Biomedical subjects

R C Straight

Publications and source records attributed to R C Straight.

At least 19 recordsLinked to original sources

PubMed1992

Photodynamic therapy of human ovarian epithelial carcinoma, OVCAR-3, heterotransplanted in the nude mouse.

OBJECTIVE: Our objective was to develop an animal model for the study of photodynamic therapy in the treatment of human ovarian epithelial carcinoma. STUDY DESIGN: The human ovarian carcinoma OVCAR-3 was heterotransplanted into nude, athymic mice and treated with photodynamic therapy consisting of the hematoporphyrin derivative Photofrin II 10 ng/kg and argon-pumped dye laser light at 630 nm (200 J/cm2). Growth of tumors on one side of seven mice (treated tumors, n = 7) was compared with contralateral tumors (control tumors, n = 8) not exposed to laser. Hematoporphyrin derivative uptake was determined in tumor and other tissues. RESULTS: Photodynamically treated tumors were completely ablated, and all remained absent. Hematoporphyrin derivative uptake was nonselective for tumor compared with other tissues. CONCLUSION: This model provides reproducible parameters for the study of photodynamic therapy in the treatment of gynecologic malignancies and demonstrates the need for methods to increase selective uptake of hematoporphyrin derivatives.

Animals↗

PubMed1992

North-south regional variation in phospholipase A activity in the venom of Crotalus ruber.

1. Twenty-seven individual venoms from the rattlesnake species Crotalus ruber from different regions were comparatively analyzed by reverse-phase HPLC and analyzed for phospholipase A (PLA) content using a polarographic assay. 2. Two fractions containing PLA activity were detected by HPLC in the venoms of all the C. ruber specimens from southern Baja, Mexico, but specimens from southern California, U.S.A., were lacking corresponding fractions and were extremely low or lacking in PLA activity in their venoms. 3. The north-south regional variation in PLA content in C. ruber venom does not correlate with the north-south ranges (based on external morphology) of the subspecies C. ruber ruber and C. ruber lucasensis.

Animals↗

PubMed1992

Effects of photodynamic therapy in combination with intravesical drugs in a murine bladder tumor model.

This study was designed to evaluate the interaction of photodynamic therapy (PDT) and intravesical drugs (thiotepa, adriamycin, mitomycin C and BCG) in a murine transitional cell carcinoma (MBT-2) model. C3H/He mice with implanted MBT-2 flank tumors were treated with either thiotepa (TT), adriamycin (ADM), mitomycin C, Bacillus Calmette-Guerin (BCG), photodynamic therapy (PDT) or a combination of the drug and PDT. The MBT-2 tumor showed sensitivity to adriamycin, MMC or PDT compared to control. PDT combined with either adriamycin, MMC or BCG, produced a greater retardation in the growth of the MBT-2 tumor than monotherapy with adriamycin, MMC, BCG or PDT. PDT combined with the anticancer agents currently used in intravesical therapy for bladder cancer is well tolerated. The combination of PDT and intravesical drugs may enhance the tumoricidal effect of either treatment used alone.

Administration, Intravesical↗

PubMed1991

Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative.

Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390-436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer.

1,2-Dimethylhydrazine↗

PubMed1991

Regional differences in content of small basic peptide toxins in the venoms of Crotalus adamanteus and Crotalus horridus.

1. Reverse-phase HPLC and organic solvents were used to isolate small basic peptide (SBP) toxins from the venoms of Crotalus adamanteus, C. durissus terrificus, C. horridus, C. scutulatus scutulatus, C. viridis concolor, C. viridis helleri and C. viridis viridis. 2. Acid-DEP analyses indicated a high degree of toxin purity which was obtained with a single HPLC run. 3. The combined results of HPLC, immunodiffusion and electrophoresis analyses of venoms from different geographical regions indicate that the SBP toxin content in the venoms of Crotalus adamanteus, Crotalus horridus, Crotalus scutulatus and Crotalus viridis viridis may vary regionally.

Animals↗

PubMed1991

Application of charge-coupled device technology for measurement of laser light and fluorescence distribution in tumors for photodynamic therapy.

Laser and fluorescence light distributions with applications for photodynamic therapy were measured in mouse tumors using a non-invasive electronic optical imaging system. The system consists of a liquid-nitrogen-cooled, charge-coupled-device (CCD) array camera under computer control with 576 x 384 detection elements having dimensions of 23 microns x 23 microns. The available dynamic range of the array is approx. 10(3), and the effective wavelength range is 400-1000 nm. An interstitially placed cylindrical diffusing optical fiber was used to provide tumor illumination. The light distribution pattern from the fiber was determined by immersing the cylindrical diffusing tip in a fluorescing solution and recording the emission image. Fluorescence imaging facilitates an accurate measurement of light intensity distribution while avoiding problems associated with the directional nature of other detection methods used with diffusing fibers. Radiation-induced fibrosarcoma tumors on C3H mice were grown to about 1 cm diameter for in vivo recording of light distribution from the tumor volume and for determination of effective light penetration distance at 18 wavelengths in the range 458-995 nm. Endogenous tumor fluorescence and Photofrin II fluorescence intensity were measured over the wavelength range 585-725 nm to investigate the possible application of CCD imaging technology for drug distribution measurements. Model experiments were begun to evaluate the relative importance of potential distortions of light distribution measurements using this approach.

Animals↗

PubMed1990

Laser photodynamic therapy for papilloma viral lesions.

