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Biomedical subjects

R C Straight

Publications and source records attributed to R C Straight.

At least 37 records · Page 2Linked to original sources

Intergradation of two different venom populations of the Mojave rattlesnake (Crotalus scutulatus scutulatus) in Arizona.

Two distinct venom populations of Crotalus scutulatus scutulatus exist in Arizona. The venom of one population (venom A) contains the toxin 'Mojave toxin' and is lacking in hemorrhagic and specific proteolytic activities. The other population (venom B) does not contain Mojave toxin but does produce hemorrhagic and proteolytic activities. The venoms of 15 Crotalus scutulatus scutulatus from regions between the venom A and venom B populations in Arizona were examined for the presence of Mojave toxin by immunochemical assay, lethality by mouse i.p. LD50, proteolytic activity and hemorrhagic activity in mice. Venom protein constituents were analyzed using reverse-phase HPLC. Seven venoms contained both the Mojave toxin of venom A and the proteolytic and hemorrhagic activities of venom B. The i.p. LD50 values of the A + B venoms were 0.4-2.6 mg/kg, compared to 0.2-0.5 mg/kg for venom A individuals and 2.1-5.3 mg/kg for the venom B individuals. HPLC illustrated that the A + B venoms exhibited a combined protein profile of venom A and venom B. These data indicate that an intergrade zone exists between the two venom types which arcs around the western and southern regions of the venom B population. Within these regions, three major venom types can occur in Crotalus s. scutulatus.

Animals↗

Comparative enzymatic study of HPLC-fractionated Crotalus venoms.

1. Ten venoms of the genus Crotalus (Crotalus adamanteus, Crotalus atrox, Crotalus durissus durissus, Crotalus horridus horridus, Crotalus lepidus, Crotalus polystictus, Crotalus molossus molossus, Crotalus pusillus, Crotalus scutulatus scutulatus, venom B, and Crotalus viridis lutosus) were fractionated using HPLC anion and cation exchange chromatography. 2. HPLC venom fractions were tested for hemorrhagic, hemolytic, and proteolytic activities. 3. Crude Virginia opossum (Didelphis virginiana) serum neutralized the hemorrhagic activity of HPLC fractions.

Animals↗

Porphyrin-laser photodynamic induction of focal brain necrosis.

A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scalp with 632 nm argon-dye laser light. Animals were studied at one, two and seven days after irradiation. Blood-brain barrier damage was detected by the intravenous injection of Evans blue, horseradish peroxidase and heterologous immunoglobulins. At one and two days after irradiation, the lesions were characterized by extravasation of immunoglobulin and Evans blue, and by edema, ischemia and infiltration by monocytes. On the seventh day after irradiation, the lesion was smaller than it had been two days after irradiation, and had reactive changes at its edges and coagulative necrosis at its center. Extravasation of Evans blue and immunoglobulin was markedly reduced by the seventh day after irradiation, but uptake of horseradish peroxidase by macrophages located at the periphery of the lesion was evident.

Animals↗

Inactivation and mutagenesis of herpes virus by photodynamic treatment with therapeutic dyes.

Dyes which photosensitize membranes may be clinically useful for photodynamic treatment (PDT) of Herpes simplex virus (HSV) infections. It is important to determine whether the enveloped HSV can be inactivated via membrane damage without affecting the genetic material. Selection of appropriate PDT conditions, including the choice of dye, could minimize viral mutagenesis. We determined the mutagenesis caused by PDT employing three membrane-photosensitizing dyes of potential use in cancer photochemotherapy (Photofrin II, polyhematoporphyrin esters, zinc phthalocyanine tetrasulfonates) and a DNA-photosensitizing dye (proflavine sulfate). The effects were compared to those caused by exposure of HSV to ultraviolet radiation (UV). The procedure consisted of incubating HSV with microgram/ml (microM) concentrations of the dye, irradiating the samples with broad spectrum visible/near-UV radiation (Daylight fluorescent lamps) and assaying the survival of the treated HSV. Zinc phthalocyanine was the most potent dye per absorbed photon for inactivating HSV. In parallel with determination of survival, progeny of the surviving virus were grown for determination of mutagenesis. The progeny virus was harvested and subsequently assayed in the presence and absence of 40 micrograms/ml iododeoxycytidine (ICrd) to determine the frequency of mutation to ICrd resistance. Mutation frequencies were determined for progeny from the 1-4% survival level. For PDT with each membrane-photosensitizing dye, only zinc phthalocyanine increased the mutation frequency over the untreated control. This increase was less than 2-fold. Proflavine increased the mutation frequency 2-3 fold over the untreated control. Ultraviolet produced a 15-20 fold increase over the untreated control.(ABSTRACT TRUNCATED AT 250 WORDS)

Hematoporphyrins↗

Systemic immunosuppression induced by photodynamic therapy (PDT) is adoptively transferred by macrophages.

