Biomedical subjects

R E Nordquist

Publications and source records attributed to R E Nordquist.

At least 19 recordsLinked to original sources

PubMed2006

In situ photoimmunotherapy: a tumour-directed treatment for melanoma.

We report a new immunological treatment for advanced cutaneous melanoma which combines laser stimulation with topical application of a toll-like receptor agonist. This treatment, in situ photoimmunotherapy (ISPI), provides an alternative to traditional therapies for melanoma patients with cutaneous metastases. A 6-week cycle of ISPI is carried out on cutaneous metastases located in a designated 20 x 20 cm treatment area: 2 weeks of pretreatment with twice-daily topical applications of imiquimod (5% cream under plastic occlusion), with a laser treatment session at week 2 and again at week 4. Topical imiquimod is continued for the entire 6-week cycle. Two patients with late-stage melanoma were treated with ISPI. Patient 1 had the primary tumour and local metastases on the left arm, as well as metastatic tumours in the lungs [American Joint Committee on Cancer (AJCC) stage IV]. Patient 2 had a head and neck melanoma with multiple local metastases (AJCC stage IIIC), which had failed repeated attempts at surgical resection and high-dose radiation therapy. Patient 1 is now free of all clinically detectable tumours (including the lung metastases) >20 months after the first treatment cycle. Patient 2 has been free of any clinical evidence of the tumour for over 6 months. These two cases demonstrate that ISPI can clear local tumour and trigger beneficial systemic responses, with a side-effect profile that compares favourably with other treatments for advanced melanoma.

Aged↗

PubMed2003

C-fos activation patterns in rat prefrontal cortex during acquisition of a cued classical conditioning task.

The prefrontal cortex (PFC) is known to be involved in associative learning; however, its specific role in acquisition of cued classical conditioning has not yet been determined. Furthermore, the role of regional differences within the PFC in the acquisition of cued conditioning is not well described. These issues were addressed by exposing rats to either one or four sessions of a cued classical conditioning task, and subsequently examining c-fos immunoreactivity in various areas of the PFC. Differences in patterns of c-fos immunopositive nuclei were found when comparing the PFC areas examined. No significant differences were found between rats presented with a temporally contingent conditioned stimulus (CS) light and food (paired groups) and those presented with the same stimuli temporally non-contingently (unpaired groups). In lateral and orbital PFC, both the paired and unpaired groups showed more c-fos immunopositive nuclei than control groups exposed only to the behavioral setup (context exposed groups), and all groups showed a drop in c-fos immunopositive nuclei from session 1 to session 4. In dorsal medial PFC, no differences were seen between the paired, unpaired and context exposed groups. These groups did, however, differ from naive animals, an effect that was not seen in the ventral medial PFC. The results of this study do not support a role for the PFC in the acquisition of a cued classical conditioning task. The differences seen between paired, unpaired and context exposed groups in orbital and lateral PFC could be due to contextual conditioning or reward-related effects.

Analysis of Variance↗

PubMed2001

Antitumor immunity induced by laser immunotherapy and its adoptive transfer.

The ideal cancer treatment modality should not only cause tumor regression and eradication but also induce a systemic antitumor immunity, which is essential for control of metastatic tumors and for long-term tumor resistance. Laser immunotherapy using a laser, a laser-absorbing dye, and an immunoadjuvant has induced such long-term immunity in treatment of a mammary metastatic tumor. The successfully treated rats established total resistance to multiple subsequent tumor challenges. To further study the mechanisms of the antitumor immunity induced by this novel treatment modality, passive adoptive transfer was performed using splenocytes as immune cells. The spleen cells that were harvested from successfully treated tumor-bearing rats provided 100% immunity in the naive recipients. The passively protected first cohort rats were immune to tumor challenge with an increased tumor dose; their splenocytes also prevented the establishment of tumor in the second cohort of naive recipient rats. This immunity transfer was accomplished without the usually required T-cell suppression in recipients.

Animals↗

PubMed2001

Ciprofloxacin microprecipitates and macroprecipitates in the human corneal epithelium.

In 4 corneal transplantation patients treated preoperatively with ciprofloxacin ophthalmic drops, microprecipitates associated with damaged corneal epithelium were noted in 2 patients. Another patient developed a large macroprecipitate in a corneal ulcer. All specimens were examined by electron microscopy and high-pressure liquid chromatography. The crystalline precipitates were pure ciprofloxacin. The macroprecipitate demonstrated a large zone of inhibition on agar plates seeded with a susceptible organism at 24 and 48 hours. It was bioactive and bioavailable in vitro.

