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Biomedical subjects

D Byrd

Publications and source records attributed to D Byrd.

At least 37 records · Page 2Linked to original sources
PubMed1997

3H-morphine-6beta-glucuronide binding in brain membranes and an MOR-1-transfected cell line.

Morphine-6beta-glucuronide (M6G) is a potent morphine metabolite. In an effort to further explore its mechanisms of action, we synthesized 3H-M6G of high specific activity and examined its binding. Although its affinity toward traditional mu receptors is similar to morphine in binding assays in brain and in Chinese hamster ovary cells stably transfected with MOR-1, M6G is >100-fold more potent than morphine in analgesic assays. This apparent discrepancy cannot be explained by differing intrinsic activities of the two drugs because both agents are partial agonists with similar efficacies in adenylyl cyclase assays in the transfected cell lines. Behavioral studies have implied the possibility of a distinct M6G receptor. Detailed binding studies in brain tissue reveal evidence for heterogeneity. Nonlinear regression analysis of 3H-M6G saturation studies reveals two components. The lower-affinity component (K(D) = 1.93 +/- 0.6 nM) corresponds to labeling of traditional mu receptors. In addition, 3H-M6G labels another site of low abundance with very high affinity (K(D) = 68 +/- 7 pM). Competition studies indicate that both sites are relatively mu selective. However, several compounds clearly distinguish between the two sites. These binding studies support the concept of a unique M6G receptor responsible for its analgesic activity.

Animals↗
PubMed1996

Auditory selective attention: an fMRI investigation.

In the present experiment, 25 adult subjects discriminated speech tokens ([ba]/[da]) or made pitch judgments on tone stimuli (rising/falling) under both binaural and dichotic listening conditions. We observed that when listeners performed tasks under the dichotic conditions, during which greater demands are made on auditory selective attention, activation within the posterior (parietal) attention system and at primary processing sites in the superior temporal and inferior frontal regions was increased. The cingulate gyrus within the anterior attention system was not influenced by this manipulation. Hemispheric differences between speech and nonspeech tasks were also observed, both at Broca's Area within the inferior frontal gyrus and in the middle temporal gyrus.

Adult↗
PubMed1995

Features and outcome of no-reflow after percutaneous coronary intervention.

No-reflow is an uncommon complication that may occur after revascularization of patients with acute myocardial infarction, after interventions in saphenous vein bypass grafts, and after the use of some new interventional devices. However, the clinical impact of no-reflow after coronary intervention is unknown. Accordingly, this study examined the incidence, clinical presentation, angiographic characteristics, and outcome of no-reflow after percutaneous coronary intervention. No-reflow was defined as an acute reduction in antegrade flow (< or = 1, as defined by the Thrombolysis in Myocardial Infarction [TIMI] trial) not attributable to abrupt closure, high-grade stenosis, or spasm of the original target lesion. Among 10,676 coronary interventions performed between October 1988 and June 1993, no-reflow occurred in 66 patients (0.6%). These patients were compared with a subgroup of 500 consecutive patients who did not exhibit no-reflow. The incidence of no-reflow was 30 of 9,431 (0.3%) for percutaneous transluminal coronary angioplasty, 1 of 317 (0.3%) for excimer laser, 8 of 104 (7.7%) for Rotablator (Heart Technologies, Bellevue, Washington), 21 of 469 (4.5%) for extraction atherectomy, and 6 of 355 (1.7%) for directional atherectomy. Compared with those without no-reflow, patients with no-reflow experienced a 10-fold higher incidence of in-hospital death (15%) and acute myocardial infarction (31%). Correlates of in-hospital mortality included acute myocardial infarction on presentation (p = 0.006) and final flow < 3 (as defined by the TIMI trial) at completion of the procedure (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Integral membrane proteins associated with the nuclear lamina are novel autoimmune antigens of the nuclear envelope.

We have analyzed sera from 55 patients, most with rheumatic diseases, that all react with the nuclear envelope of human cells in immunofluorescence microscopy. The molecular targets of these autoantibodies were characterized by immunoblot analysis of fractions derived from rat liver nuclear envelopes. While numerous sera were found to react with previously characterized autoimmune antigens of the nuclear envelope including nuclear lamins and the pore complex glycoprotein gp210, a substantial number of the sera were found to recognize relatively minor integral membrane proteins of the nuclear envelope associated with the nuclear lamina (LAP 1A and LAP 2), which have not been previously identified as autoantigens. Autoantibodies to LAP 1A and LAP 2 are present in 9 and 29% of the patient sera, respectively. Only autoantibodies to lamins A/C were encountered more frequently (in 31% of the sera) than autoantibodies to LAP 2, suggesting that LAP 2 may be among one of the most prominent autoantigens of the nuclear envelope in rheumatic disease patients. Since recent studies have suggested that LAP 1A and LAP 2 may be involved in attaching lamins and chromosomes to the nuclear envelope, these findings could promoted understanding of nuclear envelope functions as well as autoimmunity.

Autoantibodies↗
PubMed1995

Urinary calcium and oxalate excretion in children.

