Biomedical subjects

R C Myers

Publications and source records attributed to R C Myers.

At least 19 recordsLinked to original sources

PubMed2003

Gigahertz electron spin manipulation using voltage-controlled g-tensor modulation.

We present a scheme that enables gigahertz-bandwidth three-dimensional control of electron spins in a semiconductor heterostructure with the use of a single voltage signal. Microwave modulation of the Landé g tensor produces frequency-modulated electron spin precession. Driving at the Larmor frequency results in g-tensor modulation resonance, which is functionally equivalent to electron spin resonance but without the use of time-dependent magnetic fields. These results provide proof of the concept that quantum spin information can be locally manipulated with the use of high-speed electrical circuits.

Journal Article↗

PubMed2002

Difficulties associated with the development and licensing of vaccines for protection against bio-warfare and bio-terrorism.

Today there is an increasing need to license vaccines for the protection of individuals against bio-warfare and bio-terrorism. While the need is apparent, the actual road to developing, producing and licensing such vaccines successfully is as yet undefined. Bio-defence vaccine candidates may come from several sources. They may come from vaccines that were previously licensed but are no longer in production, vaccines that are currently in an IND status, vaccines currently licensed in foreign countries, and newer vaccines currently under development. The issues that apply to the development and licensing of these vaccines can be defined by currently accepted standards for manufacture, and the requirement to demonstrate safety and efficacy to a level that gives the scientific and medical community, regulatory agencies, users and the public at large confidence. Requirements for manufacturing and demonstration of safety will be consistent with vaccines being developed for traditional purposes. However, demonstration of efficacy will be more difficult. Because field trials for these vaccines are generally not feasible and the conduct of human challenge studies is generally considered unethical, the demonstration of efficacy will need to be based on existing efficacy data, a thorough understanding of both the disease's pathogenesis and mechanism of protection, the ability to identify surrogate markers for efficacy, and the use of the proposed FDA "animal rule".

Biological Warfare↗

PubMed2001

The acute toxicity and primary irritancy of glutaraldehyde solutions.

Glutaraldehyde (GA, CAS Number 110-30-8), an aliphatic dialdehyde, has a wide range of industrial, scientific, and medical applications. It is available in aqueous solutions, whose concentrations vary up to 50% (w/w) and from which there is a potential during use for skin and eye contact and exposure to the vapor. The acute toxicity and primary irritancy of a wide range of GA concentrations were investigated to determine the differential hazards for such solutions. The acute peroral toxicity in the rat, expressed as ml of solution dosed, was moderate for solutions of 5% and above (LD50 range 0.88-3.25 ml/kg) and generally varied little for solutions up to 50%. Solutions less than 5% GA were of slight toxicity (LD50 range 3.34-12.30 ml/kg for 1 and 2% solutions). When lethality was expressed as absolute amount of GA dosed (mg GA/kg), there was a reciprocal relationship between the concentration of GA solution dosed and LD50. This was confirmed in the mouse, which is more susceptible than the rat to acute peroral toxicity. The acute percutaneous toxicity of GA solutions to rabbits (24 h occlusion) was moderate (LD50 range 1.59-2.71 ml/kg) for 46 and 50% solutions, and slight for 25% GA solutions (8.80-16.00 ml/kg). At 15% and less, 16.0 ml/kg was not lethal. Exposures (4-8 h) of rats to saturated vapor atmospheres of GA generated dynamically or statistically at ambient temperature (17-25 C) produced only transient peripheral sensory irritant effects to the eyes and respiratory tract. In contrast, vapor atmosphere generated dynamically at elevated temperature (60 or 65 C) produce severe effects, including mortality (4-h LC50 range 23.5-44.3 ppm). Histopathology in rats that died included exposure concentration-related acute inflammation and necrosis in the nasal mucosa, larynx, trachea, and bronchi. Standard primary skin irritation tests in the rabbit indicated severe skin irritation and necrosis at 45 and 50% GA; necrosis occurred with 1 and 4 h contact at 50% and at 4 h with 45%. Inflammation was moderate at 25%, slight to moderate with 5 and 10% GA, minor at 2%, and threshold at 1%. Standard primary eye irritation tests showed 45% GA to produce severe conjunctival and corneal injury, which was persistent. At 2% GA corneal injury was mild, and at 5% marked. The lowest concentration producing corneal injury was 1.0%, and the no-effects concentration was 0.5%. The threshold for conjunctival effects was 0.2%, and the no-effects concentration 0.1%. At 1% GA, conjunctival hyperemia and chemosis were moderate to marked, and became more severe with higher GA concentrations. The results suggest potential acute handling hazards with various concentrations of GA solutions and indicate industrial hygiene considerations.

