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Biomedical subjects

W C Gordon

Publications and source records attributed to W C Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1990

Preferential uptake and metabolism of docosahexaenoic acid in membrane phospholipids from rod and cone photoreceptor cells of human and monkey retinas.

The uptake, metabolism, and cellular distribution of [3H]docosahexaenoic acid (DHA) in human and monkey retinas were studied with biochemical and autoradiographic techniques. In specimens from two human retina biopsies, incubated for 4 hr or 6 hr with [3H]docosahexaenoic acid (110 nM), 80% of the esterified [3H]fatty acid was recovered in phospholipids and the remainder in triacylglycerols and diacylglycerols. The distribution of [3H]DHA in individual phospholipids (PL) was similar in both retinas, with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accounting for most of the label. A similar labeling profile was observed in glycerolipids from monkey retina, and after 1 hr of incubation, high labeling of phosphatidic acid (PA, 11%) and phosphatidylinositol (PI, 20%) was observed. In both human and monkey retinas, a preferential uptake of [3H]DHA by photoreceptor cells was revealed by autoradiography. Cone photoreceptors showed a slightly higher density of silver grains in their inner segments than did rod photoreceptors. Photoreceptors accounted for 59% and 79% of the total [3H]DHA taken up by the human and monkey retinas, respectively, the remainder being distributed throughout the neural retina. In conclusion, this study shows for the first time that in human and monkey retinas, DHA is taken up with a high degree of selectivity by photoreceptor cells, and then becomes esterified mainly into phospholipids that will be subsequently utilized for the synthesis of new disc membranes.

Aged↗
PubMed1990

Light absorbed by 575-cones trigger rod disc shedding in the frog retina.

Photoreceptors periodically shed light-sensitive membranes; rods at light onset, cones at night. The spectral characteristics of light required to initiate shedding by 502-rods were studied in the frog retina. After 24 h of white light, animals were dark primed for 1 h then presented with 1 h of nearly monochromatic light to induce the shedding response. The light delivered a total photon flux of 2.5 or 0.5 microE/m2s. Following conventional fixation and plastic embedding, 1 micron sections were examined with light microscopy. The number of photoreceptor tips (phagosomes) shed by 100 consecutive rods were counted and plotted as a function of wavelength. Bright light induced at least 15 phagosomes per 100 rods at all wavelengths tested, 420-640 nm, and this shedding was more than doubled with light from 540-600 nm. When the light was dimmed, there was no shedding response except for this 540-600 nm window. This shedding peak closely corresponds to the absorbance curve of the frog's 575-cone photopigment and implies that the 575-cone can drive rod shedding. The broad background effect further indicates that all photoreceptors have an input and suggests that a luminosity cell, such as the internal horizontal cell, may be involved.

Animals↗
PubMed1990

Correlation between histological and behavioral measures of visual acuity in a zooplanktivorous fish, the white crappie (Pomoxis annularis).

Estimates of visual acuity in a pelagic freshwater zooplanktivorous fish, the white crappie (Pomoxis annularis, Centrarchidae), were made using a behavioral measure, the maximum observed prey pursuit distance (MxPD), and a histological measure, the density of cone cells in the retina. The greatest number of pursuits occurs in the 0-30 degrees wedge of the visual field; 87% of all pursuits occur in the first 40 degrees. The longest pursuits (200 mm) also occur in this area and generally get shorter from 0 to 180 degrees (from forward-directed) in the visual field. Consistent with the behavioral results, the largest number of cone photoreceptors (13,000/mm2) is found in the far temporal retina along the eye's horizontal meridian. Cone cell densities in the corresponding region of the nasal retina are approximately half this value. The number of cones decreases dorsally and ventrally from the horizontal meridian. Although the absolute values of visual acuity calculated from cone cell topography (i.e. MxPDs of 500 mm) are 2-3 times greater than those observed behaviorally (i.e. MxPDs of 200 mm), the trends in visual acuity across the visual field obtained from both measures are consistent. We suggest that overestimates of visual acuity obtained from cone cell counts alone result from this measure's not accounting for, among other properties of the nervous system, cone cell convergence onto ganglion cells and higher brain centers. Behavioral measures of visual acuity are, therefore, likely to yield a more accurate estimate of an animal's visual abilities.

Animals↗
PubMed1990

Docosahexaenoic acid utilization during rod photoreceptor cell renewal.