Photodynamic therapy was tested for its therapeutic efficacy in eradicating rabbit papilloma warts. The wild-type viral warts suspension was used to induce treatable papilloma warts in the cutaneous tissue of Dutch Belted rabbits. The photosensitizing agents used intravenously were Photofrin II at 10 mg/kg of body weight and Chlorin e6 monoethylene diamine monohydrochloric acid (Chlorin e6 med HCl) at 1 mg/kg of body weight. The lasers used were an argon-dye laser at 628 and 655 nm and a gold vapor laser at 628 nm. The irradiances of 25 to 180 mW/cm2 were applied topically with an end-on lens optical fiber with total radiant doses of 7.5 to 54 J/cm2. Photofrin II and the argon-dye laser at the highest light dosage (54 J/cm2) and Chlorin e6 monoethylene diamine monohydrochloride administered 2 hours before argon-dye laser irradiation at 655 nm at the highest light dosage (54 J/cm2) produced wart regression. Total wart regression without recurrence was achieved with Photofrin II and the gold vapor laser at all light dosages. The difference observed between the argon-dye laser and the gold vapor laser might be explained by the pulsed nature of the gold vapor laser, with its high-peak powers, some 5000 x the average measured light dose. In this model, the smaller, less cornified lesions were more effectively treated with photodynamic therapy.

Animals↗

PubMed1990

Intraoperative phototherapy (PDT) and surgical resection in a mouse neuroblastoma model.

This study evaluates the effect of intraoperative photodynamic therapy (PDT) using the multiline argon laser (488-514 nm) or the argon-dye laser (630 nm) combined with surgical resection compared with surgical resection alone in reducing the incidence of C1300 neuroblastoma recurrence in mice. In the control groups, surgical resection alone resulted in 86% +/- 12% tumor recurrence. Surgical resection and intraoperative lasing without photosensitizer resulted in 75% +/- 27% tumor recurrence with the argon-dye laser and 55% +/- 18% recurrence with the multiline argon laser. In the treatment groups, surgical resection and intraoperative PDT at 630 nm resulted in 56% +/- 19% tumor recurrence whereas surgical resection and intraoperative PDT at 488-514 nm resulted in 21% +/- 7% tumor recurrence. The cause for the decrease in local recurrence in the control group using the multiline argon laser is unknown, but could it be due in part to hyperthermic effects. Intraoperative PDT was an effective adjunct to surgical resection in preventing local recurrence in this tumor model.

Animals↗

PubMed1990

Regional variation of biochemical characteristics and antigeneity in Great Basin rattlesnake (Crotalus viridis lutosus) venom.

1. Three pooled and 20 individual venom samples of Crotalus viridis lutosus from different localities in Utah and Arizona were screened and fractionated with HPLC-anion exchange. 2. Pooled venom samples and fractions were tested for hemorrhagic, collagenase, and phospholipase activities, and reactivity to a monoclonal antibody against a hemorrhagin from C. atrox venom (CA-P-8) using ELISA. 3. The 20 individual samples were organized into four groups based on their HPLC profiles. 4. ELISA results and specific hemorrhagic activity of the venom samples displayed a variation in latitidinal distribution although from the same species.

Animals↗

PubMed1990

Venom characteristics as an indicator of hybridization between Crotalus viridis viridis and Crotalus scutulatus scutulatus in New Mexico.

One hundred and thirteen venoms from 46 populations of Crotalus viridis viridis were screened by immunodiffusion for protein toxins antigenically similar to the phospholipase A2 (PLA) toxin 'Mojave toxin', using a polyclonal antibody to it's basic PLA subunit. Venom i.p. LD50 values in mice were recorded from 22 of the 46 populations. The venoms of three of 14 specimens from southwest (S.W.) New Mexico and one specimen from northern Arizona were immunologically positive by the immunodiffusion tests and produced low LD50 values (0.38-0.65 mg/kg) compared to all immunologically negative venoms (0.9-5.5 mg/kg). These four specimens were morphologically typical for C. v. viridis and their venoms were the only samples of 15 southern New Mexico specimens examined by reverse phase HPLC to exhibit peaks corresponding to the acidic and basic subunits of Mojave toxin. Alkaline polyacrylamide gel electrophoresis (PAGE) analysis of the recombined subunit peaks from the C.v. viridis venom from the S.W. New Mexico specimens showed more similarity to Mojave toxin from C.s. scutulatus venom than to similar toxins in C.v. concolor venom. The combined results of the immunodiffusion, lethal toxicity tests, HPLC profiles and PAGE analysis strongly suggest that the venoms of the three New Mexico specimens contain Mojave toxin(s), as a result of some previous hybridization with C.s. scutulatus. The northern Arizona specimen likely contains 'concolor toxin' through integration with C.v. concolor in its' genetic background.

Animals↗

PubMed1989

Photofrin II localization in rat cecum.

Laser excitation of photodynamic agents localizing in colonic tumors may allow the early diagnosis and treatment of colon cancer. The efficacy of these agents requires a high ratio of tumor to background photosensitizer accumulation and fluorescence. To assess normal colonic background fluorescence and hematoporphyrin accumulation 31 rats were studied after an intravenous injection of Photofrin II (PF-II) at a dose of 5 mg/kg. An increase in mucosal fluorescence and porphyrin content was noted in the cecum 24 hours after injection. Cecal accumulation of PF-II may affect its efficacy in the localization and treatment of cecal tumors. Further investigation into the mechanism and clinical significance of this finding is needed.

Animals↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