In addition, the hypothesis that one mechanism whereby heat shock alters cellular responses to anticancer agents (including hyperthermic radiosensitization) is through heat-induced disruption of redox-sensitive signalling factors will be discussed.

Animals↗
PubMed2004

Heat shock and the activation of AP-1 and inhibition of NF-kappa B DNA-binding activity: possible role of intracellular redox status.

The early response genes comprising the AP-1 and NF-kappa B transcription factors are induced by environmental stress and thought to modulate responses to injury processes through the induction of target genes. Exposure to heat and ionizing radiation (IR) has been shown to affect signalling machinery involved in AP-1 and NF-kappa B activation. Furthermore, regulation of the signalling pathways leading to the activation of these transcription factors has been linked to changes in intracellular oxidation/reduction (redox) reactions. The hypothesis is proposed that exposure to thermal stress and/or IR might alter metabolic processes impacting upon cellular redox state and thereby modify the activity of redox-sensitive transcription factors such as AP-1 and NF-kappa B. Gel electromobility shift assays (EMSA) demonstrated that heat shock-induced AP-1 DNA-binding activity but inhibited IR-induced activation of NF-kappa B. A time course showed that activation of the AP-1 complex occurs between 4 and 5 h following thermal stress, and inhibition of IR-induced NF-kappa B activation also occurs during this time interval. Using a redox-sensitive fluorescent probe [5-(and -6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate], a shift to 40% less intracellular dye oxidation was observed in HeLa cells 0-4 h post-heat shock (45 degrees C, 15 min) relative to cells held at 37 degrees C. This was followed by a shift to greater dye oxidation between 4 and 12 h after treatment (about 1.8-fold) that returned to control levels by 24 h post-heating. These results show changes in DNA-binding activity closely paralleled apparent heat-induced changes in the intracellular redox state. Taken together, these results provide correlative evidence for disruption of redox-sensitive IR-induced signalling pathways by heat shock and support the hypothesis that this mechanism might play a role in heat-induced alterations in radiation response.

DNA↗
PubMed2003

Polyamines as olfactory stimuli in the goldfish Carassius auratus.

Electrophysiological responses of goldfish olfactory receptor neurons (ORNs) and goldfish behavioral responses to polyamines were investigated in vivo. Electro-olfactogram (EOG) recordings indicated that polyamines (putrescine, cadaverine and spermine) are potent olfactory stimuli for goldfish with estimated electrophysiological thresholds of 10(-8)-10(-7) mol l(-1), similar to that for L-arginine, the most stimulatory amino acid. Although thresholds were similar, the magnitude of the EOG responses to intermediate (10(-5)-10(-4) mol l(-1)) and high (10(-3) mol l(-1)) concentrations of polyamines dwarfed the responses to amino acids and related single amine containing compounds (amylamine and butylamine). The EOG responses to 0.1 mmol l(-1) putrescine, cadaverine and spermine were, respectively, 4.2x, 4.3x and 10.3x the response of the standard, 0.1 mmol l(-1) L-arginine. Electrophysiological cross-adaptation experiments indicated that polyamine receptor sites are independent from those to L-amino acids (alanine, arginine, glutamate, lysine, methionine and ornithine), bile salts (sodium taurocholate and taurolithocholate), the single amine containing compounds (amylamine and butylamine) and ATP. Further, the cross-adaptation experiments revealed the existence of independent receptor sites for the different polyamines tested. Pharmacological experiments suggested that polyamine odorant transduction does not primarily involve the cyclic AMP and IP(3) second messenger pathways. Behavioral assays indicated that polyamines are attractants that elicit feeding behavior similar to that elicited by L-amino acids.

Amines↗
PubMed2001

Corynebacterium jeikeium bacteremia in bone marrow transplant patients with Hickman catheters.

