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S L Mills

Publications and source records attributed to S L Mills.

54 records · Page 3Linked to original sources
PubMed1987

Researches on a unilaterally blue-blinded rhesus monkey.

Psychophysical measures of hue (wavelength) discrimination and spectral sensitivity were collected over a 3-year-period on a rhesus monkey whose right eye had been exposed to intense blue light 10 years prior and had shown a pronounced loss of blue sensitivity in an increment-threshold, spectral-sensitivity task. Hue discrimination, to a somewhat greater degree than spectral sensitivity, revealed large differences between the normal and blue-exposed eye. The difference limens were in some cases 100 nm for the blue-exposed eye compared to 10-15 nm for the normal eye. The hue-discrimination functions from the blue-exposed eye were similar in form to those from human tritanopes (blue-blind humans), and those from the monkey's normal eye were similar to those from normal humans. Detailed functions, where the variable wavelength was shorter as opposed to longer than the reference wavelength, were shown separately for each of the monkey's eyes; those from the blue-exposed eye were very similar to analogous functions from the one case where they have been shown separately for a human tritanope.

Animals↗
PubMed1986

Immunochemical aspects of monoclonal antibodies important for radiopharmaceutical development.

Successful development of radiopharmaceuticals from monoclonal antibodies will require the control of several immunochemical aspects of the antibody molecules. A proposed set of methods is presented here for evaluating these immunochemical parameters. This approach consists of monitoring each monoclonal antibody harvest by selective affinity chromatography to determine the presence of detectable alterations in molecular homogeneity. The products are then evaluated by radioimmunoassay technique standardized for total immunoglobulin immunoreactivity. These assays are utilized to detect variation in the immunoreactivity secondary to changes in the hybridoma cell lines, and to measure any detectable denaturation secondary to purification, fragment production and radiolabeling. HPLC molecular sieving chromatography is presented as a practical and informative monitor of molecular stability of these radiopharmaceuticals in vitro and in vivo.

Antibodies, Monoclonal↗
PubMed1986

123I radiolabeling of monoclonal antibodies for in vivo procedures.

When labeled to monoclonal antibodies (MAbs) or their fragments, 123I can be used for imaging or for predicting the treatment potential and radiation dosimetry of 131I labeled to the same molecular species. Because 123I (p,5n) from the Crocker Nuclear Laboratory is in dilute solution, when compared with commercial 125I of labeling grade, we have evaluated labeling parameters using Chloramine-T as the oxidant and derived an optimum set of labeling conditions that provide a 60-80% radiochemical yield of highly immunoreactive antibody. When Lym-1, an IgG-2a murine antibody against human lymphoma, was used, yields of labeled immunoglobulin were decreased by protein or Chloramine-T concentrations less than 0.4 microgram/microliter and 0.8 microgram/microliter, respectively; denaturation of the immunoglobulin occurred when the Chloramine-T concentration was greater than 1.0 microgram/microliter. Optimum labeling occurred at pH 7-8 with deleterious effects when the pH was below 5 or above 10. An optimum method for labeling antibodies with multimillicurie amounts of 123I (less than one iodine atom per 100 antibody molecules) is described. Some of the observations derived from this study are also applicable to the preparation of treatment doses of 131I-labeled antibodies, wherein the amount of antibody can be a restrictive factor.

Antibodies, Monoclonal↗
PubMedDate not supplied

Distribution and coverage of A- and B-type horizontal cells stained with Neurobiotin in the rabbit retina.

Both A- and B-type horizontal cells in the rabbit retina were labeled by brief in vitro incubations of the isolated retina in the blue fluorescent dye 4,6-diamino-2-phenylindole. Intracellular injection of Lucifer Yellow into the somata revealed the morphology of the individual cells. Dye-coupling with Lucifer Yellow was seen only between A-type horizontal cells. By contrast, injection of the tracer Neurobiotin showed dye-coupling between both A- and B-type horizontal cells. There also appeared to be coupling between the axon terminals of B-type horizontal cells. The extensive dye-coupling seen following injection of Neurobiotin into a single horizontal cell soma can be used to obtain population counts of each cell type. Staining of large numbers of each cell type across the retina showed that each type increased in number and declined in dendritic diameter as the visual streak was approached, such that relatively constant coverage across the retina was maintained. In the visual streak, A-type horizontal cells numbered 555 cells/mm2 and averaged 120 microns in diameter, compared to 1375 cells/mm2 and 100 microns for B-type horizontal cells. In the periphery, the A- and B-types numbered 250 cells/mm2 and 400 cells/mm2, respectively. The average diameters of the dendritic trees at these locations were 225 microns for the A-type and 175 microns for the B-type. Coverage across the retina averaged almost six for A-type horizontal cells and 8-10 for the B-type. A-type horizontal cells in the visual streak whose elliptical dendritic fields were shown by Bloomfield (1992) to correlate physiologically with orientation bias were shown to be dye-coupled to cells with symmetrical dendritic fields.

