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Biomedical subjects

L L Miller

Publications and source records attributed to L L Miller.

At least 109 records · Page 6Linked to original sources

Bupropion: clinical assay for amphetamine-like abuse potential.

Bupropion hydrochloride (100, 200, and 400 mg), d-amphetamine sulfate (15 and 30 mg), and placebo were compared in 13 volunteers who had histories of amphetamine abuse. Each dose was given orally at intervals of 3 or more days according to a double-blind, randomized crossover design. Bupropion had little or no effect on blood pressure, pulse rate, respiration, body temperature, pupil diameter, subjective appetite, food intake, sleep, or selected subscales of the Addiction Research Center Inventory and Single Dose Questionnaire. Conversely, d-amphetamine was active on most measures. It is concluded that, despite bupropion's reinforcing properties in animals, the compound is not amphetamine-like and is unlikely to give rise to such abuse in humans.

Adult↗

Photoperiod and reproduction in female deer mice.

Female deer mice were exposed to a short day (SD, 6L:18D) photoperiod beginning during 1 of 3 stages of life. In the first experiment, exposure to SD during adulthood resulted in a minimal disruption of reproductive condition; many females bore 2 litters after the onset of this treatment. In the second experiment, females reared on SD from weaning matured normally, as measured by vaginal introitus; however, vaginal closure occurred in approximately one-half of these females by 9 weeks of age. In the third experiment, females were born of mothers housed on either an SD or a long day photoperiod, and were continued on the maternal photoperiod until 6 weeks of postnatal age. The SD photoperiod markedly inhibited reproductive maturation as measured by vaginal patency, ovarian weight, and uterine weight. A comparison of reproductive organ weights and vaginal condition provided evidence for the validity of the latter measure as an index of reproductive state. As assayed by the present testing procedure, the sensitivity of the reproductive system to photoperiod decreases as a function of age in female deer mice.

Animals↗

Reactivity of serum-armed xenogeneic macrophages to breast cancer antigens.

Sera from breast cancer patients contained cytophilic antibody which armed guinea pig peritoneal macrophages. These macrophages then exhibited specific adherence inhibition in the presence of tissue culture tumor antigens. These antigens were obtained from primary cultures of autologous or allogeneic breast cancer cells. Sera from control subjects for the most part did not induce macrophage adherence inhibition in the presence of these same antigens.

Animals↗

Synthesis of factor II antigen by isolated perfused rat liver.

Rat Factor II (prothrombin), isolated and purified by chromatography on Blue Dextran-agarose, was used to raise an antiserum in rabbits. On the basis of single radial immunodiffusion measurements. Factor II synthesis by isolated perfused rat liver amounted to 0.54 mg/300 cm2 body surface area of the liver donor in 10 h. Corresponding measurements of Factor II coagulant activity revealed cumulative synthesis of 802 Iowa units. Coumadin added to the liver perfusate blocked production of Factor II coagulant activity, but did not change synthesis of the immunologically measured protein. In perfusions in which either heparin or citrate was used as anticoagulant, synthesis of albumin was not affected by the choice of anticoagulant but bile production and synthesis of Factor II were significantly less in citrate perfusions.

Animals↗

Relationship between plasma delta-9-tetrahydrocannabinol concentration and pharmacologic effects in man.

The relationship between each of two pharmacologic effects (tachycardia and psychological "high") of delta-9-tetrahydrocannabinol (THC) and plasma THC concentration was investigated in three male and three female experienced marihuana smokers. Each subject smoked 1% THC cigarette on two occasions separated by 2 h. Heart rate and subjective psychological self-rating were determined frequently throughout the 4 h study period. Data were analyzed by calculating the area under the parameter versus time curves, constructing hysteresis plots, and calculating the decay rate constants from pharmacologic effect versus time plots. In both males and females, dose inhaled and psychological response were apparently equivalent for the first and second cigarettes. While all subjects exhibited marked tachycardia in response to the first cigarette, heart rate in both male and female subjects was not increased as markedly during the second cigarette. Interestingly, female subjects had less tachycardiac response than males during the second cigarette. Hysteresis plots revealed that both heart rate and subjective psychological effect were elicited in an effect compartment which was "deep" relative to the reference plasma compartment. The time courses of tachycardiac and psychological responses lagged behind the plasma THC concentration-time profile. Zero-order decay rate constants for subjective psychological rating did not change substantially from the first to second cigarette. This study suggest that plasma THC concentration is a poor predictor of simultaneously occurring physiological and psychological pharmacologic effects.

Adult↗

Net biosynthesis of antithrombin III by the isolated rat liver perfused for 12--24 hours. Compared with rat fibrinogen and alpha-2 (acute-phase) globulin, antithrombin III is not an acute phase protein.

Antithrombin III-heparin cofactor has been isolated from normal rat plasma, purified to homogeneity on acrylamide gel electrophoresis and used to prepare a monospecific antiserum in rabbits. Measurements of rat antithrombin III were made by a single radial immunodiffusion assay. Net synthesis of antithrombin III was investigated during 12- or 24-h perfusions of the isolated rat liver. In perfusions performed under basal conditions cumulative synthesis of antithrombin-III was observed to occur at a rate sufficient to replace the total circulating plasma antithrombin III in about 6 h. In perfusions performed under full supplementation conditions which greatly enhanced synthesis of fibrinogen and alpha-2 (acute-phase) globulin (known acute-phase reactant proteins) net synthesis of antithrombin III was not significantly greater than that observed in control perfusions. Although these prolonged perfusion studies conclusively demonstrate net synthesis of antithrombin III by the isolated rat liver, they afford no evidence that this protein is an acute-phase reactant.