The supply of docosahexaenoic acid (22:6) to the frog retina, and its subsequent use by retinal cells, was studied by autoradiography and biochemical methods. Different delivery routes of 3H-22:6 were evaluated. Predominant uptake by the neural retina, mainly in ganglion cell axons, outer synaptic layer, and Müller cells, was observed when the radiolabeled fatty acid was given intravitreally or by short-term incubations of eyecups. In short-term eyecup incubations, Müller cells preferentially labeled, suggesting their involvement as a transient storage site. After intravenous or dorsal lymph sac injections of 3H-22:6, most of the retinal label was seen in rod photoreceptor cells. Two different labeling patterns were found in rod outer segments (ROS) as a function of postinjection time: an overall diffuse labeling pattern, as well as a dense-label region at the ROS base. This dense-label region expanded until it reached the apex of the ROS after about 30 d. HPLC analysis of fatty acid methyl esters from retinal lipid extracts showed that 3H-22:6 comprised essentially all of the label until after day 46, indicating lack of metabolic recycling of this molecule. Lipid-extracted retinal residue was devoid of radioactivity, demonstrating that protein did not contain significant covalently bound label. 3H-22:6 acylated to phospholipids in photoreceptor membranes moved apically, as evidenced by the expanding labeled region from the base of the ROS. Oil droplets in both the pigment epithelium and the cone photoreceptors labeled heavily, suggesting that 22:6 may be transiently stored. ROS tips that were phagocytosed by the pigment epithelium contained label similar in density to that of the outer segments, demonstrating that 22:6-phospholipids, at least in part, cycle through the pigment epithelial cells during visual cell renewal. In parallel experiments in frogs injected with 3H-leucine and maintained under the same experimental conditions, well-define, narrow protein bands were observed. Since the leading edge of the 3H-leucine-labeled band (rhodopsin), and that of the dense-label region of 3H-22:6 migrated at the same rate, reaching the rod tips at the same time, we suggest that the 3H-22:6-labeled phospholipids giving this profile are a unique molecular species noncovalently associated with rhodopsin.

Animals↗
PubMed1987

Tubocurarine chloride inhibits rod outer segment shedding in the frog retina.

The cholinergic postsynaptic neuromuscular blocker, tubocurarine chloride (curare), attenuates the rod shedding response of the frog in a dose-dependent manner. Injections of curare into the dorsal lymph sacs or intraocularly into the vitreous of the eye produced similar results. Intraocular injections of Ringer solution of varying quantities of 0.9% NaCl (the carrier solution of the commercially prepared curare), had no adverse effect on the shedding response. Additionally, injections of curare into one eye had no effect on the rod shedding rate of the other eye.

Animals↗
PubMed1984

Diagnostic efficacy of a new enzyme immunoassay for creatine kinase MB isoenzyme.

A new commercial enzyme immunoassay kit for quantification of creatine kinase-MB (CK-MB) isoenzyme was compared with its electrophoretic determination with respect to efficacy in diagnosis of acute myocardial infarction. Enzygnost CK-MB (Behring Diagnostics) is a solid-phase "sandwich"-type enzyme immunoassay with antibodies to the B-subunit coated on plastic tubes and peroxidase-conjugated antibodies to the M-subunit added after incubation with sample. This kit is designed to measure only CK-MB and not CK-MM, CK-BB, adenylate kinase, or atypical CK molecules. The linear-regression equation comparing the two methods was: Enzygnost = 0.98 . electrophoresis - 0.72, with a correlation coefficient of r = 0.967 (n = 143). For 51 patients admitted for diagnosis of possible acute myocardial infarction, the Enzygnost kit achieved 100% sensitivity, specificity, and efficiency in predicting the correct diagnosis. Corresponding values for the electrophoretic assay were: 95.5% sensitivity, 93.1% specificity, and 94.1% efficiency. We conclude that this kit method provides an excellent alternative to electrophoresis.

Clinical Enzyme Tests↗
PubMed1982

Local stimulation induces shedding throughout the frog retina.

Our previous work has demonstrated that rod shedding in the frog retina can be driven by environmental cues such as light onset. Although shedding normally occurs binocularly, we found that shedding could be initiated independently in either eye of the frog by monocular stimulation. Further, rod shedding occurs in vitro in the isolated eyecup under appropriate incubation conditions when provided with a light stimulus following a dark incubation period. Thus, the control mechanism for light induced rod shedding in the frog seems to be located within the eye, and does not seem to be systemically or centrally located. However, the exact link between light onset and shedding of the distal rod tips remains unknown. To elucidate further the control site for initiation of rod shedding, we used a variety of stimulus conditions, including front and rear screens as well as spots and slits projected directly on the retina, to stimulate a small portion of the frog retina with a range of light intensities and stimulus paradigms. In all cases where shedding occurred, it was uniform throughout the retina. Thus, it appears that the light-cued message received by a small population of photoreceptors is sufficient to initiate shedding throughout the retina. These results differ significantly from those found by Easter and Macy for light-induced photomechanical movements, which were found to be locally controlled.

Animals↗
PubMed1980

Specific immunoprophylaxis in experimental tumour-host systems.

A variety of animal species have been rendered resistant to syngeneic tumours of many histologic types of immunoprophylaxis. Among the types of preparation of tumour-associated antigens that have merit as vaccines are tumour cells treated with radiation, mitomycin C, certain viruses, neuraminidase, sulfhydryl blocking agents and lipoidal reagents. Alternatively, tumour-associated antigens of the cell membrane may be solubilized and used for vaccination. Recent studies with dimethyldioctadecylammonium bromide (DDA) indicate that it both modifies tumour cells and serves as an immunologic adjuvant in that it enhances protective responses to iodoacetamide-treated lymphoma cells and acts as a potent macrophage activator. By judicious application of DDA either delayed hypersensitivity or antibody response may be selectively enhanced. Several advantages of DDA over other adjuvants are its water solubility, the fact that it does not produce deleterious lesions at the site of injection and the fact that it eliminates the risk of systemic infection that exists with the use of live bacteria.