Some derivatives of hematoporphyrins are strongly retained by tumor tissue as compared to normal tissue, and exposure of these photosensitizers to radiation in the visible spectrum can cause serious biological damage. These properties have been exploited in the development of a new treatment for cancer termed photodynamic therapy (PDT). However, recent studies have also demonstrated that PDT can also induce a state of systemic immunosuppression. The purpose of this study was to determine whether PDT-induced suppression of contact hypersensitivity (CHS) responses was an active phenomenon that could be adoptively transferred by viable splenocytes from PDT-treated mice. Although induction of adoptively transferable suppressor cells in PDT-treated mice required exposure to antigen, the suppressor cells were found to be antigen nonspecific in their function. Furthermore, splenocytes from PDT-treated mice were capable of generating levels of allospecific cytotoxic T lymphocyte (CTL) activity which were comparable to those generated by normal control mice, but the ability of irradiated spleen cells from PDT-treated mice to stimulate a mixed lymphocyte response (MLR) was dramatically impaired. Finally, chromatographic separation of T cells, B cells and macrophages showed that the cell type which mediates adoptively transferable suppression of CHS responsiveness is in the macrophage lineage.

Animals↗

Systemic immunosuppression induced by peritoneal photodynamic therapy.

Although photodynamic therapy is being used increasingly for the diagnosis and treatment of human cancer, its effect on immune responses has received little attention. This aspect was examined in a murine model. Mice given peritoneal photodynamic therapy had markedly decreased contact hypersensitivity responsiveness, not observed with cutaneous photodynamic therapy. The immunosuppression was systemic, because contact hypersensitivity was depressed at distal, unirradiated sites. Photodynamic therapy induced adoptively transferable cells that inhibited contact hypersensitivity responses in naive mice. The immunosuppression was reversible, but persisted for 3 weeks after photodynamic therapy. An acute-phase response characterized by leukocytosis and elevated serum amyloid P levels was observed in mice given photodynamic therapy but not in mice treated with either laser or dye alone. These data suggest a link between the acute-phase response and immunosuppression. Thus, although photodynamic therapy shows promise in cancer treatment, the induction of decreased systemic immunoresponsiveness is an important observation with potentially detrimental consequences.

Acute-Phase Reaction↗

Detection of myotoxin alpha-like proteins in various snake venoms.

Ninety-five venom samples from eight snake genera (Agkistrodon, Bitis, Bothrops, Calloselasma, Crotalus, Sistrurus, Naja and Vipera) including venoms of Crotalus species of different geographical origin were assayed using immunodiffusion or an ELISA for the presence of the small basic protein, myotoxin alpha, known to cause muscle necrosis. Of the eight genera investigated, only Crotalus and Sistrurus venoms contained detectable amounts of myotoxin alpha-like proteins. The venoms of 13 out of 17 rattlesnake species investigated contained proteins immunologically similar to myotoxin alpha, including 12 Crotalus species and one Sistrurus species. The highest amounts were detected in venoms of C. exsul, C. viridis oreganus and C. v. viridis. Qualitative differences in the presence or absence of myotoxin alpha-like proteins were observed in the venoms of C. cerastes, C. horridus, C. lepidus, C. mitchelli, C. scutulatus, C. viridis and S. catenatus specimens of different geographic origin. The toxin was not detected in the venoms obtained from C. adamanteus, C. atrox, C. enyo or C. vegrandis specimens. The toxin appears to be widely distributed among rattlesnake species in the new world, but may vary qualitatively by geographical region in several species and subspecies.

Animals↗

Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear.

Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (Photofrin II, Photofrin Medical, Inc.) (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser (Cooper Laser Sonics, Inc.) with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.

Capillary Permeability↗

Comparison of the optical transmission properties of pulsed and continuous wave light in biological tissue.

The purpose of this study is to compare the optical transmission of the pulsed gold vapor laser (628 nm) to that of the continuous wave argon-pumped dye laser (630 nm) in a homogenous tissue model. Gluteal muscle was taken from a rabbit, and sections of varying thicknesses were made. The tissue samples were positioned at the aperture of an integrating sphere. The laser light was passed through an optical attenuator, coupled to a 600-microns fiber, and then directed onto the surface of the tissue. Transmitted light was collected by the integrating sphere. Light measurements were made with a radiometer. This procedure was repeated for samples of differing thickness using the gold vapor laser as the light source. The identical procedure was performed using the argon-pumped dye laser. No significant difference was found in percent transmission of light using the gold vapor laser as compared to the argon-pumped dye laser.

Animals↗

Olfactory, gas chromatographic and mass-spectral analyses of fecal volatiles traced to ingested licorice and apple.

