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Biomedical subjects

R H Hill

Publications and source records attributed to R H Hill.

At least 19 recordsLinked to original sources
PubMed1991

Environmental pathology. Mast cell and eosinophil infiltration in intestinal mucosa of Lewis rats treated with L-tryptophan implicated in human eosinophilia myalgia syndrome.

A recently developed animal model for the L-tryptophan-associated eosinophilia myalgia syndrome was used to examine the small intestine and colon, because there is clinical involvement at these sites in patients. Increased perivascular inflammatory infiltrates rich in degranulating mast cells, eosinophils, and monocytes were seen in the lamina propria of experimental animals when compared with controls. L-Tryptophan-associated disease also shares many clinical features with idiopathic scleroderma/eosinophilic fasciitis, in which there is gastrointestinal involvement as well. These features are similar to those found in the recently described animal model. The apparent morphologic and clinical similarities between these entities suggest that the animal model is suitable for further studying the pathogenesis of the gastrointestinal involvement in all these diseases.

Animals↗
PubMed1990

Gas chromatographic and spectral properties of pentafluorobenzyl derivatives of 2,4-dichlorophenoxyacetic acid and phenolic pesticides and metabolites.

Eleven phenols and 2,4-dichlorophenoxyacetic acid, compounds that may be found in body fluids of humans exposed to pesticides, are derivatized with pentafluorobenzyl bromide and characterized by gas chromatography with electron capture detection. These derivatives are further characterized by positive and negative chemical ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and gas chromatography-Fourier transform infrared spectroscopy. Negative chemical ionization mass spectra of all derivatives have an anionic base peak derived from the parent analyte. In the positive mode the nonchlorinated derivatives have base peaks indicative of the analyte, while chlorinated derivatives are cleaved to give the pentafluorobenzyl cation as base peak. The possibility is explored that ortho-substituted phenols might be formed as byproducts in these derivatizations.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1990

L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat.

Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L-kynurenine was higher in both L-TRP-treated groups compared to the vehicle-treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS.

Animals↗
PubMed1989

Activation of N-methyl-D-aspartate (NMDA) receptors augments repolarizing responses in lamprey spinal neurons.

Current- and voltage-clamp techniques were used to analyze the mechanisms underlying the repolarization during N-methyl-D-aspartate (NMDA)-induced, tetrodotoxin-resistant pacemaker-like oscillations in lamprey spinal neurons. Long-lasting depolarizing current pulses (15-40 mV, 50-400 ms, tetrodotoxin and tetraethylammonium present) were followed by hyperpolarizing afterpotentials even when NMDA receptors were blocked, but they were markedly enhanced by application of N-methyl-D,L-aspartate (NM(DL)A). The afterpotentials were depressed by replacing Ca2+ with Ba2+. During voltage-clamp NM(DL)A enhanced a Ba2+-sensitive outward tail current following voltage steps of 15-40 mV. The outward current remained after injection of Cl-, as did the NMDA-induced membrane potential oscillations observed under current-clamp. These results suggest that the repolarization during NMDA-induced oscillations is due to Ca2+ entry both via NMDA-gated channels and conventional voltage-gated Ca2+ channels, leading to an activation of Ca2+-dependent K+ channels. The afterhyperpolarization following single action potentials, which is also due to Ca2+-dependent K+ channels, was not significantly altered by NMDA receptor activation, suggesting a different location of the Ca2+ entry during the two conditions in relation to the location of the activated Ca2+-dependent K+ channels.

Animals↗
PubMed1989

Chromatographic and spectroscopic properties of hemiacetals of aflatoxin and sterigmatocystin metabolites.

Improved fluorescence detection of aflatoxin B1 by chromatographic analysis is accomplished by conversion to the corresponding hemiacetal, aflatoxin B2a. Because the metabolites aflatoxin M1, aflatoxin P1, aflatoxin Q1, sterigmatocystin, and O-methylsterigmatocystin have the same molecular conversion site, we investigated the chromatographic and spectroscopic properties of hemiacetals of these compounds to assist in confirming aflatoxins and sterigmatocystins in human urine. Nuclear magnetic resonance and infrared absorbance were used to confirm the hemiacetal structure for aflatoxin B1 and sterigmatocystin. The ultraviolet absorbance, fluorescence, and chromatographic properties of the metabolites were investigated. Using these data, we optimized the detection and solvent conditions for high-performance liquid chromatography. We determined that, of the conditions studied, maximum sensitivity and resolution for the native aflatoxins were achieved with a mobile phase of methanol, tetrahydrofuran, and water, a C8 column in series with a C18 column, and fluorescence detection with 365 nm excitation and 430 nm emission wavelengths for aflatoxins B1 and M1 and with 500 nm emission wavelength for aflatoxins P1 and Q1. For the analysis of the hemiacetals, a mobile phase of methanol, acetonitrile, and water provided better chromatography and fluorescence detection. Sterigmatocystin and O-methylsterigmatocystin were readily converted to the hemiacetal forms, which, like the aflatoxins, were more polar and, therefore, earlier eluting by reversed-phase HPLC (methanol, acetonitrile, and water, 236 nm absorbance). These data are important to maximize the sensitivity and confidence for detecting the mycotoxin metabolites in biological specimens.