Aged↗

PubMed1999

Long-term tumor resistance induced by laser photo-immunotherapy.

An ideal treatment modality for metastasizing tumors should eradicate the primary tumor and elicit a systemic, tumor-selective response leading to elimination of metastases and long-term tumor resistance. Also, it should be induced by local treatment at the primary site, to limit adverse systemic effects. A new method for treating metastatic tumors which utilizes a combination of a near-infrared laser, a photosensitizer and an immunoadjuvant has been developed. It involves intra-tumor injection of the sensitizer/adjuvant solution, followed by local non-invasive laser irradiation. It has produced regression and total eradication of treated primary tumors and untreated metastases at remote sites against mammary tumors in rats. Successfully treated tumor-bearing rats showed total tumor resistance to subsequent tumor rechallenge. Our histochemical results showed that sera from cured tumor-bearing rats contained antibodies that bound strongly to the plasma membrane of both living and preserved tumor cells. Western blot analysis of tumor cell proteins using sera from successfully treated rats as the source of primary antibodies also showed distinct bands, indicating induction of tumor-selective antibodies. Our findings indicate that a systemic, long-term effect on metastatic tumors can be induced by local application of laser photo-immunotherapy.

Adjuvants, Immunologic↗

PubMed1999

Measurement of x-ray attenuation coefficients of aqueous solutions of indocyanine green and glycated chitosan.

We report our experimental results of measurements of x-ray attenuation coefficients of aqueous solutions of a light absorbing dye, indocyanine green, and an immunoadjuvant, glycated chitosan. In the treatment of metastatic tumors in rats using a novel laser immunotherapy these solutions were administered in situ. The x-ray attenuation data of the solutions are essential to development of an x-ray digital imaging system for monitoring the administration of the solution, as well as for the distribution and the diffusion of the solution in tumors and in surrounding tissue. The composition of the solutions, the measurement system configuration, and the technique used to determine the attenuation coefficients are described. The experimental results show that glycated chitosan has a higher attenuation coefficient compared to indocyanine green and water. Our experimental data proved that, even at low concentrations, the x-ray attenuation through these aqueous solutions could be differentiated. Therefore, a digital x-ray imaging technique can be used effectively in monitoring and controlling the intratumor diffusion and distributions of these solutions.

Adjuvants, Immunologic↗

PubMed1998

Anatomy of mammalian conjunctival lymphoepithelium.

Ocular surface immune mechanisms are subservient to the fine function of the eye. A clear cornea with a smooth, well-lubricated facade is prerequisite to lucid vision. Hence, corneal inflammation and post-inflammatory scarring are intolerable, and the cornea contains a minimum of lymphoid elements. Although conjunctival dysfunction and consequent tear film deficiency can malign the corneal surface, conjunctival inflammation is tolerated to a considerable degree. In contrast to the human cornea, human conjunctiva contains an abundance of lymphoid tissue. Certain aspects of human conjunctival immunology elicit little debate. Langerhans cells are abundant in conjunctival epithelium. Isolated CD8+ suppressor/cytotoxic T cells predominate in conjunctival epithelium, while T cells in the substantia propria distribute equally between CD4+ T helper cells and CD8+ cells. Yet the presence of plasma cells in human conjunctiva, the expression of secretory component by human conjunctival epithelium, and the function of human conjunctival lymphoid follicles are in dispute. Confusion may derive in part from the use of inappropriate animal models; rodent conjunctiva does not appear to be a worthy facsimile for human conjunctiva. Discrepancies between different human studies likely result from variance in subject age, biopsy site and extent, histologic or histochemical technique, and perhaps the degree of inflammation present at the time of biopsy. Careful immunohistochemical and in situ molecular assays on well-defined loci within the conjunctiva of comparable human subjects may resolve such questions in the future. Organized mucosa-associated lymphoid tissue is rigorously defined as mucosal lymphoid follicles with an ultrastructurally distinct overlying lymphoepithelium. Based on available evidence, the epithelium overlying mammalian conjunctival lymphoid follicles does not contain distinct M cells. Whether zonal differences in morphology reflect real differences in the capacity to sample tear film antigens for presentation to the mucosal immune system remains to be established.