Animals↗
PubMedDate not supplied

Red-green interactions in the spectral sensitivity of primates as derived from ERG and behavioral data.

Different techniques were used to manipulate the inhibitory interaction between the red and green photoreceptors (R and G cones) of rhesus and human primates. The response techniques that were used were the corneal electroretinogram (ERG) and psychophysical increment-threshold spectral sensitivity functions. Red-green opponency, as measured by the depth of the notch at 580 nm, is removed by intravitreal injection of bicuculline but not by strychnine. Therefore, red-green opponency is mediated by GABA and not glycine. The depth of the notch is dependent upon stimulus size. Between 30' and 15' test light diameters, this sign of red-green opponency disappears. Psychophysical increment thresholds are shown to produce the notch while decrements do not and intravitreal APB is shown to reduce the notch, evidence that red-green opponency is carried by the "ON" and not the "OFF" bipolar pathways of the retina. Red and green annuli are shown to selectively reduce red and green inhibition, as though there were selective reduction of the surround response in center-surround organized red-green receptive fields.

Aminobutyrates↗
PubMedDate not supplied

Dye coupling in horizontal cells of developing rabbit retina.

In the mature rabbit retina, two classes of horizontal cells, A type and B type, provide lateral inhibition in the outer plexiform layer (OPL) and spatially modify the activation of bipolar cells by photoreceptors. Gap junctions connecting homologous horizontal cells determine the extent to which this inhibitory activity spreads laterally across the OPL. Little is currently known about the expression of gap junctions in horizontal cells during postnatal development or how cell-cell coupling might contribute to subsequent maturational events. We have examined the morphological attributes and coupling properties of developing A and B type horizontal cells in neonatal rabbit retina using intracellular injections of Lucifer Yellow and Neurobiotin. Prelabeling with DAPI permitted the targeting of horizontal cell bodies for intracellular injection in perfused preparations of isolated retina. A and B type horizontal cells were identifiable at birth although their dendritic field sizes had not reached adult proportions and their synaptic contacts in the OPL were minimal. Both cell types exhibited homologous dye coupling at birth. Similar to that seen in the adult, no heterologous coupling was observed, and homologous coupling among A type cells was stronger than that observed among B type cells. The spread of tracer compounds through gap junctions of morphologically immature horizontal cells suggests that ions and other small, bioactive compounds may likewise spread through coupled, horizontal networks to coordinate the subsequent maturational of emerging outer plexiform layer pathways.

Animals↗
PubMedDate not supplied

The kinetics of tracer movement through homologous gap junctions in the rabbit retina.

Observation of the spread of biotinylated or fluorescent tracers following injection into a single cell has become one of the most common methods of demonstrating the presence of gap junctions. Nevertheless, many of the fundamental features of tracer movement through gap junctions are still poorly understood. These include the relative roles of diffusion and iontophoretic current, and under what conditions the size of the stained mosaic will increase, asymptote, or decline. Additionally, the effect of variations in amount of tracer introduced, as produced by variation in electrode resistance following cell penetration, is not obvious. To examine these questions, Neurobiotin was microinjected into the two types of horizontal cell of the rabbit retina and visualized with streptavidin-Cy3. Images were digitally captured using a confocal microscope. The spatial distribution of Neurobiotin across the patches of coupled cells was measured. Adequate fits to the data were obtained by fitting to a model with terms for diffusion and amount of tracer injected. Results indicated that passive diffusion is the major source of tracer movement through gap junctions, whereas iontophoretic current played no role over the range tested. Fluorescent visualization, although slightly less sensitive than peroxidase reactions, produced staining intensities with a more useful dynamic range. The rate constants for movement of Neurobiotin between A-type horizontal cells was about ten times greater than that for B-type horizontal cells. Although direct extrapolation to ion conductances cannot be assumed, tracer movement can be used to give an estimate of relative coupling rates across cell types, retinal location, or modulation conditions in intact tissue.