Administration, Cutaneous↗

PubMed2000

Black holes radiate mainly on the brane.

We examine the evaporation of a small black hole on a brane in a world with large extra dimensions. Since the masses of many Kaluza-Klein modes are much smaller than the Hawking temperature of the black hole, it has been claimed that most of the energy is radiated into these modes. We show that this is incorrect. Most of the energy goes into the modes on the brane. This raises the possibility of observing Hawking radiation in future high energy colliders if there are large extra dimensions.

Journal Article↗

PubMed2000

Acute toxicity, primary irritancy, and genetic toxicity studies with 3-(methylthio)propionaldehyde.

Basic acute toxicity, primary irritancy, and genetic toxicity studies were conducted with 3-(methylthio)propionaldehyde (3-MTP). The acute rat peroral LD50 (with 95% confidence limits) for 3-MTP as a 25% (v/v) dilution in corn oil was 1.00 (0.59-1.70) ml/kg (males) and 1.68 (0.95-2.99) ml/kg (females); most deaths occurred 1.5 to 4 h postdosing. By 24-h occluded contact with undiluted 3-MTP, the rabbit acute percutaneous LD50 was 0.71 (0.43-1.15) ml/kg (males) and 0.79 (0.49-1.30) ml/kg (females): times to death ranged from 2 h to 2 d after the start of dosing. Exposure of rats to a statically generated saturated atmosphere killed all 5 males with a 40 min exposure and all 5 females with a 24 min exposure. In contrast, a 4-h exposure of rats to a dynamically generated saturated vapor atmosphere of 3-MTP did not produce any mortalities or signs of toxicity. A 4-hr occluded contact with 0.5 ml undiluted 3-MTP caused moderate to severe erythema and severe edema resolving by 7 to 17 d. Five/6 animals had necrosis apparent on removal of the occlusive dressing and persisting 10 to 17 d. On the rabbit eye, 0.1 ml undiluted 3-MTP produced moderate to severe corneal injury with iritis and moderate conjunctival inflammation which persisted 21 d in 3/6 animals; 0.01 ml caused moderate diffuse corneal injury and moderate conjunctival inflammation with healing by 7 d. 3-MTP did not produce mutagenic activity either in the absence or presence of metabolic activation with a Salmonella typhimurium reverse mutation assay using strains TA98, TA100, TA1535, TA1537 and TA1538. In a mouse lymphoma cell (L5178Y/tk +/-) assay, 3-MTP produced concentration-related increases in mutant colonies, both in the absence and presence of metabolic activation. Increases were mainly in the sigma (chromosomal damaging) colonies. In a mouse bone marrow micronucleus study, with vapor exposures to 37.4, 88.5 and 155.6 ppm for 1 h/d for 2 consecutive d, there were exposure concentration-related increases in micronucleated erythrocytes which were statically significant for male mice.

Administration, Cutaneous↗

PubMed1997

Influence of alkalinization of glutaraldehyde biocidal solutions on acute toxicity, primary irritancy, and skin sensitization.