Animals↗

PubMed1997

Laser-photosensitizer assisted immunotherapy: a novel modality for cancer treatment.

Photosensitizer-enhanced laser treatment, where dyes are activated in situ by lasers of appropriate wavelengths, provides highly selective tissue destruction, both spatially and temporally, through photophysical reactions. Although laser-sensitizer treatment for cancer can achieve a controlled local tumor cell destruction on a large scale, total tumor eradication may not be accomplished because of the incomplete local tumor killing or the presence of tumor metastases, or both. The long-term control of cancer depends on the host immune surveillance and defense systems in which both cell-mediated and humoral responses are critical. In this study we report a novel minimally invasive cancer treatment combining the laser photophysical effects with the photobiological effects. Irradiation of a rat mammary tumor by an 805 nm diode laser, after an intratumor administration of a specific photosensitizer, indocyanine green in a glycated chitosan gel, caused immediate photothermal destruction of neoplastic cells. Concomitantly this treatment stimulated the immunological defense system against residual and metastatic tumor cells. Increases in survival rate and in the eradication of tumor burden, both primary and metastatic, were observed after this treatment. Furthermore, the resistance of successfully treated rats to tumor rechallenge demonstrated a long-lasting systemic effect of the treatment. These findings indicate that our treatment has triggered a specific humoral immune response in the tumor-bearing rats.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Effect of resin/fluoride and holmium:YAG laser irradiation on the resistance to the formation of caries-like lesions.

PURPOSE: This study compared the effects of a combination of a topical application of resin/NaF mixture and holmium-doped yttrium aluminum garnet (HO:YAG) laser energy with untreated control sites for their resistance to acid destruction/mechanical challenges of root surfaces adjacent to restorative margins. MATERIALS AND METHODS: Forty-eight extracted human teeth were prepared for restorations with coronal margins in enamel and the apical margins on root surfaces. Four types of restorative materials were used. One half of the restorative/root surface margins were treated with an application of nonfilled resin/fluoride mixture and holmium-doped yttrium aluminum garnet laser irradiation; the remaining portion served as the untreated control for each tooth. Acid (10% formic) and mechanical (air sandblaster) challenges were used to test the effects of these treated sites to their controls and to other types of restorative/root surface margins. The depth of root surface loss within 0 to 2 mm apical from the restorative margins was measured and evaluated after 24, 48, and 72 hours of acid exposures. RESULTS: The measurements of tooth loss for the 24- and 48-hour acid-exposure cycles were subjected to statistical analysis (ANOVA) using a paired t test for the variables. The variables, depth of tooth surface loss for the control sites was compared with the depth of loss of the treated sites on opposing sides of each tooth. The depth of tooth surface loss for the control sites had an average mean of 0.35 (0.25) mm for the 24-hour acid exposures, with the opposing treated sides having a mean of 0.053 (0.05) mm (significant at the 0.05 level). The 48-hour acid-exposure results showed significant increased tooth loss for the control sites, but minimum additional loss on the treated sites. The control sites showed an average mean of 1.16 (0.24) mm and a mean of 0.095 (0.103) mm for the treated areas, significant at the 0.05 level. No measurements were made for the 72-hour cycle groups of composite and amalgam alloy restorations because of the loss of most of the filling materials in the control sites. The control groups of crowns showed an average mean loss of 2.06 (0.37) mm with only 0.20 (0.19) mm surface loss for the treated sites. The paired t test for variables indicated no significant differences of tooth surface loss between various types of restorative margins used in this study. CONCLUSIONS: HO:YAG laser energy irradiation after application of resin/NaF to restorative margins and adjacent areas showed a significant increased resistance to acid/mechanical destruction on cementum-dentin root surfaces. The integrity of the restorative/dentin margins were maintained after extended exposures to formic acid and mechanical challenges.

Composite Resins↗

PubMed1996

Use of the holmium yttrium aluminum garnet laser for percutaneous thoracolumbar intervertebral disk ablation in dogs.

