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Biomedical subjects

S L Mills

Publications and source records attributed to S L Mills.

At least 37 records · Page 2Linked to original sources

Trends in cigarette smoking among US adolescents, 1974 through 1991.

OBJECTIVES: The purpose of this study was to determine national trends in adolescent cigarette smoking prevalence. METHODS: We conducted trend analyses based on 1974 through 1991 current smoking prevalence data among persons aged 12 through 19 years from the National Household Surveys on Drug Abuse, High School Seniors Surveys, and National Health Interview Surveys. RESULTS: Overall smoking prevalence declined much more rapidly from 1974 through 1980 (1.9 percentage points annually among younger adolescents; the range among surveys of older adolescents was 0.2 to 2.0 percentage points annually) than from 1985 through 1991 (0 to 0.5 percentage points annually among all adolescents). Since 1980, smoking has generally declined at a slightly faster rate among older female adolescents than among male adolescents. Smoking among Black adolescents of all ages declined in nearly every survey population during each study period (range among surveys: 1974-1985 = 1.0 to 2.9 percentage points; 1985-1991 = 0.7 to 1.5 percentage points annually); for White adolescents, only minimal declines in smoking have occurred since 1985. CONCLUSIONS: Since 1974, major changes in adolescent smoking patterns have occurred, especially among Blacks. The overall slowing rate of decline in smoking prevalence since 1985 may indicate success of increased tobacco advertising and promotional activities targeted at adolescents or inadequate antitobacco education efforts.

Adolescent↗

An energy model of interframe interval effects in single-step apparent motion.

A computational model was developed to explain the effects of an interframe interval (IFI) in single-step apparent motion experiments. In these experiments a stimulus appears in one position, disappears, and then reappears in a shifted position after a short or long IFI. If the luminance during the IFI matches the mean luminance of the stimulus frames, long IFIs result in perceived motion opposite the short-IFI conditions. Brighter or darker IFIs, however, do not support the reversed motion effect. The model possess the following defining characteristics: (1) a biphasic ("transient") channel whose signalled direction of motion reverses with changes of IFI duration; (2) a combined direction-opponent output which is the sum of directional responses developed in two channels--biphasic ("transient") and monophasic ("sustained"); (3) a signal/noise weighting of the contributions of the two channels to the final directional output of the system. Predictions of the model about the effects of IFI intensity and viewing eccentricity were tested and confirmed in two new psychophysical experiments. The interpretations of past studies which included a role for second-order motion mechanisms in explaining IFI duration effects were reexamined. Further empirical tests of the model were outlined.

Humans↗

The United States National Cancer Institute and the science of tobacco control research.

U.S. efforts to control tobacco use and tobacco-related morbidity and mortality have been reasonably successful over the past 3 decades, during which there has been a 34% reduction in adult smoking. Nevertheless, tobacco use remains a significant public health problem in the U.S., with more than 430,000 tobacco-related deaths per year and over one fourth of the population continuing to smoke. Many organizations are involved in tobacco-use control activities, the most broadly focused of which is that of the National Cancer Institute (NCI). The NCI's program is described and its emphasis on a data-based decision matrix in its approach to tobacco and cancer control research and applications of research is discussed. Finally, future approaches to tobacco-use control in the U.S. are suggested.

Forecasting↗

All indoleamine-accumulating cells in the rabbit retina contain GABA.

The indoleamine-accumulating amacrine cells of the rabbit retina are wide-field and numerous. They form a dense plexus in sublamina 5 of the inner plexiform layer where they make reciprocal synapses with rod bipolar cells. To provide a quantitative test for the colocalization of serotonin (5-HT) and gamma-aminobutyric acid (GABA) in the rabbit retina, we designed two parallel double-label experiments. In the first series, the indoleamine-accumulating cells were labeled with 5,7-dihydroxytryptamine (5,7-DHT), which was subsequently visualized by photooxidation in the presence of diaminobenzidine. This was combined with autoradiography for 3H-muscimol. In the second and complementary series, 3H-5-HT uptake was combined with postembedding GABA immunocytochemistry. These two experiments provided essentially identical results: over 98% of the indoleamine-accumulating amacrine cells were double-labeled. This means that, within the limit of experimental error, all the indoleamine-accumulating amacrine cells are GABAergic. The indoleamine-accumulating amacrine cells account for 15-20% of a large diverse group of GABA amacrine cells. In addition, the rare type 3 indoleamine-accumulating cells and fine processes running in the optic fiber layer were double-labeled. If there is insufficient 5-HT to support a transmitter role in the rabbit retina, our results suggest that the indoleamine-accumulating cells may use GABA as a neurotransmitter. Thus, rod bipolar cells, in common with other bipolar cell types, receive extensive negative feedback at GABA-mediated reciprocal synapses.