Aqueous glutaraldehyde (GA) is used at a concentration around 2% for the cold sterilization of endoscopy and dental instruments. Stock GA solution (pH 3.1-4.5) is alkalinized (pH 7.8-8.0) before use to optimize biocidal activity. The possible differential handling hazards between acidic unbuffered GA (UGA) and alkaline buffered GA (BGA) were compared for acute toxicity, primary irritancy and skin sensitizing potential using a 2.2% GA solution. Peroral LD5.0 values (with 95% confidence limits) in rats (combined sexes) were 3.45 (3.13-3.80) g/kg for UGA and 4.16 (3.13-5.52) g/kg for BGA; signs and gross pathology were similar. A 24-h occluded cutaneous application of 16.0 g/kg in the rabbit did not produce mortality; moderate skin irritancy was observed. No systemic effects occurred with UGA and only a few with BGA (unsteady gait, sluggishness, rapid breathing). Local skin irritation from a 4-h occluded contact with 0.5 ml was relatively minor and slightly more marked with BGA than UGA. Rats exposed to a statistically generated saturated vapor atmosphere for 6 h did not show any signs or gross pathology, and only slight weight loss occurred (UGA females). Rabbit eye irritation studies (0.1 ml) showed slightly more marked conjunctival reactions with BGA, but corneal injury was marked and persistent with BGA and only slight and transient with UGA. With 0.01 ml, no corneal injury occurred, but conjunctival reaction was more marked with UGA. A guinea pig maximization study showed UGA to produce a higher sensitizing index (68% at challenge, 32% at rechallenge) than BGA (30% at challenge, 5% at rechallenge). Severity indices at challenge was also higher for UGA [0.84 (24 h), 0.47 (48 h)] than BGA [0.45 (24 h), 0.18 (48 h)]. Both UGA and BGA have generally similar acute toxicity and skin irritancy; BGA has greater corneal injuring potential, and UGA has a greater skin sensitizing potential.

Animals↗

PubMed1992

The acute toxicity, primary irritancy and skin sensitizing potential of glutaric anhydride.

Glutaric anhydride (GA), an industrial chemical, was found of moderate acute peroral lethal toxicity with LD50 values (95% confidence limits) in the rat of 1.41 (0.80-2.49) g/kg (males) and 0.54 (0.36-0.79) g/kg (females), with death being due in part to gastrointestinal irritancy. Dilution with water given by gavage after peroral dosing had no effect on lethal toxicity. Acute percutaneous LD50 values (rabbit) by 24-h occlusion were 6.25 (5.34-7.33) g/kg in males and 5.66 (3.21-9.95) g/kg in females; local skin effects included erythema, edema, necrosis and ulceration. A 6-h exposure to a statically generated saturated vapor atmosphere (rat) produced no signs of toxicity or irritancy. A 4-h, but not 1-h or 3-min occluded contact with 0.5 g of moistened GA (rabbit) produced erythema, edema and necrosis. Contamination of the eye (rabbit) with 10 mg GA produced conjunctivitis (hyperemia, chemosis and discharge) which persisted 7 to 14 d, mild iritis of 2 to 14 d duration, and mild to severe corneal injury which healed within 14 d. A maximization study in guinea pigs by the method of Magnusson and Kligman showed no potential for skin sensitization with GA. The major acute hazards of GA were by swallowing, eye contact and sustained skin contact.

Administration, Cutaneous↗

PubMed1991

Evaluation of intravenous administration of concentrated immunoglobulin G to colostrum-deprived foals.

Ten foals of various breeds were deprived of colostrum from birth to 36 hours of age, then were allotted to 2 groups. Foals of group 1 (n = 6) were given 20 g (200 ml) of purified equine IgG IV in a 10% solution, and foals of group 2 (n = 4) were given 30 g (300 ml) of the same preparation. Total administration time for each 10 g of IgG in 100 ml was approximately 10 minutes. Serum IgG concentration in foals was assessed prior to, between 24 and 48 hours, and at 7 and 14 days after IgG administration. Between 24 and 48 hours after IgG administration, mean serum IgG concentration in group-1 foals was 425 mg/dl (range, 350 to 480 mg/dl). Mean body weight for this group of foals was 50.3 kg (range, 43.3 to 54.7 kg). For group-2 foals, mean serum IgG concentration was 768 mg/dl (range, 640 to 920 mg/dl) between 24 and 48 hours after administration of IgG. Foals of this group had mean body weight of 43.2 kg (range, 36.5 to 47.5 kg). Serum IgG concentration in group-2 foals at 24 to 48 hours was significantly (P = 0.005) greater than that in group-1 foals. Mean total IgG recovery at 24 to 48 hours, calculated on the basis of 94.5 ml of plasma volume/kg of body weight, was approximately 100%. Values of IgG measured in all foals 1 and 2 weeks after administration of the IgG concentrate were equivalent to values expected after normal decay of passively acquired IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Chemiluminescence in a macrophage cell line modulated by biological response modifiers.