OBJECTIVE-To evaluate a laser ablation-technique for treatment of thoracolumbar intervertebral disk disease in dogs. DESIGN-Prospective case series. ANIMALS-33 dogs with signs of recurrent back pain associated with intervertebral disk disease after the initial episode had been managed conservatively for a minimum of 2 weeks. PROCEDURE-Spinal needles were placed percutaneously through the annulus fibroses to permit delivery of an optical fiber into the nucleus pulposes of thoracolumbar intervertebral disks T10-11 through L3-4. Fluoroscopy was used to guide needle placement. Holmium yttrium aluminum garnet laser energy then was used to ablate the contents of each selected intervertebral disk. Intervals from time of treatment to time of assessment ranged from 3 to 114 weeks. RESULTS-All dogs recovered without complication. Results of follow-up radiography and histologic evaluation indicated that percutaneous holmium yttrium aluminum garnet laser ablation reduces the volume of nucleus pulposus in treated disks. CLINICAL IMPLICATIONS-Used as a clinical treatment and prophylactically, this minimally invasive procedure should prevent further extrusion of partially herniated disks and should reduce the chances of subsequent herniation of disks at other treatment sites.

Animals↗

PubMed1996

Photothermal effects on murine mammary tumors using indocyanine green and an 808-nm diode laser: an in vivo efficacy study.

Murine mammary tumors were treated using indocyanine green and an 808 nm diode laser, and the in vivo chromophore-enhanced photothermal effects on the tumor burden and on tumor rat survival were investigated. The power of the laser was selected in the range of 5-10 W, and irradiation duration 3-5 min. One percent aqueous indocyanine green solution in a volume of 100-200 microliters was administered in situ, either acutely or 24 h prior to the treatment. The photothermal interaction was apparent under all our treatment conditions with a well-defined spatial containment in this study and the tumor growth was slowed after treatment. The post-treatment observation showed tumor recurrence and metastasis; no long-term survival was achieved with the single application of laser in conjunction with indocyanine green. Our results pose a question on the efficacy of the photothermal interaction even though tumor cell destruction can be achieved in a large and controlled scale. However, this highly selective photothermal impact on the tumor tissue did suggest that this method be applied repeatedly to be more effective and be used as the precursor of other modalities, such as chemotherapy, radiation therapy, immunotherapy, and surgery.

Animals↗

PubMed1995

Chromophore-enhanced in vivo tumor cell destruction using an 808-nm diode laser.

Rat mammary tumors were treated using an 808-nm diode laser in a power range of 3-15 W. Photothermolysis was selectively enhanced by the chromophore indocyanine green (ICG), which has an absorption peak corresponding to the laser wavelength. ICG, injected into neoplastic tissues 24 h before laser exposure, was retained in sufficient quantity to produce a strong photothermal reaction. With appropriate laser power and adequate irradiation duration, laser energy could inflict severe photothermal damage to the entire targeted tumor tissue while leaving the skin and other interdicted tissue undamaged. Higher laser powers (10-15 W) produced more surface damage that limited light transmission and as a result gave rise to reduced regions of thermal destruction. Post-treatment observation revealed the survival of numerous tumor cells. This finding questions the long term efficacy of the photothermal effect of a single treatment using the combination of the ICG and the diode laser, particularly in the absence of other modalities.

Animals↗

PubMed1995

Chromophore-enhanced laser-tumor tissue photothermal interaction using an 808-nm diode laser.

A diode laser was used to irradiate tumor tissue, with indocyanine green as the chromophore. The 808-nm wavelength radiation falls within the absorption peak of the chromophore (about 780 nm). The preliminary results in this report revealed clear and significant coupling of this laser and indocyanine green in laser-tissue photothermal interaction. The chromophore targeted tissue showed laser damage while peripheral tissues remained intact. Without the chromophore, this laser inflicted no apparent tissue damage in the non-contact mode with irradiance up to 1755 J/cm2.

Animals↗

PubMed1995

Immunological mimicry between retinal S-antigen and group A streptococcal M proteins.

Immunological mimicry between host and microbial proteins has been suggested as a potential mechanism in the development of uveitis in humans. In this study immunological crossreactivity between anti-streptococcal monoclonal antibodies (MAbs) and the human eye was investigated. In indirect immunofluorescence, we demonstrated novel immunological crossreactivity of two anti-streptococcal MAbs (27 and 112) with the rod outer (and inner) segments of the retina of the human eye. In further studies, retinal S-Ag, a uveitogenic protein in the rod outer (and inner) segments, was found to react with the anti-streptococcal MAbs. In addition, several uveitogenic peptides of S-Ag were recognized by the anti-streptococcal MAbs. In the ELISA and Western immunoblot, anti-S-Ag MAbs crossreacted with group A streptococci and the streptococcal M protein further demonstrating sites of antigenic similarity. Homology between the retinal S-Ag and streptococcal M protein was observed in amino acid sequences repeated in the B repeat region of the streptococcal M5 protein. These data show that retinal S-antigen has immunological similarities with streptococcal M protein, a major virulence determinant and strong bacterial cell surface antigen.