5,7-Dihydroxytryptamine↗

Morphology of bipolar cells labeled by DAPI in the rabbit retina.

The morphology, distribution, and coverage of certain cone bipolar cell types were investigated in rabbit retina. Brief in vitro incubation of isolated rabbit retina in the fluorescent dye 4,6-diamino-2-phenylindole labeled only a few cell types in the inner nuclear layer. Intracellular injection of Lucifer Yellow into these types showed them to be horizontal cells and cone bipolar cells. All stained bipolar cells ramified in sublamina a of the inner plexiform layer (IPL) and formed three classes. Two types ranged from 20 to 60 microns in diameter in both plexiform layers; the other large bipolar cell was 40-70 microns in diameter in the outer plexiform layer (OPL) and up to 150 microns in diameter in the IPL. The brightest type was narrowly stratified in the outer portion of sublamina a. Its density increased from about 500 cells/mm2 in the periphery to about 2,500 cells/mm2 in the visual streak. Staining of neighboring cells of this type showed that processes in the IPL rarely crossed, but often converged at a common site so as to impart a "honeycomb" appearance to a single sublayer of retina. The other small bipolar cell was similar in density and coverage, but stratified diffusely throughout sublamina a. The large bipolar cell stratified narrowly in the distal portion of sublamina a and was more sparsely distributed. Whether determined by staining adjacent cells or by density vs. area calculations, coverage in the OPL approached 1 for each type, as did coverage in the IPL for the two types with narrow fields.

Animals↗

Labeling and distribution of AII amacrine cells in the rabbit retina.

The fluorescent dye 4,6-diamino-2-phenylindole (DAPI) has previously been used to label starburst amacrine cells selectively in the rabbit retina and AII amacrine cells in the cat retina. Using the rabbit retina, we show that intraocular injection of DAPI labels starburst amacrine cells as seen 1-2 days later. In contrast, after a brief in vitro incubation with DAPI, AII amacrine cells are selectively labeled. Amacrine cells were identified by intracellular staining with Lucifer Yellow. AII amacrine cells are arranged in a regular mosaic with a density of 2,800 cells/mm2 near the visual streak declining to about 500 cells/mm2 in the far periphery. The coverage of the lobular dendritic field in sublamina alpha is approximately 1.5 across the retina, but the coverage of the fine dendritic field in sublamina b increases from 3 centrally to 4 in the inferior periphery, and to above 8 in the superior periphery.

Animals↗

Color vision following intense green light exposure: data and a model.

Hue discrimination, spectral sensitivity, and mathematical models of both are presented for a rhesus monkey which was exposed to intense green light. One of the monkey's eyes was blue-blinded in a previous experimental procedure and the other was color normal. The results of green light exposure showed a loss of sensitivity on both measures, with greater loss in the blue-blinded eye. Although there was considerable loss of hue-discrimination in the blue-green spectral regions, hue-discrimination at the point of best discrimination, 590 nm, remained unaffected. This pattern of results poses difficulties for models of hue discrimination, and has resulted in the proposed model employing three opponent color channels. The number of free-parameters are minimized and the integration between spectral sensitivity and hue discrimination enhanced by deriving parameters used in modeling hue discrimination from spectral sensitivity or vice versa.

Animals↗

Quantitative imaging of mouse L-6 monoclonal antibody in breast cancer patients to develop a therapeutic strategy.

