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Biomedical subjects

L L Miller

Publications and source records attributed to L L Miller.

At least 91 records · Page 5Linked to original sources
PubMed1988

The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene.

Ferritin is a ubiquitous and highly conserved protein which plays a major role in iron homeostasis. We have identified and sequenced a full-length cDNA for murine ferritin heavy chain. The isolated cDNA is 819 nucleotides in length. It includes 546 nucleotides which encode a protein of 182 amino acids, a 5' noncoding sequence of 120 nucleotides, and a 3'-noncoding region of 153 nucleotides. The sequence displays a high degree of homology to human ferritin H, and includes a portion of the iron-responsive element conserved in chick, frog, and human ferritin. Tumor necrosis factor (TNF), a cytokine which mediates elements of the stress response, induces expression of ferritin H mRNA. Both mouse TA1 adipocytes and human muscle cells increase expression of ferritin H mRNA 4-6-fold after 48 h exposure to TNF. This increase occurs both prior and subsequent to differentiation of adipocytes and muscle cells, and is accompanied by an increase in the synthesis of the ferritin H subunit. These findings suggest a novel role for TNF in iron metabolism.

Adipose Tissue↗
PubMed1988

A randomized, double-blind, placebo-controlled trial of transfer factor as adjuvant therapy for malignant melanoma.

One hundred and sixty-eight evaluable patients participated in a randomized, double-blind study of transfer factor (TF) versus placebo as surgical adjuvant therapy of Stage I and Stage II malignant melanoma. Eighty-five patients received TF prepared from the leukocytes of healthy volunteer donors; eighty-three participants received placebo. Therapy was initiated within 90 days of resection of all evident tumor and continued until 2 years of disease-free survival or the occurrence of unresectable dissemination of melanoma. Known prognostic variables were similarly distributed in the treatment and control groups, documenting the randomization efficacy. Three endpoints were analyzed: disease-free interval, time to Stage III metastasis, and survival. After a median follow-up period of 24.75 months, there was a trend in favor of the placebo group with regard to all three endpoints and this was significant (P less than or equal to 0.05) for time to Stage III metastasis. These findings indicate that TF is not effective as surgical adjuvant therapy of malignant melanoma.

Clinical Trials as Topic↗
PubMed1988

Persistent grossly elevated plasma immunoglobulin A levels in untreated streptozocin-induced diabetic rats.

Experimental diabetes mellitus was induced in adult male and female rats by injecting streptozocin (STZ; 60 mg/kg i.p.) in preparation for a screening survey of changes in the pattern of undenatured plasma proteins, as revealed by two-dimensional (2-D) gel electrophoresis followed by silver staining. As early as 8-12 days later, the 2-D gels revealed three high-molecular-weight plasma protein spots, which persisted for 150 days in the blood of untreated diabetic rats. Such spots were not seen in plasma of normal control rats. Evidence is presented for the presumptive characterization of these proteins as oligomers of immunoglobulin A (IgA). Specific measurement of total IgA content of diabetic plasma samples by single-radial immunodiffusion, after reduction with dithiothreitol and alkylation with iodoacetamide, reveals that IgA content increases linearly from control values of 11.1 +/- 4.6 to 358 +/- 249 mg/dl (means +/- SE) 21 days after STZ and persists at these high levels for as long as 150 days. Diabetic rats injected daily with insulin showed IgA levels only two to four times higher than normal. Neither experiments designed to quantitate the rates of clearance (catabolism plus excretion) of 125I-labeled secretory IgA from the circulation of normal and diabetic rats nor measurement of total IgA in the bile from diabetic and normal bile fistula rats supports the view that slowed clearance from the circulation or impaired biliary excretion in the diabetic rat causes observed gross hyperimmunoglobulinemia A.

Animals↗
PubMed1988

Increased plasma IgA, sIgA, and C3- and IgA-containing immune complexes with renal glomerular deposits in diabetic rats.