Acetals↗
PubMed1989

Effects of 5-hydroxytryptamine on the afterhyperpolarization, spike frequency regulation, and oscillatory membrane properties in lamprey spinal cord neurons.

1. Local application of 5-hydroxytryptamine (5-HT) in the area in which a dense 5-HT plexus is located in the lamprey spinal cord leads to a marked depression of the late phase of the afterhyperpolarization (AHP) following the action potential. This effect was observed in motoneurons, premotor interneurons, and giant interneurons, whereas no effect was observed in the sensory dorsal cells and edge cells. 2. The late 5-HT sensitive phase of the AHP was increased in amplitude when calcium entry was enhanced during the prolongation of action potentials caused by tetraethylammonium (TEA). Conversely, a blockade of Ca2+ entry by manganese reduced the AHP amplitude, suggesting that a calcium-dependent current, most likely carried by potassium, underlies the late phase of the AHP in these cells, as is the case in many other types of neurons. 3. The late phase of the AHP could be depressed by 5-HT although no effects were exerted on either the resting input resistance or on the shape of the action potential in 54% of the cells. The membrane conductance increase associated with the late phase of the AHP was markedly attenuated by 5-HT application. 4. In voltage-clamp experiments, Na+ currents and most K+ currents were blocked by tetrodotoxin (TTX) and TEA, respectively. Under these conditions, voltage steps elicited a slow outward current, most likely representing a Ca2+-activated K+ current, which was depressed by 5-HT application. 5. 5-HT does not appear to reduce AHP amplitude by blocking the calcium entry occurring during the action potential. No evidence was obtained for an involvement of second messengers such as adenosine-3':5'-cyclic monophosphate (cAMP), guanosine-3':5'-cyclic monophosphate (cGMP), diacyglycerol, or arachidonic acid. The effect of 5-HT on the late AHP may be due to a direct action on the calcium-dependent potassium channels or on the intracellular handling of Ca2+ ions. 6. The amplitude reduction of the AHP has a profound influence on the spike frequency regulation of any given cell; the frequency of spikes evoked by a given excitatory stimulus is therefore markedly increased by application of 5-HT. 5-HT thus increases the "gain" of the input-output relation of interneurons and motoneurons responsible for generating the locomotor rhythm. In addition, 5-HT causes a prolongation of the depolarized plateau of the N-methyl-D-aspartate (NMDA) receptor-induced membrane potential oscillations, as expected from the 5-HT-induced effects on the Ca2+-activated K+ channels that contribute to the repolarization.

Action Potentials↗
PubMed1989

Laser-induced fluorescence of ectopic endometrium in rabbits.

Endometriosis appears under a wide array of morphologies, and early microscopic disease escapes visual inspection. To improve endoscopic diagnosis, we studied the optical properties of ectopic endometrial tissue, in particular laser-induced fluorescence. Photosensitive drugs were used to obtain a selective signal. Five groups of four rabbits underwent surgical induction of endometriosis and were treated with estrogens for 5 weeks to stimulate growth of the implants. Intramuscular injections of vehicle, tetracycline hydrochloride, 6-demethyl-6-deoxytetracycline hydrochloride, tamoxifen citrate, and clomiphene citrate were given 24 hours before exposure of the tissues to argon-ion laser (351.1 nm + 363.8 nm; power density approximately 1.5 mW/cm2). Fluorescence was documented on photographic film. In controls, peritoneum and ovaries showed a dim, white-yellow fluorescence, whereas other tissues exhibited blue tones. Animals treated with tetracycline hydrochloride or tamoxifen citrate showed yellow fluorescence of active endometrial implants and the uterotomy site. Two implants, histologically without viable glandular tissue, did not fluoresce. Treatment with 6-demethyl-6-deoxytetracycline hydrochloride yielded signals of lower intensity. Clomiphene citrate caused fluorescence of the uterotomy site only. This experiment demonstrates that, of the compounds used, tamoxifen is the best selective photoenhancer for endometriotic implants and clomiphene is best for the uterotomy site. This study establishes the potential of these drugs for photoradiation diagnosis and possible treatment of diseases involving ectopic endometrium.