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1-7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean +/- SD = 0.39 +/- 0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34 +/- 0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61-280) mumol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6-82) mumol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28-49) vs. 22 (range 16-29) and 23 (range 22-27) mumol/mol respectively, P < 0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18 +/- 0.05 vs. 1.06 +/- 0.03, P < 0.03 and 0.84 +/- 0.03, P < 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Using regions and indices in EPG data reduction.

This note describes how dynamic electropalatography (EPG) can be used for the acquisition and analysis of articulatory data. Various data reduction procedures developed to analyze the electropalatographic data are reported. Specifically, these procedures concern two interesting areas in EPG data analysis--first, the novel use of speaker-specific articulatory regions and second, the development of arithmetic indices to quantify time-varying articulatory behavior and reflect reduction and coarticulation.

Electric Stimulation↗
PubMed1995

Command hallucinations in outpatients with schizophrenia.

BACKGROUND: The presence of command hallucinations in individuals with schizophrenia may result in an increase in clinical monitoring to reduce the perceived risk of violent behavior. However, the issue of whether command hallucinations hold any clinical relevance in relatively stable outpatient samples has not been established. METHOD: The clinical and research records of individuals with schizophrenia who participated in outpatient research protocols at the University of California, San Diego were reviewed for the presence of command hallucinations. Information on clinical characteristics was collected in a detailed chart review from 106 patient records. RESULTS: Command hallucinations were reported by one half of all patients with auditory hallucinations, and these hallucinations often were violent in content. Yet, in over a third of the patients, these hallucinations had not been documented in their clinical charts, but instead were uncovered during a secondary source review. Patients with command hallucinations generally did not differ on prognostic or clinical course variables. However, the 2 patients who committed suicide during the study were patients with command hallucinations. CONCLUSION: Although command hallucinations may be more frequent than clinicians generally note, in most cases they have minimal influence on the outcome of schizophrenia. However, in outpatients with schizophrenia who have a history of suicide attempts, suicidal command hallucinations should be taken seriously.

Adult↗
PubMed1994

Halotolerance of Methanobacterium thermoautotrophicum delta H and Marburg.

Methanobacterium thermoautotrophicum delta H and Marburg were adapted to grow in medium containing up to 0.65 M NaCl. From 0.01 to 0.5 M NaCl, there was a lag before cell growth which increased with increasing external NaCl. The effect of NaCl on methane production was not significant once the cells began to grow. Intracellular solutes were monitored by nuclear magnetic resonance (NMR) spectroscopy as a function of osmotic stress. In the delta H strain, the major intracellular small organic solutes, cyclic-2,3-diphosphoglycerate and glutamate, increased at most twofold between 0.01 and 0.4 M NaCl and decreased when the external NaCl was 0.5 M. M. thermoautotrophicum Marburg similarly showed a decrease in solute (cyclic-2,3-diphosphoglycerate, 1,3,4,6-tetracarboxyhexane, and L-alpha-glutamate) concentrations for cells grown in medium containing > 0.5 M NaCl. At 0.65 M NaCl, a new organic solute, which was visible in only trace amounts at the lower NaCl concentrations, became the dominant solute. Intracellular potassium in the delta H strain, detected by atomic absorption and 39K NMR, was roughly constant between 0.01 and 0.4 M and then decreased as the external NaCl increased further. The high intracellular K+ was balanced by the negative charges of the organic osmolytes. At the higher external salt concentrations, it is suggested that Na+ and possibly Cl- ions are internalized to provide osmotic balance. A striking difference of strain Marburg from strain delta H was that yeast extract facilitated growth in high-NaCl-containing medium. The yeast extract supplied only trace NMR-detectable solutes (e.g., betaine) but had a large effect on endogenous glutamate levels, which were significantly decreased. Exogenous choline and glycine, instead of yeast extract, also aided growth in NaCl-containing media. Both solutes were internalized with the choline converted to betaine; the contribution to osmotic balance of these species was 20 to 25% of the total small-molecule pool. These results indicate that M. thermoautotrophicum shows little changes in its internal solutes over a wide range of external NaCl. Furthermore, they illustrate the considerable differences in physiology in the delta H and Marburg strains of this organism.

2,3-Diphosphoglycerate↗
PubMed1992

Expression of elongation factor-1 gamma-related sequence in human pancreatic cancer.

A cDNA clone designated pPDC-1 was isolated from a cDNA library prepared against poly(A+)RNA isolated from the human pancreatic adenocarcinoma cell line, Capan-2. The cDNA corresponds to a 1.7-kilobase mRNA that is expressed at higher levels in seven of nine pancreatic tumors than in their corresponding normal tissues. It is also expressed in normal human kidney, intestine, pancreas, stomach, placenta, lung, brain, spleen, and liver. A computer search of the Intelligenetics System of all available nucleotide sequences revealed a 60% homology between the nucleotide sequence of the pPDC-1 cDNA and that of elongation factor-1 gamma from Artemia. The deduced amino acid sequence shared 53% identity with the amino acid sequence for the Artemia elongation factor-1 gamma.