We have studied a murine macrophage cell line, J774, and found these cells capable of a zymosan-triggered chemiluminescent oxidative burst. Such activity was enhanced by preincubation with Corynebacterium parvum (CP), bacillus Calmette-Guerin, and lipopolysaccharide (LPS). Under similar conditions, CP and LPS were shown to enhance J774-mediated tumor cell lysis. We have also demonstrated that murine interferon alpha + beta rendered J774 cells more sensitive to the actions of CP and LPS. These results indicate that J774 cells may be useful for the in vitro evaluation of biological response modifiers as well as the study of oxygen radical production by macrophages.

Adjuvants, Immunologic↗

PubMed1989

Modulation of hematoporphyrin derivative-sensitized phototherapy with corynebacterium parvum in murine transitional cell carcinoma.

The interaction of photodynamic therapy (PDT) with hematoporphyrin derivative (Hpd) and immunotherapy with Corynebacterium parvum (CP) was studied in a murine transitional cell carcinoma (MBT-2) model. C3H/He mice were transplanted subcutaneously in the hind limb with 2.5 X 10(5) tumor cells. One day after transplantation, mice were randomized into groups to receive saline (control), PDT, CP 25 micrograms, CP 250 micrograms, CP 25 micrograms + PDT, and CP 250 micrograms + PDT. PDT was administered by intraperitoneal (IP) injection of Hpd (12.5 micrograms/g body weight), followed twenty-four hours later by photoirradiation. CP was given intralesionally at the same time as IP injection of Hpd (24 hours before photoirradiation). A low dose of CP (25 micrograms) was shown to enhance the effect of PDT while PDT reduced the benefit obtained with high dose of CP (250 micrograms). In a second series of experiments, CP (250 micrograms) treatment after photoirradiation was shown to give significantly greater benefit than CP treatment before photoirradiation. The study thus indicates that the effectiveness of combined immunophototherapy is dependent on the sequence of the combination and its intricate relationship with the dosage of CP. The enhancement of PDT by low dose of CP in this model suggests the usefulness of this combined immunophototherapy in enhancing tumor control and in lessening deleterious side effects.

Animals↗

PubMed1989

The acute toxicity of tris(dimethylamino)silane.

The acute handling hazards of tris(dimethylamino)silane [TDMAS] were investigated. The acute male rat peroral LD50 (with 95% confidence limits) was 0.71 (0.51-0.97) ml/kg, and the acute male rabbit percutaneous LD50 was 0.57 (0.35-0.92) ml/kg. The liquid was severely irritating to the rabbit eye and skin, and the vapor severely irritating to the rat eye. The dynamically generated saturated vapor Lt50 in female rats was 12 (9.7-15) min. The effect of varying the atmospheric concentration of vapor from TDMAS on acute inhalation toxicity was investigated by passing ordinary moist air countercurrent to liquid TDMAS metered into a slightly heated glass tube. Based on nominal concentrations, the 4 hr-LC50 for vapor from TDMAS was 734 (603-893) ppm in female rats by this procedure. Stoichiometrically, this accords with toxicity due to liberation of dimethylamine (DMA) from TDMAS. In a subsequent study designed to assess the influence of relative humidity on vapor toxicity, nitrogen was passed over heated liquid TDMAS and the resultant atmosphere was introduced into the air intake duct of the inhalation exposure chamber. Gas chromatographically measured TDMAS concentrations (+/- SD) were 395 +/- 111, 127 +/- 25, 62 +/- 8 and 23 +/- 21 ppm; the corresponding DMA vapor concentrations were 112 +/- 171, 31 +/- 43, 10 +/- 6 and 26 +/- 44 ppm. The 4-hr LC50 (males and females) was 38 (34-43) ppm TDMAS vapor. Thus, TDMAS is of moderate acute peroral and percutaneous toxicity, a severe primary skin and eye irritant, an aspiration hazard, and of high intrinsic acute inhalation toxicity, but in moist air conditions lethal toxicity may be reduced and in such circumstances DMA may be a significant factor in toxicity.

Administration, Inhalation↗

PubMed1988

The acute toxicity and mutagenic potential of 3-methyl-2-benzothiazolinone hydrazone.