Amino Acid Sequence↗

PubMed1995

The role of free radicals in paraquat-induced corneal lesions.

Paraquat is a synthetic bipyridylium salt widely used as herbicide and defoliant. Enzyme-catalyzed redoxcycling of paraquat generates oxygen radicals. The toxic, even lethal, effects of paraquat are due to free radical-mediated tissue injury. Ocular lesions, sometimes quite severe, have been observed following accidental splashing of paraquat solutions onto the eyes. These studies were designed to document the generation of paraquat free radicals in corneal tissue, and to describe the histological nature of the corneal injuries in experimental animals (rabbits and monkeys). The EPR spectrum of rabbit corneas, 30 min. after intrastromal injection of paraquat, showed the signal of the free radical of paraquat. Ultrastructural studies of corneas 8 days after intrastromal injections (100 microliters) of paraquat solutions showed that the initial lesions occur at the epithelium/basement membrane interface. In rabbit cornea, dose dependent lesions were observed, i.e. whereas 50 mM paraquat caused only minimal damage to the epithelial basement membrane, 75 mM caused complete dissolution to the basement membrane with some damage to stromal collagen, and loss of epithelium with stromal ulceration and severe inflammatory response were observed with 150 mM paraquat. Monkey corneas were less susceptible than those of rabbits to the effects of paraquat. No lesions were observed following intrastromal injections of 50 mM or 75 mM paraquat. With higher concentrations of paraquat (100 mM and 150 mM) the primary injuries were to the proximal and lateral plasma membranes of basal epithelial cells; basement membrane alterations were detected only adjacent to areas of significant plasma membrane damage. The underlying Bowman's membrane and stroma were not affected. Anatomical differences between the corneas of rabbit and monkeys as well as possible biochemical differences may account for the species differences observed.

Animals↗

PubMed1995

Evaluation of the potential of a polylactic acid barrier for correction of periodontal defects in baboons: a clinical and histologic study.

Created periodontal defects in baboons were treated with one of four possible treatment modes: (1) root preparation and Epi-Guide biodegradable polylactic acid barrier, (2) root preparation and Gore-Tex e-PTFE membrane, (3) root preparation only (no barrier), and (4) no root preparation and no barrier (control). Root preparation consisted of hand instrumentation and use of finishing burs. Measurements of gingival recession were recorded from color photographic slides taken weekly for 6 weeks following barrier placement. Block sections were removed from one animal 6 weeks after barrier placement and prepared for histologic evaluation. Significantly more gingival recession was observed at the Gore-Tex sites than at the Epi-Guide sites. There were no significant differences in gingival recession between the Epi-Guide sites and root preparation-only sites or control sites. Both types of barriers were histologically acceptable. At 6 weeks, the Epi-Guide material was present histologically in a partially resorbed state. There was a mild inflammatory reaction in the surrounding connective tissues.

Alveolar Bone Loss↗

PubMed1992

Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmitis.

The contribution of the pAD1-encoded cytolysin to Enterococcus faecalis virulence in an experimental endophthalmitis model was studied by using isogenic strains differing only in the location of transposon Tn917. The course of experimental endophthalmitis in New Zealand White rabbits was evaluated by postoperative reduction in retinal neuroresponsiveness, thin-section histopathology, and transmission electron microscopy. Infections caused by cytolytic E. faecalis resulted in 99% loss of retinal function at postoperative day 3, while isogenic, noncytolytic strains produced reductions of only 74.2%. Light microscopy revealed near-total destruction of retinal architecture at 24 h postinfection with cytolytic E. faecalis, while noncytolytic strains produced few or no destructive changes. Transmission electron microscopy revealed tissue destruction in retinal layers as early as 6 h postinfection with cytolytic E. faecalis. In vivo and in vitro growth rates of cytolytic and noncytolytic E. faecalis showed similar kinetics. These data demonstrate the contribution of the pAD1-encoded cytolysin to both the course and the severity of experimental E. faecalis endophthalmitis.

Animals↗

PubMed1991

The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates.

Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta-mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross-linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus.

Animals↗