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J S Miller

Publications and source records attributed to J S Miller.

At least 145 records · Page 8Linked to original sources
PubMed1990

Comparison of vancomycin- and teicoplanin-induced histamine release and "red man syndrome".

Twelve healthy adult males participated in a double-blind, randomized, two-way crossover study to determine histamine release and the frequency and severity of "red man syndrome" (RMS) following intravenous administration of vancomycin (15 mg/kg of body weight over 60 min) and teicoplanin (15 mg/kg over 30 min). Concentrations of vancomycin and teicoplanin in serum and concentrations of histamine in plasma were measured at baseline and during and after each infusion. Erythema and pruritus were classified a priori as mild, moderate, or severe. The extent of erythema was determined by the use of a burn chart, and pruritus was assessed by the subject with a rank scale. Global severity of RMS was determined by summation of the individual scores for pruritus and erythema. Baseline areas under the concentration-time curve for histamine were not significantly different for the vancomycin and teicoplanin treatments. Vancomycin caused RMS in 11 of 12 subjects (9 severe and 2 moderate cases) and was associated with a significant increase in plasma histamine (46.7 +/- 31.3 ng.min/ml, P less than 0.05). In contrast, teicoplanin did not cause RMS or elicit significant histamine release (8.7 +/- 13.2 ng.min/ml). Peak concentrations of vancomycin and teicoplanin in serum were 58.8 +/- 8.4 and 148.0 +/- 31.8 micrograms/ml, respectively (P less than 0.05). Assuming equal efficacy, these data suggest that teicoplanin may be a safe alternative agent in subjects experiencing severe RMS due to vancomycin; however, further studies in the clinical setting are needed.

Adult↗
PubMed1990

Cloning and characterization of a second complementary DNA for human tryptase.

A second cDNA for human tryptase, called beta-tryptase, was cloned from a mast cell cDNA library in lambda ZAP. Its nucleotide sequence and corresponding amino acid sequence were determined and compared with those of a previously cloned tryptase cDNA, now called alpha-tryptase. The 1,142-base sequence of beta-tryptase encodes a 30-amino acid leader sequence of 3,089 D and a 245-amino acid catalytic region of 27,458 D. The amino acid sequence of beta-tryptase is 90% identical with that of alpha-tryptase, the first 20 amino acids of the catalytic portions being 100% identical. This identity, together with recognition of each recombinant protein by monoclonal antibodies directed against purified tryptase validate the tryptase identity of both alpha-tryptase and beta-tryptase cDNA molecules. Modest differences between the nucleic acid sequences of alpha- and beta-tryptase occurred throughout the cDNA molecules except in the 3' noncoding regions, which were identical. Although most highly conserved regions of amino acid sequence in the trypsin superfamily are conserved in both tryptase molecules, beta-tryptase has one carbohydrate binding site compared to two in alpha-tryptase, and one additional amino acid in the catalytic sequence. Regions of the substrate binding pocket in beta-tryptase (DSCQ, residues 218-221; SWG, residues 243-245) differ slightly from those in alpha-tryptase (DSCK, residues 217-220; SWD, residues 242-244). The presence of both alpha- and beta-tryptase sequences in each haploid genome was indicated by finding alpha- and beta-tryptase specific fragments after amplification by PCR of genomic DNA in 10 unrelated individuals. Localization of both alpha- and beta-tryptase sequences to human chromosome 16 was then performed by analysis of DNA preparations from 25 human/hamster somatic hybrids by PCR. It is now possible to assess the expression of each tryptase cDNA by mast cells and the relationship of each gene product to the active enzyme.

Amino Acid Sequence↗
PubMed1990

Current management of choledocholithiasis.

Choledocholithiasis may be managed by surgical extraction of stones or endoscopic papillotomy with extraction of stones. To evaluate these methods of management, the charts of all patients with choledocholithiasis admitted to Crawford Long Hospital of Emory University between April 1, 1983, and April 30, 1988, were reviewed. One hundred patients were identified; 42 were treated by common bile duct exploration (CBDE) and 58 had endoscopic papillotomy with extraction of stones (EP) as their initial treatment. The two groups were similar in regards to age, but the CBDE group had more comorbid conditions (average 2.5/patient in CBDE vs 1.8/patient in EP) and a higher incidence of acute cholecystitis and/or cholangitis (74% of CBDE patients; 24% of EP patients). Successful extraction of all stones occurred in 79 per cent of CBDE patients and 90 per cent of EP patients. Of those patients with retained stones following CBDE, all were later extracted by EP. Of patients having EP as their initial procedure, 24 per cent required repeat endoscopic procedures for extraction of residual stones and only six patients (10.4%) required CBDE for retained stones. Morbidity was lower (10% vs 23%) and hospital stay shorter (3.6 days vs 10.4 days) in the EP than CBDE patients; thus, the two groups are not completely comparable. Mortality was similar in the two groups (1.7% EP, 2.3% CBDE).