Male Sprague-Dawley rats were fasted 18 h and given streptozocin (STZ; 60 mg/kg body wt i.p.). The resultant diabetes mellitus, not treated with insulin, was associated with persistent manifoldly increased plasma IgA levels, as measured by single-radial immunodiffusion after reduction with dithiothreitol and alkylation with iodoacetamide. Also observed were concurrent increases in plasma levels of secretory IgA (sIgA) and of C3- and IgA-containing immune complexes (C3-IgA-CIC). After 104 days without insulin treatment, six of the diabetic rats were given daily injections of 2 U of insulin for 11 days. Insulin treatment was associated with a precipitous decrease in plasma levels of IgA, sIgA, and C3-IgA-CIC. Cessation of insulin treatment resulted in restoration of greatly increased levels of all three IgA-containing species. Histoimmunofluorescence studies of kidneys from untreated rats with diabetes of 192-324 days revealed glomerular capillary wall and mesangial deposits reacting strongly with anti-IgA (alpha-chain-specific) antiserum. Kidneys from two of the diabetic rats (324 days) were tested with anti-rat C3 and anti-rat secretory component (SC) antisera, and they reacted positively. Control kidneys from normal rats examined simultaneously were negative. The concurrent changes in plasma levels of three IgA-containing species in the untreated STZ-induced diabetic rat and the demonstration of abnormal immunoreactive IgA-containing renal glomerular deposits make this experiment an attractive model for studying the possible role of disturbed IgA metabolism in the pathogenesis of diabetic nephropathy.

Animals↗
PubMed1987

Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin.

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.

Adult↗
PubMed1985

Reproductive development in male deer mice exposed to aggressive behavior.

Male deer mice (Peromyscus maniculatus bairdii) were reared in a long photoperiod and housed individually from 3 weeks of age until they were killed 2, 4, or 6 weeks later. Males that were exposed to aggressive females for 2 min, three times per week, were of normal body weight and healthy, but had smaller reproductive organs than did males exposed to a control treatment. Reproductive development in male deer mice is responsive to at least two classes of social stimuli: pheromones and aggressive behavior.

Aggression↗
PubMed1985

Behavioral perturbations in the vitamin K-deficient rat.

Anecdotal observations of the behavior of rats with a vitamin K-deficiency suggested that this deficiency was associated with hypoactivity, general malaise, and a lack of exploratory behavior. These observations were pursued by assessing locomotor activity in a circular photocell-monitored track, open-field activity, and radial-arm maze performance in rats rendered vitamin K-deficient by dietary depletion or by warfarin treatment. There was a significant reduction (approximately 25% at the median) in the locomotor activity of dietary vitamin K-deficient rats compared with rats fed a control diet. In the open-field, warfarin administration was associated with a significant shift from more exploratory behaviors to less exploratory behaviors. Consistent with these findings, radial-arm maze assessment showed a comparative reduction in locomotor activity in the dietary vitamin K-deficient rats with no alteration in performance, i.e., short-term memory. These animal behavioral studies suggest that sub-clinical and clinical vitamin K-deficiency may contribute to physical and psychiatric symptomatology.

Animals↗
PubMed1984

A double-blind study of bupropion and placebo in depression.

Bupropion HCl, a new nontricyclic antidepressant, produced marked improvement in 49 hospitalized patients with primary depression at doses of 300-600 mg/day. Bupropion resulted in statistically significant differences from placebo as early as day 5, and by the end of the 4-week study 79% (N = 27) of the bupropion patients and 13% (N = 2) of the placebo patients showed much to very much improvement. Bupropion and placebo had similar side effect profiles. Tremor and sweating were reported more often with bupropion and headache, nausea, and tiredness with placebo.

Adult↗
PubMed1984

Photosensitive stages in pubertal development of male deer mice (Peromyscus maniculatus).