Animals↗

Levels of processing and acute effects of marijuana on memory.

Subjects' memory for lists of words was tested following the smoking of a single marijuana cigarette containing 1.4% delta 9-THC or a placebo cigarette. During list presentation, each word was preceded by an orienting question which required one of four types of linguistic information (orthographic, phonetic, semantic, or syntactic). Free recall tests were administered immediately after each list (IFR) and following IFR for all five lists (FFR). Results indicated that subjects recalled fewer words while intoxicated with marijuana. There was no interaction between drug condition and level of processing in IFR, but a complex relationship mediated by time was seen in FFR. Drug subjects were more likely to forget meaningfully processed words on recently presented lists. The data provided little support for the hypothesis that marijuana differentially affects the processing and retention of different types of linguistic information.

Adult↗

Marijuana: dose effects on pulse rate, subjective estimates of intoxication, free recall and recognition memory.

The effect of marijuana on memory as measured by free recall and recognition, pulse rate and self ratings of intoxication was evaluated in 16 male volunteers. Marijuana containing 0, 5, 10 or 15 mg delta9-THC was administered to all subjects by smoking in 4 sessions separated by a 1 week interval. Free recall was reduced in a dose related manner by the drug, but recognition memory was unaffected. A 2 sec word presentation rate produced inferior recall in comparison to a 4 sec rate, but this variable did not interact with drug condition. Intrusion errors increased following intoxication but this effect was not systematically related to dosage of delta9-THC. Both pulse rate and self ratings of intoxication increased with dosage.

Adult↗

Marijuana: effects on free recall and subjective organization of pictures and words.

The free recall of pictures and words was compared following the administration of marijuana or placebo in a multitrial free recall task. Since pictures are thought to be registered in both visual and verbal memory stores with this encoding being mediated by some form of mental imagery, it was predicted that marijuana would produce a greater deficit in word recall in comparison to picture recall because the drug has been reported to facilitate imagery. A trend in the opposite direction followed intoxication; picture recall was inferior to word recall in the later stages of acquisition. Although overall recall was inferior under marijuana, no differences were found between the treatment conditions in subjective organization as determined by a variety of clustering measures. Recall performance following marijuana intoxication was positively related to level of recall performance in the placebo condition.

Adult↗

Marijuana: effects on storage and retrieval of prose material.

In a two phase design, an attempt was made to differentiate the effect of marijuana on the storage and retrieval of prose material. In the first phase, 40 male subjects were administered a single 500 mg marijuana cigarette containing 2.1%delta9-THC or a placebo cigarette. Fifteen minutes after smoking, they listened to and at the same time read a narrative passage of approximately 200 words in length. Subsequently, an immediate free recall test was given in which subjects were required to write down as much of the story as they could remember. The second phase was conducted 24h later. Marijuana and placebo subjects were randomly subdivided into four groups with half of the subjects participating in the same drug condition as occurred on day one while the others switched drug state. Fifteen minutes after smoking, all subjects recalled the passage presented on day one and then were given 24 questions concerning facts and events in the story which could be answered in a few words. These questions served as retrieval cues. Following this, a new passage was presented in the same manner as occurred on day one. After an immediate free recall test, another cued recall test was administered. Results indicated that marijuana reduced immediate recall under both cued and uncued conditions incomparison to placebo. No relative cued recall advantage was found in the marijuana groups for the old or new story and marijuana produced only a moderate decrement in recall of the old story on day two. However, marijuana given in the second phase significantly reduced memory for items recalled in the initial phase irrespective of drug or cueing condition in phase one, suggesting that retrieval was also affected. Some decrement in recall of the new story did occur as a function of drug state change in group M-P. This effect was related to the serial position of input items. Serial position did not interact with drug state under any other recall condition.

Cannabis↗

Critical adjustment of cysteine and glutamine concentrations for improved clonal growth of WI-38 cells.

Clonal growth of WI-38 cells with a plating efficiency of 45% has been achieved in a synthetic nutrient mixture (MCDB 102) supplemented with either whole or dialyzed fetal bovine serum precisely. Deviation by a factor of three in either direction from the optimum concentration (9.0 x 10(-5) M) eliminates essentially all clonal growth. A high concentration of glutamine (2.5 x 10(-3) M) is also needed for optimum clonal growth.

Blood↗

Marijuana and memory impairment: effect on free recall and recognition memory.

The effect of marijuana on memory was evaluated by presenting two groups of 17 male volunteers with lists of repeated or nonrepeated words following administration of a single marijuana cigarette containing 14 mg delta9-THC. An immediate free recall, final free recall and recognition memory test followed. Results indicated that marijuana significantly decreased immediate and final free recall but only slightly influenced recognition memory. Rate of acquisition on the repeated lists was the same for both groups. Long term retention of encoded information was not influenced by marijuana. The shape of the serial position curves departed slightly from those reported by other investigators in that some effects of the drug on the recency portion of the curve were noted. Both internal and external intrusions were elevated under marijuana.

Adult↗