Adolescent↗
PubMed1989

Pathophysiology of transitional tumor cell adherence to sites of urothelial injury in rats: mechanisms mediating intravesical recurrence due to implantation.

The mechanism by which transitional tumor cells adhere to areas of urothelial injury and the means by which heparin prevents this phenomenon were studied. Scanning electron microscopy and a radiolabeled tumor cell adherence assay were used to assess the activity of heparin and a "nonglycosaminoglycan" thrombolytic agent, recombinant tissue plasminogen activator, in preventing tumor cell adherence to areas of urothelial injury. Systemically administered heparin and intravesical therapy with recombinant tissue plasminogen activator duplicated the activity of intravesical heparin. Scanning electron microscopy showed tumor cells entrapped at the injury surface in a RBC/fibrin clot, which was prevented by intravesical heparin. These data suggest that clotting cascade activation by urothelial injury is the mechanism by which particulate adherence to the urothelium occurs. Interruption of this process by local or systemic anticoagulation with heparin or shifting of the equilibrium of clot formation/lysis toward thrombolysis with recombinant tissue plasminogen activator prevents tumor cell adherence. Intravesical thrombolytic therapy may represent a new approach to recurrence prophylaxis for superficial bladder carcinoma.

Animals↗
PubMed1989

Ontogenetic differences in short-term retention of Pavlovian conditioning.

In the present series of studies 16- and 21-day-old rats acquired an aversion to a black compartment (CS+) paired with footshock, only if given preconditioning exposure to a white chamber (CS-) not paired with footshock. The strength of conditioning was inversely related to the length of the retention interval in both age groups. However, the rate of forgetting was accelerated in the 16-day-old subjects, indicating infantile amnesia for the conditioned aversion. Strength of conditioning was also inversely related to the length of the CS-/CS+ interval in both age groups, indicating that expression of the aversion is critically dependent on an active memory of the CS- at the time of conditioning. Additionally, there was an ontogenetic decrease in the rate of forgetting of the CS-, indicating infantile amnesia for elements of the conditioning episode that did not predict occurrence of US.

Aging↗
PubMed1989

Human mast cell proteases and mast cell heterogeneity.

Mast cell neutral proteases are distinctive markers of the MC(T) and MC(TC) cells in humans. Measurements of tryptase levels in vivo serve as an overall indicator of mast cell activity. Further research is needed to evaluate the functional role of these proteases as well as each mast cell type in situations related to both health and disease.

Biomarkers↗
PubMed1989

Age-dependent facilitation of taste-footshock conditioning by prior exposure to the training context.

Among adult rats, gustatory stimuli are easily associated with illness, but not with external unconditioned stimuli such as footshock. Recent evidence indicates, however, that this cue-to-consequence specificity may vary ontongenetically. The present studies examined the acquisition of an aversion to a taste paired with footshock in 5- and 15-day-old rats. Consistent with previous reports, 5-day-old rats avoided the taste that preceded footshock, while 15-day-old subjects did not express an aversion to the taste paired with footshock. Exposure to the training context for either 1 or 5 h prior to conditioning disrupted taste-footshock conditioning in the 5-day-old subjects. For the 15-day-old subjects, 1 h of pre-conditioning exposure to the training context had no effect on conditioning, whereas a longer duration of preexposure promoted conditioning to the taste cue. The results suggest ontogenetic differences in stimulus selection.

Aging↗
PubMed1989

Facilitation of acquisition and retention in preweanling but not postweanling rats by the presence of familiar home-nest material.