Aged↗
PubMed1992

Preliminary results on speaker-dependent variation in the TIMIT database.

A set of phonetic studies based on analysis of the TIMIT speech database is presented. Using a database methodological approach, these studies detail new results in speaker-dependent variation due to sex and dialect region of the talker including effects on stop release frequency, speaking rate, vowel reduction, flapping, and the use of glottal stop. TIMIT was found to be fertile ground for gathering acoustic-phonetic knowledge having relevance to the phonetic classification and recognition goals for which TIMIT was designed, as well as to the linguist attempting to describe regularity and variability in the pronunciation of read English speech.

Databases, Factual↗
PubMed1985

Central nervous system toxicity and cerebrospinal fluid pharmacokinetics of intraventricularly administered bleomycin in beagles.

The neurotoxic effects and cerebrospinal fluid (CSF) pharmacokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg/week. Doses higher than 0.3 mg/week produced marked elevation of CSF protein levels and a necrotizing vasculitis within the central nervous system. Pharmacokinetic studies were performed approximately 1 month after the completion of the toxicity studies. [3H]inulin was used as a reference compound. Both [3H]inulin and bleomycin were cleared from the CSF more slowly than in previous studies and more slowly than in normal dogs, which suggests that bulk CSF absorption was reduced by the drug, probably secondary to protein-induced blockage of the arachnoid granulations through which CSF is normally absorbed. Because a "minimally toxic" dose of bleomycin (approximately 0.1 mg/week) produces a CSF C X t of only 1.9 mg/min/ml, we believe that a Phase I clinical trial would be too dangerous given the limited therapeutic potential that a dose of 0.1 mg/week could achieve.

Animals↗
PubMed1985

Central nervous system toxicity and cerebrospinal fluid pharmacokinetics of intraventricular 3-[(4-amino-2-methyl-5-pyrimidinyl)ethyl]-1-(2-chloroethyl)-1-nitro soureas and other nitrosoureas in beagles.

The central nervous system toxicity and cerebrospinal fluid (CSF) pharmacokinetics of 3-[(4-amino-2-methyl-5-pyrimidinyl)ethyl]-1-(2-chloroethyl)-1- nitrosoureas, a (ACNU) were determined in beagles and compared to those for three other nitrosoureas, 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, and chlorozotocin. Of the four drugs, ACNU was tolerated best and at doses of 0.2 to 0.8 mg/week for 8 consecutive weeks. We found that the average half-time for CSF elimination of ACNU was 18 min (range, 12 to 38 min). This value exceeded the known rate of ACNU decomposition in aqueous solution (28 to 29 min), implying that the disappearance of ACNU from CSF was due to hydrolytic decomposition and cellular entry and/or transcapillary loss across central nervous system capillaries. The drug exposure integral (C X t) of ACNU in the CSF after a "toxic dose low" of 0.8 mg in the dogs would achieve the equivalent of in vitro cell kills in excess of 3 logs for rat 9L and human glioma 126 cells. As a potential therapeutic agent for meningeal neoplasia, the major limiting factor may be that the CSF elimination of ACNU is rapid compared to its equilibration time from ventricle to spinal- and cerebral convexity-subarachnoid space. Based on these results, we have instituted clinical Phase I trials of intra-CSF ACNU.

Animals↗
PubMed1984

CNS toxicity and CSF pharmacokinetics of intraventricular DFMO and MGBG in beagle dogs.

We have developed a beagle dog model to study the pharmacology and toxicology of anticancer drugs administered through the 3rd or lateral ventricles. A Foltz-type reservoir was implanted SC and connected by tube into a cerebral ventricle. Drugs were administered directly into the reservoir; CSF sampling of drugs administered into the ventricle was achieved directly by tapping the reservoir or by percutaneous puncture of the cisterna magna. In the current study, we evaluated the CSF pharmacokinetics and CNS toxicity of two inhibitors of polyamine metabolism, alpha-difluoromethylornitine (DFMO) and methylglyoxal bisguanylhydrazone (MGBG). Both drugs were judged too toxic to justify intrathecal or intraventricular studies with these agents in patients.

Animals↗
PubMed1980

[Excretion of transamination products in hyperphenylalaninemia (author's transl)].

A low-phenylalanine diet was given for a period of three weeks to four untreated adult phenylketonurics with mental deficiency. One week before the diet was started, in the course of the diet and one week after its termination, some transamination products of phenylalanine, tryptophan and histidine were determined quantitatively. Each of the transamination products showed a positive correlation to the serum phenylalanine levels of the patients, probably due to the large affinity of 4-hydroxyphenylpyruvic acid and phenylpyruvic acid for the amino groups of the aromatic amino acids. This may also explain the low levels of epinephrine, norepinephrine and serotonine which has been observed by other authors in untreated phenylketonurics. Accordingly, treated phenylketonurics should suffer from a chronic deficiency of biogenic amines after termination of the low-phenylalanine diet.

Adult↗