Prior studies suggest that Corynebacterium jeikeium bacteremia in immunocompromised patients results in frequent morbidity that may be decreased by prompt removal of the indwelling catheter. To summarize recent experience, charts of 53 bone marrow transplant recipients with Hickman catheters and C. jeikeium bacteremia were reviewed. Forty-one patients were treated with vancomycin without catheter removal and 10 patients underwent catheter removal with subsequent vancomycin therapy. No patient in either group died with C. jeikeium bacteremia as the proximate cause. Salvage of the intravascular catheter was successful in 38 of 41 (93%) attempts. Three patients (7%) in the catheter-salvage group and one patient (10%) in the catheter-removal group experienced recurrent bacteremia. In both catheter-salvage and catheter-removal groups, median time to negative blood culture was 2 days. Thus, time to clearance of bacteremia and patient clinical outcome did not differ between treatment groups. In many patients with Hickman catheters, C. jeikeium bacteremia may be treated successfully with vancomycin and without removal of the catheter.

Adolescent↗
PubMed2001

Characterization of the Oregon isolate of Neospora hughesi from a horse.

Neospora hughesi was isolated in cell cultures inoculated with homogenate of spinal cord from a horse in Oregon. Tachyzoites of this Oregon isolate of N. hughesi were maintained continuously by cell culture passage and tachyzoites were infective to immunosuppressed mice. Gamma interferon gene knockout (KO) mice injected with tachyzoites developed fatal myocarditis and numerous tachyzoites were seen in lesions. Gerbils (Meriones unguiculatus) inoculated with tachyzoites developed antibodies (> or = 1:500) as indicated by the Neospora caninum agglutination test but did not develop clinical signs, and Neospora organisms were not demonstrable in their tissues. Tissue cysts were not found in gerbils, nude mice, KO mice, immunosuppressed outbred Swiss Webster mice, or BALB/c mice injected with the Oregon isolate of N. hughesi. Ultrastructurally, tachyzoites of the Oregon isolate from the myocardium of infected KO mice and from cell culture were similar to N. caninum tachyzoites. Western blot analysis using NcSAG1 and NcSRS2 polyclonal and monoclonal antibodies and characterization of the internal transcribed spacer 1 sequences from the equine isolates and different isolates of N. caninum from dogs and cattle indicated that the Oregon isolate of N. hughesi is distinct from N. caninum isolates from cattle and dogs.

Animals↗
PubMed1999

Elevated salivary cortisol in the evening in healthy elderly men and women: correlation with bone mineral density.

BACKGROUND: Aging is associated with a loss of bone mineral density (BMD) in men and women. Loss of BMD can also be caused by hypercortisolemia in men or women at any age. This study measured salivary cortisol at 2300 h and 0700 h as indices of cortisol secretory activity in 228 elderly, community-dwelling subjects. Salivary cortisol results were correlated with BMD. We hypothesized that salivary cortisol is elevated at 2300 h in elderly people, and that salivary cortisol will correlate negatively with BMD. METHODS: Saliva was sampled at 2300 h (nadir in circadian rhythm) and 0700 h (peak in circadian rhythm) in 130 men (70.7 +/- 0.4 years old) and 98 women (70.0 +/- 0.4 years old); approximately half of the women were receiving hormone replacement therapy (HRT). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Salivary cortisol at 2300 h was significantly elevated in men (2.3 +/- 0.1 nmol/L) and women (2.1 +/- 0.1 nmol/L) as compared to 73 younger controls (1.2 +/- 0.1 nmol/L; 37 +/- 1 year old). Salivary cortisol at 0700 h was not different between older subjects and younger controls. There was a significant negative correlation of lumbar (L2-4) BMD and 2300 h salivary cortisol in older women (r = -0.20, p = .05; n = 98); this correlation was significant only in women not on HRT. There was a highly significant negative correlation of lumbar (L2-4) BMD and 0700 h salivary cortisol in older men (r = -0.31, p = .0003). CONCLUSIONS: Salivary cortisol is a simple, nonstressful method for assessing activity of the hypothalamic-pituitary-adrenal (HPA) axis in the elderly population. A major finding was an elevation in the late night nadir in cortisol secretion. We also suggest that elevated cortisol secretion in elderly people may contribute to the age-related loss in bone mineral density and that this effect is prevented by HRT.