3-Methyl-2-benzothiazolinone hydrazone (MBTH), widely used in analytical laboratories, was investigated for potential handling hazards. Tested as the hydrochloride, it was found to be of moderately high acute peroral toxicity with LD50 values in rabbits of 177 mg/kg (males) and 268 mg/kg (females), and in the rat 308 mg/kg (males) and 149 mg/kg (females). The major signs of toxicity, seen at peroral doses of 125 mg/kg and above, were convulsions. Although of low acute lethal percutaneous toxicity in rats (LD50 greater than 16 g/kg), rabbits were more sensitive with one of five males dying at an applied dose of 16 g/kg, and females having an LD50 of 12.3 g/kg; convulsions were seen in rabbits having applied cutaneous doses of 4 g/kg and above. There was no evidence for cutaneous inflammation after a 4 hour occluded contact with MBTH in rabbits, although following 24 hour occlusive contact in the acute percutaneous toxicity study there was erythema, edema, desquamation and, in a few animals, local necrosis. Ocular studies in rabbits indicated that, depending on the degree of contamination, MBTH produced mild to moderate eye irritation. In keeping with its low vapor pressure, there were no adverse effects from a 6 hour exposure of rats to an atmosphere saturated with any vapor produced from solid MBTH at ambient temperature. MBTH was positive in an Ames bacterial mutagenicity assay, particularly in the absence of metabolic activation. These studies indicate MBTH to be of moderately high acute peroral toxicity, of moderate percutaneous toxicity, a mild primary skin irritant, a mild to moderate eye irritant, and produced mutations in Salmonella. There is a need for skin and eye protection, and avoidance of swallowing, when handling MBTH.

Animals↗

PubMed1988

Acute toxicity and primary irritation of para-tertiary butylphenol.

Para-tertiary butylphenol [(PTBP); the Union Carbide Corporation trademark for this chemical is UCAR Butylphenol 4-T Flake] has applications as a raw material in the manufacture of resins and also as an industrial intermediate. Acute peroral LD50 values (95% confidence limits) of 5.4 (3.6-7.9) g/kg and 3.6 (3.0-4.4) g/kg were obtained for male and female albino rats, respectively. Occluded cutaneous applications of moistened PTBP at 16 g/kg for 24 hr produced no mortalities in male or female rabbits, but signs of local toxicity and irritation were apparent at the site of application. A 6 hr exposure to a substantially saturated vapor under static conditions produced no mortality, while a 4 hr exposure to a dynamically generated respirable dust aerosol at a concentration of 5.6 mg/L produced 20% mortality. Occluded dermal contact (4 hr) with 0.5 g moistened PTBP produced a range of effects from no reaction to necrosis. PTBP placed in the conjunctival sac of rabbits produced severe ocular injury which generally persisted for 21 days after exposure. The major hazard associated with acute exposure to PTBP appears to be the irritation produced by dermal or ocular contact.

Administration, Cutaneous↗

PubMed1988

The acute toxicity of methoxydihydropyran.

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Administration, Cutaneous↗

PubMed1988

The acute toxicity and primary irritancy of 1-propoxy-2-propanol.

1-Propoxy-2-propanol, a widely used industrial chemical, was found to have acute peroral LD50 values in the rat of 4.92 ml/kg (males) and 2.83 ml/kg (females), with the signs of systemic toxicity being principally related to narcosis. Acute percutaneous LD50 values in the rabbit (24-hr occluded) were 4.29 ml/kg (males) and 4.92 ml/kg (females); signs of systemic toxicity were related to narcosis, and local effects were severe inflammation and corrosion. There were signs of sensory irritation of the eye during a 6-hr exposure to a dynamically generated saturated vapor atmosphere, but no signs of toxicity during exposure or in a 14-hr day postexposure observation period. A 4-hr occluded cutaneous application with 0.5 ml PP in rabbits produced mild to moderate erythema and edema of about 3 days duration, but no signs of corrosion. Contamination of the eye (0.005 to 0.1 ml PP) produced moderate to severe conjunctivitis (hyperaemia and chemosis), with mild iritis and diffuse mild keratitis; spontaneously healing occurred within 3 days (0.005 ml) to 7 days (0.1 ml). The major acute hazards with PP are by swallowing, splash contamination of the eye, and sustained skin contact.

Administration, Inhalation↗

PubMed1987

The comparative acute toxicity and primary irritancy of the monohexyl ethers of ethylene and diethylene glycol.