Volatile components of two foodstuffs with characteristic aromas, apple and licorice, and fecal samples obtained from subjects on high-apple and licorice diets, were analyzed by head-space gas chromatography and gas chromatography-mass spectrometer. The volatile compounds characteristic of the odors of apple and licorice were detected by "sniffing" the GC effluent. The aromatic component of licorice was identified by GC-MS as anethole [1-methoxy-4-(2-propenyl) benzene]. The aromatic component of apple could not be chemically characterized by our GC-MS system even though readily detected by the nose. Head-space, GC-MS analysis of fecal volatiles offers a means of tracing odorous and non-odorous components to ingested foodstuffs with potential applications to clinical and forensic medicine and anthropology.

Allylbenzene Derivatives↗

Venom properties of the rattlesnakes (Crotalus) inhabiting the Baja California region of Mexico.

Seven species of rattlesnakes (genus Crotalus) from Baja, Mexico, were investigated for venom yield, protein content, lethal toxicity, 'Mojave toxin' content and hemorrhagic, esterase (BAEE), phosphodiesterase and protease activities. Venom yield was lowest in C. catalinensis and C. enyo enyo and highest in C. ruber ruber. All venoms exhibited esterase and phosphodiesterase activities, except that three (of 14) specimens of C. e. enyo lacked esterase activity. Protease activity was extremely low or absent in adult C. e. enyo, adult C. mitchellii mitchellii, adult C. viridis caliginis and juvenile C. r. ruber venoms. The venom of C. m. mitchellii was the only venom lacking hemorrhagic activity. This venom also had the highest lethal toxicity (i.p. LD50 0.13 - 0.24 mg/kg) in mice, and was the only venom that exhibited a toxin antigenically related to 'Mojave toxin'.

Animals↗

Geographical variation in Crotalus scutulatus scutulatus (Mojave rattlesnake) venom properties.

Individual venom samples were analyzed from 12 specimens of Crotalus scutulatus scutulatus, from north of Tucson to the extreme southeastern region of Arizona. Six of the specimens, from north of Tucson, produced venom lethal toxicity (i.p. LD50) values in mice of 2.0-6.0 mg/kg. These coincided with the values previously reported for C. s. scutulatus in the Phoenix, Arizona, region and designated as type B venom (Glenn and Straight, 1978). In contrast, the venom LD50 of six individuals from extreme southeastern Arizona, including one individual near Tucson, ranged from 0.22-0.46 mg/kg. This corresponds to the values for C. s. scutulatus venom previously reported and designated as type A venom (Glenn and Straight, 1978). Specimens with type A venom have been collected in California, Nevada, Utah and regions of Arizona. In addition to differences in lethal toxicity, the type B venom consistently exhibits a different protein profile, greater proteolytic activity, greater hemorrhagic activity and contains little or none of the major lethal toxin, Mojave toxin, compared to the type A venom. No external morphological characteristic could be found differentiating the type A venom specimens from the type B venom specimens. These findings further confirm the geographical variation of C. s. scutulatus venom in Arizona.

Animals↗

Studies on the pathogenesis of diet-induced dog gallstones.

Experimental diet-induced dog gallstones contained mainly protein, mucous substances, bile salts, bilirubin, an insoluble pigment which formed an insoluble black residue after acid hydrolysis, and only traces of cholesterol. Added dietary cholesterol was necessary to pigmented gallstone production and led to hypercholesterolemia. In bile, the ratio of cholesterol to bile salts was increased, but phospholipids were increased and cholesterol insolubility was not found. Dry weight, osmolality, and concentration of sodium and potassium in bile were reduced, but were not considered sufficient to influence micelle formation or lipid-pigment solubility. Taurine was reduced in serum and bile and unconjugated bile acids appeared in gallbladder bile; the pKa of these acids is near the pH of bile in these animals and may have caused precipitation of bile acids, accounting for their presence in the stones. Bile cultures were sterile. Total bilirubin content was unaltered but the methods used did not exclude the presence of unconjugated bilirubin as a potential cause of pigment precipitation in aqueous bile. Increased numbers of secretory vesicles occurred in gallbladder epithelium and large amounts of mucus were in the epithelial crypts. These observations suggest that bile proteins or mucous substances are important to lithogenesis in this model.

Amino Acids↗

Sudden toxicity of methadone in monkeys: behavioral and electrophysiological evidence.

A sudden and potentially lethal toxic reaction to a previously well-tolerated maintenance dose of methadone occurred in 4 of 6 monkeys. The reaction was characterized by gross behavioral and respiratory depression and a marked attenuation of both early and late components of the visual evoked response with an increase in most latencies. The nature of the evoked response alteration suggests a widespread central nervous system depressant effect of the drug during toxicity. Concomitant with the toxic reactions were dramatic increases in plasma methadone concentrations. Therefore the observed changes in sensitivity to methadone would appear to be the consequence of a sudden shift in pharmacokinetics resulting in toxic plasma concentrations.

Animals↗