Aged↗
PubMed1998

Axial movements are relatively preserved with respect to limb movements in aphasic patients.

Apraxia is commonly manifested during the acute stage following left hemisphere cerebrovascular accident and typically co-occurs with aphasia. We examined 30 acute stroke patients with aphasia and apraxia in order to determine if such patients show evidence of preservation of selective subclasses of movements. Although Geschwind noted the preservation of axial movements to command in aphasic apraxic patients, his views were subsequently refuted. However, we found that aphasic apraxic patients of varying degrees of severity, including patients with global aphasia, showed relative preservation of axial movements to command and imitation. Theoretical interpretations and implications for acute neurologic rehabilitation are discussed.

Analysis of Variance↗
PubMed1998

Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation.

Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition.

Adolescent↗
PubMed1998

Nerve conduction block by nitric oxide that is mediated by the axonal environment.

Conduction in rat peripheral nerve has been monitored following the stimulated release of nitric oxide (NO) from diethylamine-NONOate (DEA-NONOate). Branches of the sciatic nerve were dissected, but left otherwise intact, and propagating signals recorded externally. At levels consistent with inflammation, NO exposure resulted in a complete loss of the compound action potential. Conduction was fully restored on removal of the drug. Most notably, this loss of excitability was dependent on the axonal environment. Removal of the connective tissue sheaths surrounding the nerve bundle, a process that normally enhances drug action, prevented block of signal propagation by nitric oxide. The epineurium seemed not to be required, and the decreased susceptibility to NO appeared to be correlated with a gradual loss of a component of the endoneurium that surrounds individual fibers. Tested on the rat vagus nerve, NO eliminated action potentials in both myelinated and unmyelinated fibers. One chemical mechanism that is consistent with the reversibility of block and the observed lack of effect of 8-Br-cGMP on conduction is the formation of a nitrosothiol through reaction of NO with a sulfhydryl group. In contrast to DEA-NONOate, S-nitrosocysteine, which can both transfer nitrosonium cation (NO+) to another thiol and also release nitric oxide, was effective on both intact and desheathed preparations. It has previously been demonstrated that chemical modification of invertebrate axons by sulfhydryl-reactive compounds induces a slow inactivation of Na+ channels. Nitric oxide block of axonal conduction may contribute to clinical deficits in inflammatory diseases of the nervous system.

Action Potentials↗
PubMed1996

Hepatic mucormycosis in a bone marrow transplant recipient who ingested naturopathic medicine.

This case report describes a bone marrow transplant recipient in whom hepatic zygomycosis developed after ingestion of multiple naturopathic medicines. Mucor was isolated from the patient's liver aspirate and from one of the naturopathic medicines. Arbitrary-primed polymerase chain reaction (PCR) analyses were performed on the Mucor isolates from the patient's liver aspirate and from his naturopathic medicine to see if they were genotypically related. Mucor indicus was the species identified in both the patient's liver aspirate and the naturopathic medicine. Arbitrary-primed PCR analysis revealed that these isolates were genotypically identical. We conclude that this bone marrow transplant recipient acquired hepatic mucormycosis from ingestion of a naturopathic medicine containing Mucor.

Adult↗
PubMed1996

Phase I study of intravenous ribavirin treatment of respiratory syncytial virus pneumonia after marrow transplantation.

Respiratory syncytial virus (RSV) pneumonia in marrow transplant recipients is associated with significant mortality. Ribavirin is a nucleoside analog with activity against RSV and in its aerosolized formulation is the only drug approved for treatment of RSV pneumonia in the United States. The clinical use of aerosolized ribavirin has been limited by caregivers' concerns about drug exposure and potential teratogenic effects. Since there is lack of proven efficacy and safety of the aerosolized ribavirin in this setting, we performed a phase I study of intravenous ribavirin treatment. Between November 1993 and May 1994, 10 patients with clinically significant RSV pneumonia at the Fred Hutchinson Cancer Research Center were enrolled. Only 2 of the 10 survived (20%; 95% CI, 3-56). Two of the 10 patients developed acute hemolysis that necessitated discontinuation of the medication. In conclusion, treatment of marrow transplant recipients with RSV pneumonia with intravenous ribavirin did not improve mortality compared with historical controls treated with the aerosolized drug.