A series of four experiments examined the effect of the presence of stimuli from the home nest on the acquisition and retention of aversively motivated behaviors in preweanling and adult rats. In Experiment 1, training in the presence of home-nest shavings facilitated acquisition of a T-maze discrimination to escape footshock for 16-day-old rats but not for adults. Experiment 2 demonstrated that the extent to which preweanlings were familiar with the home shavings determines the degree to which these stimuli facilitate spatial discrimination learning. When clean shavings were made more familiar than soiled home-nest stimuli (by changing the shavings every day) clean shavings enhanced discrimination performance, whereas no enhancement of learning by home shavings was observed. Experiment 3 extended the generality of the enhancement effect to a conditioned location aversion and examined the extent to which this facilitative effect was due to the tendency for home-nest shavings to elicit approach responses. Expression of the conditioned aversion was enhanced in subjects conditioned in the presence of home shavings, regardless of whether the home shavings were presented with the CS+, the CS-, or both. Experiment 4 determined that the enhanced expression of learning in the context of home-nest stimuli observed for preweanlings did not occur among subjects trained shortly after weaning. Collectively, these data suggest that whereas the enhancement of learning and retention by familiar home-nest stimuli enjoys generality across a number of conditioning situations, the effect may be limited to a relatively brief period during ontogeny.

Aging↗
PubMed1989

Cloning and characterization of complementary DNA for human tryptase.

The amino acid sequence of human mast cell tryptase was determined from corresponding cDNA cloned from a lambda ZAP library made with mRNA derived from a human mast cell preparation. Tryptase is the major neutral protease present in human mast cells and serves as a specific marker of mast cells by immunohistologic techniques and as a specific indicator of mast cell activation when detected in biologic fluids. Based on nucleic acid sequence, human tryptase consists of a 244-amino acid catalytic portion of 27,423 D with two putative N-linked carbohydrate binding sites and a 30-amino acid leader sequence of 3,048 D. A His74, Asp120, Ser223 catalytic triad and four cystine groups were identified by analogy to other serine proteases. Regions of amino acid sequence that are highly conserved in serine proteases, in general, were conserved in tryptase. The catalytic portion of human tryptase had an 84% amino acid sequence similarity with that of dog tryptase; their leader sequences had a 67% similarity. Asp217 in the substrate binding pocket of human tryptase is consistent with a specificity for Arg and Lys residues at the site of cleavage (P1), whereas Glu245 is consistent with the known preference of human tryptase for substrates with Arg or Lys also at P3, analogous residues also being present in dog tryptase. Asp244, which is substituted for the Gly found in dog tryptase and in most serine proteases, is present in the putative substrate binding pocket and may confer additional substrate specificity on human tryptase for basic residues. Further studies now can be designed to elucidate these structure-function relationships.

Amino Acid Sequence↗
PubMed1989

Age-related differences in short-term retention of separable elements of an odor aversion.

The rate of forgetting over short intervals was tested in preweanling rats, 8, 12, or 18 days postnatal, using procedures that may have analytical advantages over other tests of short-term retention. Separate tests of retention were conducted for the simple occurrence of an odor and for the occurrence of an odor paired with a mild footshock. Forgetting of odors with either of two histories, incidental or target, was more rapid the younger the preweanling, over intervals of less than an hour. There was some indication of more rapid forgetting for incidental than target odors. Finally, although exposure to a CS- (an odor not paired with footshock) was necessary for conditioning of the CS+ (an odor paired with footshock) in rats 8 or 12 days of age, exposure to a CS- had no influence on conditioning of the CS+ in preweanlings 18 days of age. The age-related differences in forgetting over intervals less than an hour long suggest that substantial age-related differences in forgetting can occur that, it is likely, are not accounted for by differential growth.

Aging↗
PubMed1988

Effects of temperature elevation on mRNA and protein synthesis in Leishmania mexicana amazonensis.

The transition from the promastigote stage to the amastigote stage in Leishmania appears to involve a sequence of steps which enable the parasite to adapt to its new environment. In this study, transformation from the promastigote to an amastigote-like stage was induced by temperature elevation and the effects on protein synthesis and the mRNA population were analyzed. Whereas significant changes in the polypeptide complement of the cell were observed, few, if any, changes were seen at the level of the mRNAs as determined by translation in a cell-free system. Increasing the growth temperature caused a rapid cessation of beta-tubulin synthesis but the abundance and sizes of mRNAs specific for beta-tubulin were unaltered. These data suggest that the regulation of beta-tubulin under these conditions is occurring at the level of translation.

Animals↗
PubMed1988

Use of recombinant retroviruses to study the regulation of integrated adenovirus early promoters.