Male deer mice (Peromyscus maniculatus bairdii) were exposed to a long (15L:9D) or short (6L:18D) photoperiod during four stages of development. At 6 weeks of postnatal age degree of pubertal development was determined by measurement of testis and seminal vesicle weights and area of the androgen-dependent sebaceous gland. Continuous exposure to a short photoperiod beginning before conception (i.e. mother kept in short days), at conception, or at birth markedly retarded pubertal development. Initiation of short-day treatment after weaning at 3 weeks of age was partly effective in inhibiting puberty. Males exposed to long days beginning at weaning were stimulated fully, however, having reproductive organs as large at 6 weeks of age as those of males housed on long days for the entire experiment. These results indicate that pubertal development in male deer mice is regulated by early postnatal, but not prenatal, photoperiod. However, early after weaning, males are more responsive to increasing than to decreasing photoperiod.

Animals↗
PubMed1983

Relationships between several pharmacokinetic parameters and psychometric indices of subjective effects of delta 9-tetrahydrocannabinol in man.

This study explored the relationships in man between various pharmacological effect of delta 9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective "high" rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, "high"). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective "high" rating, rather than other ratings more specific for particular moods.

Dronabinol↗
PubMed1983

Bupropion, d-amphetamine, and amitriptyline-induced conditioned taste aversion in rats: dose effects.

Nine groups of rats (n = 6 per group) were adapted to a daily one-half hour period of water availability. When intake had stabilized, they were allowed access to a 0.1% (w/v) solution of saccharin, and immediately afterward were given IP injections of isotonic saline; bupropion HCl (10.0, 20.0, or 40.0 mg/kg); d-amphetamine-sulfate (0.5, 1.0, 2.0 mg/kg); or amitriptyline HCl (5.0, 10.0, or 20.0 mg/kg) in a volume of 1 ml. The lowest dose of each compound as chosen to be equipotent in screening tests used to identify potential antidepressants. Following 2 days of access to water alone, all groups were given a choice between water and saccharin for 3 consecutive days. All compounds induced taste aversions in a dose-related manner, but amitriptyline induced greater and longer-lasting aversions than either bupropion or d-amphetamine which were equipotent over the dose range studied. As such, this is the first demonstration that bupropion and amitriptyline, two clinically effective antidepressants, can induce taste aversions and replicates as well the common finding that d-amphetamine has substantial taste aversion-inducing properties. The ability of these compounds to induce taste aversions could be mediated through their effects on central catecholaminergic processes although amitriptyline has significant peripheral anticholinergic effects.

Amitriptyline↗
PubMed1983

Effects of bupropion on body weight.

Patients' weights were assessed during placebo-controlled, amitriptyline-controlled, and uncontrolled bupropion trials. Low-moderate (50-450 mg/day) to moderate-high (300-750 mg/day) doses of bupropion were consistently associated with a lack of weight gain (average weight loss of 1-2 pounds); placebo was associated with an average weight gain of 1 lb and 75-225 mg/day of amitriptyline was associated with an increase of 3-9 lb. Bupropion treatment was rarely accompanied by reports of appetite change and had no statistically significant effect on caloric intake when compared to placebo.

Amitriptyline↗
PubMed1983

Overview of clinically significant adverse reactions to bupropion.

During the clinical development of bupropion (Wellbutrin) 1,153 depressed patients and 157 normal volunteers received bupropion (doses, 15-1200 mg/day); 177 placebo-treated and 196 tricyclic-treated patients (doses, 25-300 mg/day) also participated in these trials to provide a control comparison. Safety measures during the clinical trial program included adverse event symptomatology, vital signs, clinical laboratory examinations, and EEGs. There were no bupropion-related changes in vital signs, clinical laboratory, or EEG results severe enough to warrant treatment discontinuation. The most common cause for discontinuation in the bupropion (9.1%), placebo (6.8%), and tricyclic groups (9.2%) was agitation/excitement. The only adverse experience considered of medical significance in bupropion patients was major motor seizure. The incidence of a seizure was less than 1 per 1,000 at usual outpatient doses and less than 1 per 100 at usual inpatient doses. These incidences appear to be comparable to those seen with equally therapeutic doses of tricyclic antidepressants.

Adult↗