Adult↗
PubMed1995

Multiple sclerosis. Sexual dysfunction and its response to medications.

OBJECTIVE: To determine the frequency and nature of sexual dysfunction, as well as its response to medications, in a sample of patients with multiple sclerosis (MS). DESIGN: Retrospective and prospective survey of 65 female and 36 male patients with MS. RESULTS: Sixty-three percent of patients reported that they had less sexual activity, and 35% said that they had less interest in lovemaking than before their diagnosis of MS. Fifty-seven patients reported that they had problems with sexual dysfunction. Sexual dysfunction preceded the diagnosis of MS in only 10 of these patients. A higher percentage of men (78%) than women (45%) reported that they experienced sexual dysfunction (P = .002). Men had prominent erectile dysfunction, women had problems with vaginal lubrication, and both sexes had problems with decreased sensation and achieving orgasm. The presence of sexual dysfunction was associated with the presence of urinary problems (P = .02) and with a history of treatment of (P = .04) or a current report of (P = .02) depression. No association could be found between sexual dysfunction and duration of disease, type of disease, disability score, or presence of fatigue. Twenty of 57 patients with sexual dysfunction reported that they had associated marital problems. Forty-three of 60 patients who discussed sexual problems with their spouses and four of six who tried formal counseling found it helpful. Surprisingly, corticosteroid treatments that were started for problems other than sexual dysfunction resulted in improved sexual functioning in many patients. CONCLUSIONS: Sexual dysfunction is common in patients with MS. Determining the frequency and nature of problems allows issues of sexual dysfunction to be addressed as part of comprehensive care of patients with MS and suggests treatments that could improve their quality of life.

Adrenal Cortex Hormones↗
PubMed1994

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension.

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

Animals↗
PubMed1993

In vivo spin trapping of nitric oxide in mice.

We report here an in vivo spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (.NO) production in the blood circulation of conscious mice. The method is based on the trapping of nitric oxide (.NO) by a metal-chelator complex consisting of N-methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable and water-soluble [(MGD)2-Fe(2+)-NO] complex, which gives rise to a characteristic three-line EPR spectrum of a mononitrosyl-Fe2+ complex (aN = 12.5 G and g(iso) = 2.04) at ambient temperatures. After simultaneous intravenous injection of sodium nitroprusside (an .NO donor) and the [(MGD)2-Fe2+] complex into the lateral vein of the mouse tail, the appearance of the three-line spectrum in the blood circulation of the mouse tail was monitored continuously by using an S-band EPR spectrometer, operating at 3.5 GHz. This represents the first spin trapping of .NO in living animals.

Animals↗
PubMed1990

Immunological studies in tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) and other chronic-progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I (HTLV-I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA-DR and interleukin-2-receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus-specific cytotoxic T-cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T-cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV-I-like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus.

Adolescent↗
PubMed1976

Isolation of a subgroup two adenovirus from calf with weak calf syndrome.

A viral agent, designated Id-1, was isolated from the buffy coat of a calf suffering from weak calf syndrome. The virus replicated on bovine salivary gland cells and caused cytopathic effect within four days after infection-Cytopathic effect was characterized by rounding and clumping of cells. Stained preparations of infected monolayers revealed multiple intranuclear inclusions. The agent was found to be resistant to chloroform, ether, trypsin, sodium desoxycholate, oxytetracycline and a pH range of three to nine. The virus was sensitive to 5-iodo-2'-deoxyuridine and to a temperature of 70 degrees C. Cross neutralization tests with Id-1 antiserum and bovine adenovirus type 7 (strain Fujuroi) antiserum resulted in complete neutralilation of both viruses with four or less antibody units of homologous or heterologous antiserum.

Adenoviridae↗