L-6, a mouse IgG2a anti-adenocarcinoma monoclonal antibody (MoAb) with favorable immunopathology and mouse biokinetics, was evaluated for cancer radioimmunotherapy by pharmacokinetic studies in 10 patients with breast cancer. The effect of escalating the preinfused protein dose was studied in two patients at each level, using 50, 100, 150, 200 and 400 mg of unlabeled L-6 prior to a 10 mCi imaging dose of 131I L-6. Quantitative imaging, and blood and urine clearances were obtained. After the 50 mg preinfusion, rapid blood clearance and lung extraction of the radiopharmaceutical occurred immediately post injection. Greater preload amounts of L-6 were associated with an increase in the intercept of the slow phase of the blood clearance from 17 to 22% injected dose (ID) with 50 mg to 70 to 80% ID with 400 mg (P less than 0.01). Lung uptake of the radiopharmaceutical immediately post injection decreased from 15 to 19% ID (50 mg) to 6 to 8% ID (400 mg). Tumors were visualized only after larger L-6 preloads, but in these patients small chest tumors contained 0.6-1.2% ID (0.1% ID/g maximum). This study suggests that L-6 reactive sites that are readily available in the lung can be saturated, so that a subsequent dose of I-131 L-6 is delivered to the tumor. This approach provides a new strategy for developing an effective method for radioimmunotherapy using a MoAb that has some cross-reactivity. Quantitative imaging contributed to detection of the cross-reactivity and the strategy for overcoming it.

Adenocarcinoma↗

Cholinergic amacrine cells in the rabbit retina accumulate muscimol.

The cholinergic amacrine cells of the rabbit retina form two mosaics placed symmetrically on either side of the inner plexiform layer. Recently, these cells have been reported to contain immunocytochemical markers for GABA. In this paper, we labeled the cholinergic cells with DAPI, then incubated the retina in [3H]-muscimol, a neuronal marker for GABA. Subsequently, we converted the DAPI fluorescence of the displaced cholinergic matrix to an opaque product by photooxidation in the presence of DAB. Autoradiography showed that all of the displaced cholinergic amacrine cells were labeled with [3H]-muscimol, thus confirming the immunocytochemical results. The cholinergic cells account for approximately 80% of the cells in the ganglion cell layer which take up [3H]-muscimol.

Acetylcholine↗

Quitting smoking in the United States in 1986.

In an analysis of recent behavior with regard to quitting smoking, detailed histories were obtained on a representative sample of 5,623 Americans who had smoked in the year preceding the 1986 Adult Use of Tobacco Survey. An estimated 55.8 million Americans smoked regularly for some period during the year prior to the survey. Approximately one third (34.8%) quit for at least a day during the year prior to the survey, 28.3% quit for at least 7 days during the year prior to the survey, and 16.2% were still not smoking at the time of the survey. Of those who quit for a day, 54% had relapsed by the time of the survey. Demographic characteristics, such as age, sex, race, marital status, and education, were evaluated as predictors of making a major attempt to quit for 7 days or more. Among those who had made a major attempt, a similar analysis was done predicting success in maintaining cessation for 3 months or more. Ordinal logistic regression analyses showed that younger age and higher education predicted a major attempt to quit. There was only one group who differed markedly from all others: those who were younger and were more highly educated. Older age and being white predicted those who abstained for 3 months or longer.

Adolescent↗

In vitro studies with the platelet-reactive antibody 50H.19 and its fragments.

The platelet-reactive monoclonal antibody 50H.19, its F(ab')2 fragments, and 99m-technetium (99m-Tc)-labeled fragments used in thrombus imaging were evaluated for their ability to cause platelet aggregation. The intact antibody caused a dose-dependent platelet aggregation in either platelet-rich plasma (PRP) or defined buffer solutions. The F(ab')2 fragments did not cause platelet aggregation except at high calcium concentrations. Neither stannous-ion-treated antibody fragments nor 99m-Tc-labeled antibody fragments caused platelet aggregation. The antibody-induced platelet aggregation was completely inhibited by 8-bromo-cAMP, caffeine, theophylline diltiazem, and staurosporin; partially inhibited by EDTA, EGTA, cytochalasin B, colchicine, aspirin, or indomethacin. Treatment of platelets with the intact 50H.19 antibody resulted in phosphorylation of a 40K dalton platelet protein, similar to that caused by treatment with phorbol myristate acetate (PMA). Phosphorylization of the 40K protein was not observed after treatment with either the 50H.19 F(ab')2 fragments or the calcium ionophore A23187.