Animals↗
PubMedDate not supplied

Localization of nitric oxide synthase, NADPH diaphorase and soluble guanylyl cyclase in adult rabbit retina.

Nitric oxide (NO) acts as a neuronal messenger which activates soluble guanylyl cyclase (SGC) in neighboring cells and produces a wide range of physiological effects in the central nervous system (CNS). Using immunocytochemical and histochemical stains, we have characterized the NO/SGC system in the rabbit retina and to a lesser extent, in monkey retina. Based on staining patterns observed with an antibody to nitric oxide synthase (NOS) type I and a histochemical marker for NADPH diaphorase, a metabolic intermediate required for NOS activity, three major classes of neurons appear to generate NO in the rabbit retina. These include two subclasses of sparsely distributed wide field amacrine cells, rod and cone photoreceptors, and a subpopulation of ganglion cells. Equivalent cell populations were labeled in monkey retina. An antibody to SGC (tested only in rabbit retina), labeled large arrays of cone photoreceptors in the outer nuclear layer, both amacrine and bipolar cells in the inner nuclear layer (INL), as well as populations of neurons in the ganglion cell layer. These data suggest that the ability to generate NO is restricted to relatively few neurons in the inner retina and to photoreceptor cells in the outer retina; while presumptive target cells, containing pools of SGC, are widespread and form contiguous fields across the inner and outer nuclear layers (ONL) as well as the ganglion cell layer.

Animals↗
PubMedDate not supplied

Unusual coupling patterns of a cone bipolar cell in the rabbit retina.

In mammals, gap junctions between retinal bipolar cells are generally small and tracer coupling has not been previously demonstrated. In this study, Neurobiotin was injected into the Ba3-type cone bipolar cell, a medium-field cone bipolar cell that ramifies in sublamina a of the rabbit retina. Tracer spread to many other Ba3 bipolar cells, presumably through gap junctions. It also spread to a smaller field bipolar cell called the Ba1 that ramifies at the same depth of the inner plexiform layer. Injection of Neurobiotin into Ba1 bipolar cells did not produce staining beyond the injected cell. Tracer coupling from the Ba3 was therefore both heterologous, in that different cell types were stained, and asymmetric. The unusual properties of this bipolar cell suggest that its function may differ from that of most cone bipolar cells, which are narrow-field, do not overlap, and are poorly coupled to one another.

Animals↗
PubMedDate not supplied

Gap junctions between AII amacrine cells and calbindin-positive bipolar cells in the rabbit retina.

Electrical synapses or gap junctions occur between many retinal neurons. However, in most cases, the gap junctions have not been visualized directly. Instead, their presence has been inferred from tracer spread throughout the network of cells. Thus, tracer coupling is taken as a marker for the presence of gap junctions between coupled cells. AII amacrine cells are critical interneurons in the rod pathway of the mammalian retina. Rod bipolar cell output passes to AII amacrine cells, which in turn make conventional synapses with OFF cone bipolar cells and gap junctions with ON cone bipolar cells. Injections of biotinylated tracers into AII amacrine cells reveals coupling between the AII amacrine cell network and heterologous coupling with a variety of ON cone bipolar cells, including the calbindin-positive cone bipolar cell. To directly visualize gap junctions in this network, we prepared material for electron microscopy that was double labeled with antibodies to calretinin and calbindin to label AII amacrine cells and calbindin-positive cone bipolar cells, respectively. AII amacrine cells were postsynaptic to large vesicle-laden rod bipolar terminals, as previously reported. Gap junctions were identified between AII amacrine cells and calbindin-positive cone bipolar cell terminals identified by the presence of immunostaining and ribbon synapses. This represents direct confirmation of gap junctions between two different yet positively identified cells, which are tracer coupled, and provides additional evidence that tracer coupling with Neurobiotin indicates the presence of gap junctions. These results also definitively establish the presence of gap junctions between AII amacrine cells and calbindin bipolar cells which can therefore carry rod signals to the ON alpha ganglion cell.

Animals↗
PubMedDate not supplied

Treatment of a patient with B cell lymphoma by I-131 LYM-1 monoclonal antibodies.