Adenovirus E1A gene products are capable of modulating the expression of a variety of integrated genes. To study the mechanisms by which this regulation occurs, recombinant retroviruses have been utilized to establish cell lines containing an integrated copy of either the adenovirus E2 or E3 promoter adjacent to the bacterial guanine phosphoribosyl transferase (GPT) gene. These cell lines have been characterized with respect to both basal and E1A-induced levels of GPT gene expression. Cell lines with low levels of GPT gene expression showed increased expression in the presence of E1A, whereas cell lines with high basal levels of GPT gene expression had decreased GPT RNA levels in the presence of E1A. Further characterization of these cell lines revealed E1A modulation of the accumulation of RNA initiating at a retrovirus promoter adjacent to the E2 or E3 promoter. The use of the GPT gene as a marker of E2 or E3 promoter activity has allowed the isolation of cell lines which have spontaneously increased their levels of GPT RNA. A preliminary characterization of four of these cell lines has indicated that GPT gene expression is increased as a result of cis activation of the E2 promoter.

Adenovirus Early Proteins↗
PubMed1988

Ligand-modulated regulation of progesterone receptor messenger ribonucleic acid and protein in human breast cancer cell lines.

We have examined the effects of estrogen and progestin agonist and antagonist ligands on regulation of progesterone receptor (PR) protein and mRNA levels in a variety of human breast cancer cell lines. By Northern blot analysis, using human PR cDNA probes, PR mRNA in T47D and MCF-7 cells appears as five species of approximately 11.4, 5.8, 5.3, 3.5, and 2.8 kilobases. PR mRNA species are not detected in the PR protein-negative breast cancer cell lines MDA-MB-231 and LY2. T47D cells contain high levels of PR mRNA and protein (detected by hormone binding assay or Western blot analysis), and the PR protein and mRNA content of T47D cells are reduced to about 10% of the control level within 48 h of treatment with 10 nM promegestone; 17, 21-dimethyl-19-nor-pregna-4,9-diene-3, 20-dione (R5020) or 16 alpha-ethyl-21-hydroxy-19-nor-pregn-4-ene-3,20-dione (ORG2058), both potent progestins. In contrast, treatment of T47D cells with the antiprogestin 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]-17 alpha-(1-propynyl)-estra- 4, 9-dien-3-one) (RU38486) reduces PR protein and mRNA levels only transiently. PR protein and mRNA are virtually undetectable in control MCF-7 cells grown in the absence of estrogens. When estradiol is administered to MCF-7 cells, the PR mRNA and protein levels increase gradually and proportionately (10- or 40-fold, respectively, in 3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1987

Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis.

Better methods are needed to assess mast-cell activation in vivo and to distinguish the activation of mast cells from that of basophils. Tryptase, a neutral protease selectively concentrated in the secretory granules of human mast cells (but not basophils), is released by mast cells together with histamine and serves as a marker of mast-cell activation. In 17 patients with systemic mastocytosis, concentrations of tryptase in plasma were linearly related to those of histamine (P less than 0.01). Eleven of the 17 patients had tryptase levels of 4 to 88 ng per milliliter, indicating ongoing mast-cell activation. In each of six patients who experienced corresponding anaphylactic reactions after penicillin, aspirin, or melon ingestion, a wasp sting, exercise, or antilymphocyte globulin injection, tryptase levels in serum ranged from 9 to 75 ng per milliliter, indicating mast-cell activation during each of these events. In contrast, serum tryptase levels were less than 5 ng per milliliter in all patients presenting with myocardial disease (n = 8, 6 with hypotension) or sepsis (n = 6, 3 with hypotension) and in the controls (n = 20). One patient had a myocardial infarction after anaphylaxis in response to a wasp sting and an elevated tryptase level of 25 ng per milliliter. Thus, the plasma or serum tryptase level is a diagnostic correlate of mast-cell-related events.

Anaphylaxis↗
PubMed1986

Repeated testing attenuates conditioned place preference with cocaine.

Cocaine-treated rats acquired a preference for cocaine-associated contextual stimuli (CS) relative to saline-injected control rats. However, when animals were given repeated tests for conditioned place preference intermittent between conditioning trials, they displayed an attenuation in strength of conditioning. This attenuation was not due to pharmacologic tolerance (Experiment 1), but rather reflected a disruption in learning due to exposure to the CS alone (Experiment 2). Like other examples of classical conditioning, the strength of the conditioned response (CR) as assessed by the conditioned place preference model may be influenced by partial reinforcement.

Animals↗