Antibodies, Monoclonal↗

Fractionated radioimmunotherapy of B-cell malignancies with 131I-Lym-1.

Eighteen patients with Stage 4 B-cell malignancies, which were primarily of intermediate or high grade and progressive despite multiple drug chemotherapy and external irradiation, were treated with fractionated doses of 131I-labeled Lym-1. Lym-1 is an IgG2a monoclonal antibody that was produced by immunizing mice with Raji cell nuclei that originated from a patient with African Burkitt's lymphoma. Despite advanced disease, 10 of the patients had objective evidence for a complete or partial remission. Toxicity was very modest except in one patient who developed hypotension. Dose-dependent hepatic uptake of Lym-1 was observed in the patients and in BALB/c mice suggesting receptor-mediated recognition of this murine antibody.

Antibodies, Anti-Idiotypic↗

Trends in smoking by age and sex, United States, 1974-1987: the implications for disease impact.

Using data from the 1974-1987 National Health Interview Surveys, we report trends in current smoking prevalence and quit ratios (the proportion of those who have ever smoked who no longer smoke) for men and women in the age groups 20-24, 25-44, 45-64, and 65 years and older. Current smoking prevalence decreased linearly for men in all age subgroups except 65 and older and for women ages 25-44 and 45-64 years only. The quit ratios increased linearly within each age/sex subgroup except for men and women ages 20-24 years. Overall, there were about 1.4 million fewer male smokers and over 1 million more female smokers in 1987 than there were in 1974. Between 1974 and 1987, the population ages 25-44 years increased by approximately 47%, and the population 65 years and older increased by approximately 34%. As a result, between 1974 and 1987, the actual number of smokers increased among men ages 25-44 years (8% increase), women ages 25-44 years (15% increase), and women ages 65 years and older (50% increase). These data suggest that even with favorable recent changes in the overall smoking prevalence of the U.S. population, the disease impact of smoking will increase for decades, especially among women. This scenario will be mitigated if increased attention is given to cessation among women in general and to the post-World War II generation of both male and female smokers.

Adult↗

Red/green opponency in the rhesus macaque ERG spectral sensitivity is reduced by bicuculline.

Spectral-sensitivity curves were derived from the a-, b-, and d-waves of rhesus monkey ERGs after injection of bicuculline, strychnine, or no drug. Without drug injection, the a- and d-wave curves were well-fit by an additive model of weighted photoreceptor absorption spectra, while the b-wave curve requires inhibitory terms to produce an adequate fit. Bicuculline, but not strychnine, reduced the weight assigned to the inhibitory terms in a dose-dependent fashion, to the point that no inhibition was evident. The results suggest that GABAergic synapses are required for the expression of red/green color opponency in primate bipolar cells.

Animals↗

Treatment of B cell malignancies with 131I Lym-1 monoclonal antibodies.

Lym-I is a murine IgG2a monoclonal antibody (MAb) that is B-cell specific but has greater avidity for malignant B cells when compared with normal B lymphocytes. It was originally produced by immunizing mice with nuclei of cultured cells from a patient with Burkitt's lymphoma. Ten patients with progressive refractory B-cell malignancies were treated with 131I-labelled Lym-I. Treatment with 131I Lym-I produced complete or partial remissions in 4 patients. Toxicity did not occur or was mild in most patients. The only significant complications included two instances of fistula secondary to necrotic lymphoma and one instance of hypotension. Human antimouse antibodies occurred in only 2 patients after multiple injections of Lym-I antibody. This experience was in contrast to treatment of B-cell malignancies with unconjugated Lym-I alone. Unconjugated Lym-I also caused no significant toxicity but was less effective than 131I Lym-I.

Antibodies, Monoclonal↗