A patient with Richter's syndrome, a malignant lymphomatous transformation of chronic lymphocytic leukemia, had become moribund with rapidly enlarging masses, granulocytopenia and thrombocytopenia despite the use of conventional chemotherapy and radiotherapy. Greater than ten percent of a test dose of I-131 Lym-1, a murine monoclonal antibody produced against Burkitt's African B cell lymphoma, was accumulated by her tumor. The patient was subsequently treated with a series of injections of I-131 Lym-1 with dramatic clinical response, reduction of tumor volume by x-ray computerized tomography and progression of circulating cellular elements toward normality. Her course over the next ten months was not like that to be expected for Richter's syndrome, which has an average survival of four months. This mode of treatment appears promising.

Aged↗
PubMedDate not supplied

Non-dehalogenation mechanisms for excretion of radioiodine after administration of labeled antibodies.

In patients or mice with cancer the pharmacokinetic behavior of radioiodinated and radiometal chelated antibodies has been observed to be different. Rapid clearance from the tissues and excretion into the urine can occur after injection of radioiodinated antibodies. These observations have been interpreted to reflect in vivo dehalogenation of the antibody. This publication describes a variety of other mechanisms that can underlie these phenomena. These mechanisms include receptor uptake and catabolism of antibody and instability of the labeled antibody due to the labeling conditions. Specifically, the relative masses of chloramine-T and antibody in the iodination reaction mixture, the level of iodination of the antibody, and the amount of antibody administered to the recipient are all factors which can influence the clearance of radioiodinated antibody from the recipient. The final determinant for the different behavior of radioiodinated and In-111 metal chelated antibody relate to the different biologic pathways of indium when compared to iodine.

Animals↗
PubMedDate not supplied

Radioimmunotherapy for breast cancer: treatment of a patient with I-131 L6 chimeric monoclonal antibody.

We report the first treatment of metastatic breast cancer by systemic radioimmunotherapy. The serial therapy doses were chosen based on quantitative imaging data in a treatment planning approach. A terminally ill patient with aggressive, locally advanced breast cancer who had failed radiation treatment and chemotherapy was injected intravenously with radiolabeled I-131 chimeric L6, a human-mouse chimeric lgG1 monoclonal antibody to adenocarcinoma. Initially, an imaging 10 mCi dose of I-131 chimeric L6 (dose 1) deposited 8.8% of the injected dose in her chest wall tumor at 48 hours. Ten days later the patient was given a 150 mCi I-131 chimeric L6 dose (dose 2) followed three weeks later by a 100 mCi dose (dose 3). Tumor uptake and retention were comparable for doses 1 and 2, and decreased for dose 3. Following dose 3 the patient developed a manageable thrombocytopenia and transient Grade IV granulocytopenia. The tumor was observed to decrease in size with peak tumor regression occurring two weeks after dose 3. This partial response (PR) was achieved by radioimmunotherapy at a time when conventional therapy had been unable to impact the growth of the patient's massive and aggressive tumor.

Antibodies, Monoclonal↗
PubMedDate not supplied

Cultural barriers to cancer screening among African American women: a critical review of the qualitative literature.

There have been numerous studies demonstrating the enormous cancer burden for African American women and the impact of structural barriers in the dissemination of cancer control interventions. Few of these studies have dealt with the influence of cultural factors in the success or failure of intervention research. The purpose of this review is to provide a critical appraisal of qualitative studies that inform on social-cultural factors in cancer screening programs for African American women, and to evaluate the extent to which general methodologic criteria have been used in these studies. The article discusses the theoretical underpinnings of social science qualitative methodologies, including ethnography, hermeneutics, ethnomethodology, and symbolic interactionism. Published qualitative studies from 1980 to 1996 on cancer screening among African American women are critically reviewed. Among the themes identified were bruises as contributory to breast cancer development; the low priority women placed on personal preventive screening behaviors in the context of other family health priorities; and the importance of female friends, relatives, and social networks in the flow of cancer information. The importance of qualitative approaches to cancer prevention and control programs and policies is threefold: (a) collection of greater depth of information, (b) identification of processes and relations among behaviors, and (c) framing of variables and hypotheses for quantitative research. Greater emphasis on methodologic rigor will be necessary, however, if qualitative studies of cancer screening are to effectively inform the development of research, programs, and policies.

Black or African American↗