Adjuvants, Immunologic↗
PubMed1980

A new look at peripheral vascular disease in blacks: a two-year update.

A comprehensive overview of 66 patients-the majority of whom were black-undergoing distal lower extremity revascularization for severe atherosclerotic ischemia with impending limb loss is presented. Twenty-five patients are presently two-years postoperative, 19 are one-year post revascularization, and 22 are new additions having undergone revascularization within the last year.Patients in the study group are presented according to race, sex, and age. Their histories and pre-operative clinical conditions, along with angiographic and operative findings lead to the identification of a previously undescribed atherosclerotic phenomenon present among blacks. The impact of an aggressive program for limb salvage is reported and the prospect of avoiding needless limb loss is discussed.

Black or African American↗
PubMed1978

Effects of levamisole on normal and malignant murine lymphocytes.

Levamisole enhanced transformation of murine lymphocytes stimulated either by mitogens or allogeneic lymphocytes. In a similar dose-dependent pattern it stimulated in vitro growth of L1210, P1798, and 6C3HED but not YAC lymphoma cells. Stimulation of growth of lymphoma cells was greater by peritoneal cells harvested from normal mice 4 days after levamisole injection than by peritoneal cells from untreated mice. This effect correlated with the shortened survival time of BALB/c mice treated with levamisole prior to P1798 implantation compared to that of a control group not pretreated. Administration of levamisole with iodoacetamide-modified tumor cells in immunoprophylaxis studies had no effect on the rejection of a tumor implant or on development of tumor-specific antibody. Levamisole was added to regimens involving asparaginase therapy of 6C3HED-bearing C3H mice and chemoimmunotherapy of BALB/c mice bearing P1798 with methotrexate and iodoacetamide-modified P1798 cells. In neither case were there increased numbers of survivors, and mean survival time was generally decreased for the levamisole-treated groups. The stimulated tumor growth may have been mediated by a direct effect of levamisole on the lymphoma cells, through an effect on other cell types, or by both effects; these effects apparently outweighed potentially beneficial effects of levamisole on the immune system.

Animals↗
PubMed1978

Enhanced response to chemoimmunotherapy and immunoprophylaxis with the use of tumor-associated antigens with a lipophilic agent.

Treating iodoacetamide (IAD)-modified lymphoma cells with the lipophilic agent dimethyldioctadecylammonium bromide (DDA) increased their immunogenicity as evidenced by the increased capacity of syngeneic, vaccinated hosts to reject subsequent implants of the same lymphoma. Under conditions of suboptimal immunization to facilitate comparison, there were 61% survivors among mice challenged with tumor implants after immunization with modified cells and DDA compared to 20% survivors among those immunized in the absence of DDA. The enhanced immune response was dependent on DDA dosage and was most striking when DDA was directly complexed to the IAD-treated cells. DDA was also effective with solubilized tumor antigen and with lymphoma cells not pretreated with IAD, but the latter had to be heat killed to assure that they were nontumorigenic. In therapy experiments BALB/c mice bearing P1798 were treated with methotrexate followed by immunotherapy with IAD-P1798 alone or complexed to DDA. With two and three cycles of therapy, methotrexate alone yielded 5 and 13% survivors, while adding immunotherapy with the DDA complex gave survival rates of 63 and 71%. In the absence of DDA, chemoimmunotherapy with methotrexate and IAD-P1798 gave intermediate results. In the absence of antigen, DDA was ineffective in either immunoprophylaxis or therapy experiments.

Adjuvants, Immunologic↗
PubMed1977

Immunogenicity of solubilized tumor antigen extracted from P1798 murine lymphoma cells or isolated from tumor-bearer ascites fluid and reactivity with anti-thy-1.2 antiserum.

Solubilized antigen was prepared from P1798 lymphoma cells by sonication, 3 M KCI extraction, or isolated from the ascites fluid of syngeneic tumor-bearing BALB/c mice. Antigen was detected and quantitated by its ability to block activity of anti-P1798 serum raised in syngeneic mice, as assayed by cytotoxic and indirect immunofluorescence tests. It was established that the reaction was immunologically specific as the P1798 antigen did not inhibit the binding to L1210 lymphoma cells of antisera raised against L1210 in syngeneic DBA/2 or allogeneic BALB/c mice. Vaccination of BALB/c mice with different subcellular fractions of sonicated antigen or with ascites fluid resulted in protection against a live P1798 challenge with results comparable to those obtained using iodoacetamide-modified tumor cells. Solubilized antigen prepared by each of the three methods eluted from a Bio-Gel A5m agarose column exclusively in an early peak that had a molecular weight estimated to be greater than 2 X 10(6). This column-fractionated antigen was shown to cross-react with antiserum raised against Thy-1.2 antigen, which is present on P1798 cells. The purified P1798 antigen sedimented at 200,000 g and was shown to protect syngeneic mice in immunoprophylactic tests.

Animals↗