Animals↗
PubMed1988

Chemical correlates of pathogenicity of oils related to the toxic oil syndrome epidemic in Spain.

The identity of the etiologic agent that caused the 1981 epidemic of toxic oil syndrome in Spain has not been established, and toxicologic study of oil specimens from the outbreak has been hampered by uncertainty about which oils were actually capable of causing illness. To identify chemical characteristics associated with pathogenicity, the authors compared specimens collected during the Spanish government's oil recall program in June and July 1981 from affected and unaffected households in the two contiguous towns of Alcorcón and Leganés (Madrid Province). Oils were blind-coded for laboratory analysis, and personnel with no knowledge of the laboratory results determined whether illness was present in a family. Contamination with free aniline and oleyl, linoleyl, and palmityl anilides was strikingly more frequent and extensive in oils collected from the case (affected) families. There was a clear-cut dose-response effect, with increasing concentrations of aniline and anilides associated with increasing risk of illness. Differences in fatty acid and sterol compositions among oils indicated more rapeseed oil admixture in the case group, but these indicators of rapeseed oil admixture did not contribute significantly to risk after the degree of aniline/anilide contamination had been taken into account. The authors conclude that the presence of relatively high levels of aniline and fatty acid anilides in oil specimens collected during the epidemic in the two towns studied indicates a high probability of the current or prior presence of the etiologic agent of toxic oil syndrome. Although these data do not necessarily indicate that any of the compounds measured actually caused the illness, further toxicologic work should concentrate on oils with substantial concentrations of the marker compounds.

Anilides↗
PubMed1987

Voltage clamp analysis of lamprey neurons--role of N-methyl-D-aspartate receptors in fictive locomotion.

Spinal neurons in the lamprey have been subjected to a voltage clamp analysis of the excitatory currents generated during fictive locomotion with particular reference to the phasic activation of voltage dependent N-methyl-D-aspartate (NMDA) receptors. Voltage-clamped neurons observed during NMDA-induced fictive swimming show excitatory and inhibitory synaptic currents in phase with the ipsilateral and contralateral ventral root discharges, respectively. The excitatory synaptic currents showed a marked voltage dependence suggesting that potential sensitive conductances such as the NMDA ionophore are involved in the synaptic events underlying rhythmic locomotor activity. The effect of NMDA receptor activation during application of tetrodotoxin has also been analyzed during NMDA-induced pacemaker-like oscillations. Such NMDA-induced oscillations are essentially abolished during the voltage clamp. In the presence of NMDA current voltage plots reveal a negative slope conductance in the potential range of the inherent oscillations. The addition of tetraethyl ammonium (TEA) to NMDA solution enhanced a net steady state inward current by more than 10-fold due to a partial block of the outward currents. A kinetic analysis was done with a frequency domain technique using a white noise stimulus to linearly perturb the membrane potential over a wide range of frequencies. The analysis revealed that the induced negative conductance leads to a response which is nearly 180 degrees out of phase with the stimulus at low frequencies. This is an unstable condition which leads to the depolarizing phase of the induced oscillations.

Action Potentials↗
PubMed1987

A laboratory for handling chemical toxicants safely.

The Centers for Disease Control has a special Chemical Toxicant Laboratory (CTL) for handling very hazardous chemicals. It is designed to protect the workers, prevent the release of the chemical toxicant into the surrounding environment, and provide for the scientific integrity of the experiments conducted. A discussion of laboratory ventilation and special containment devices is presented. The design of the CTL, coupled with a realistic set of safety guidelines, provides for the safe conduct of research involving highly toxic chemicals.

Centers for Disease Control and Prevention, U.S.↗
PubMed1987

Fatal parathion poisoning in Sierra Leone.

In May and June 1986, 49 persons in Sierra Leone were acutely poisoned by the organothiophosphate insecticide, parathion. Fourteen people died. Illness occurred in three episodes at two different locations that were 44 km apart. A study of 21 cases and 22 household controls was undertaken to explore which factors were associated with the development of the symptoms. Cases were more likely than controls to have eaten bread in the 4 hours before becoming ill (odds ratio, 12.7; 95% confidence interval, 2.4-83.8). Scrapings of residue from the floor of the truck that had brought the wheat flour from the mill to the general store where the baker purchased it were positive for parathion, suggesting that the flour had been contaminated during transport. Pesticide poisoning is a common problem in the developing world, and public health measures such as restricting the use of parathion may help to prevent fatal poisonings.

Adolescent↗