Ethylene glycol monohexyl ether (EGHE) and diethylene glycol monohexyl ether (DGHE) are glycol ethers used as industrial solvents and coating materials, and whose acute handling hazards were investigated. Acute peroral LD50 values in the rat were for EGHE 1.67 ml/kg (males) and 0.83 ml/kg (females), and for DGHE 4.92 ml/kg (males) and 3.73 ml/kg (females). Acute percutaneous LD50 values in the rabbit were for EGHE 0.81 ml/kg (males) and 0.93 ml/kg (females), and for DGHE 2.14 ml/kg (males) and 2.37 ml/kg (females). There were neither deaths nor signs of toxicity or irritancy during or following a 6-hr exposure of rats to a statically generated substantially saturated vapor atmosphere from either EGHE or DGHE at ambient temperature. Occluded dermal application with 0.5 ml test material for 4-hr in rabbits produced moderate inflammation of several days duration, and half of the animals developed necrosis; with DGHE there was minor erythema and edema of about 24-hr duration. In the more demanding conditions of the acute percutaneous toxicity study (24-hr occlusions with up to 4.0 ml/kg) both EGHE and DGHE produced persistent erythema, edema, necrosis, and ecchymoses. Rabbit eye irritation studies showed severe effects (conjunctivitis and corneal injury) with both EGHE and DGHE. The major acute handling hazards with both EGHE and DGHE are by swallowing, sustained skin contact, and splash contamination of the eye.

Administration, Cutaneous↗

PubMed1986

Selenium-induced enhancement of hematoporphyrin derivative phototoxicity in murine bladder tumor cells.

The phototoxicity of hematoporphyrin derivative (Hpd) to murine bladder tumor (MBT-2) cells was studied in vitro. It was observed that selenium in the form of sodium selenite enhanced Hpd-sensitized photodamage in MBT-2 cells under conditions where selenite alone was non-toxic. Sodium selenite enhanced the fluorescence emission of Hpd and augmented the Hpd-sensitized photooxidation of tryptophan. The data suggest that sodium selenite is able to disaggregate Hpd, thereby enhancing Hpd-sensitized phototoxicity.

Animals↗

PubMed1986

Studies on the acute toxicity primary irritancy and genotoxic potential of 1,3,5-triacryloylhexahydro-s-triazine (TAHT).

TAHT (1,3,5-triacryloylhexahydro-s-triazine), a reactive chemical coupling agent, was highly toxic following a single peroral dose of an aqueous suspension (10% w/v) to Wistar rats, or following application of TAHT in dichloromethane (DCM) solution (10% w/v) to covered skin of New Zealand rabbits. It was moderately toxic when applied dermally as an aqueous paste. Ocular contact with 25 mg of TAHT in a 5% aqueous suspension, or of 0.5 mg of TAHT in a 10% (w/v) solution in DCM, produced severe corneal damage, iritis and blepharo-conjunctivitis. A 30-min exposure of uncovered rabbit skin to 1 mg of TAHT in a 10% (w/v) aqueous suspension produced only slight skin irritation. However, 24-h exposures to TAHT on covered skin produced erythema, edema, ecchymoses, scabs, and death depending upon dosage and vehicle. In vitro genotoxicity studies revealed no positive effects upon gene mutations (HGPRT locus) or on sister chromatid exchanges (SCEs) of CHO cells exposed to TAHT with and without a rat-liver S9 metabolic activation system. TAHT did not increase the levels of [3H]thymidine incorporation in a test for unscheduled DNA synthesis with primary rat hepatocytes. In contrast, substantial increases in the number of chromosome breaks and rearrangements were observed in chromosome preparations used for the SCE analyses. The clastogenic activity of TAHT was confirmed in an in vitro chromosome aberration test with CHO cells. Treatment-related increases in chromosome breakage were observed at two independent sampling times and positive effects did not depend upon the presence or absence of a metabolic activation system. Clastogenic activity of TAHT was also demonstrated in vivo in a micronucleus test using mouse peripheral polychromatic erythrocytes. Significant, treatment-related increases in micronucleated polychromatic erythrocytes were obtained at two of three sampling times. The high degree of mammalian toxicity, severe eye irritancy and the in vitro and in vivo clastogenicity indicate that TAHT should be handled as a hazardous material using suitable caution and protective equipment.

Animals↗