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Biomedical subjects

C E Wright

Publications and source records attributed to C E Wright.

At least 73 records · Page 4Linked to original sources
PubMed1996

Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance of T and B cell targets, historic sera and autologous controls.

There is limited information regarding the role of flow cytometry crossmatching (FCXM) in primary cadaver kidney allografting and even less about B cell reactivity and graft survival (GS). Furthermore, there is little or no published data concerning reaction strength (cutoff value), the effect of historic sera reactions, and the usefulness of performing autologous crossmatches (XMs) on GS. These factors were examined retrospectively on 214 primary transplants performed from August 1991 to January 1994 with follow-up to July 1995. Three-color FCXMs were done on a 1024-channel BD-FACScan, and the shift in median channel fluorescence (MCF) over the negative control was calculated. All patients had a negative T cell (AHG) and warm B cell (2 was, extended incubation) cytotoxicity XM, and none was excluded in calculating GS. A quantitative effect was noted as stronger MCF shifts vs. T or B cells correlated with decreased GS (r = 0.98 and 0.92, respectively). Significant differences were seen with cutoff values of T = 50 and B = 110 which were 1.7-1.8 times the SD above the mean MCF of normal sera controls T neg patients (n = 198) and 1- and 3-yr actuarial GS of 86% and 79% compared to T pos patients (n = 16) of 75% and 49%, p = 0.008. B neg patients (n = 177) had 1- and 3-yr GS od 86% and 81% compared to B pos patients (n = 37) of 78% and 47%, p = 0.005. Most informative was the analysis of combined T and B cell FCXM results. Three years GS for T neg - B neg patients (n = 171) was 81% and for T pos - B neg patients (n = 6), it was 83%, p = 0.98. The 27 T neg - B pos group's GS was lower at 62% but did reach significance. Poorest GS was seen for T pos - B pos patients (n = 10) at 23%, p = 0.0001. Reaction patterns showed that T cells detected only HLA Class I antibodies, whereas B cells detected both Class I and II. Historic sera (> or = 1 month old) reactivity influenced GS. Patients with > or = 2 past sera positive but current serum negative reactions vs. T or T plus B cells (n = 7) had a poor 29% GS, while those historically positive only vs. B cells (n = 7) had 100% GS. On the other hand, patients positive only with the current serum (n = 16) had 2-yr GS of 100% (false positive test?), while patients whose current and historic sera reactions were positive (n = 21) had a 25-50% GS (true positive test?). About 1 in 15 patients (19%) displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift values from those vs. the donor converted 17 patients to the T neg - B neg or T pos - B neg group whose 2-yr actual GS was not significantly different (p > 0.8) from those initially testing T neg B neg vs. their donors.

Actuarial Analysis↗
PubMed1995

An outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection associated with nebulized albuterol therapy.

OBJECTIVE: To investigate an outbreak of Burkholderia (formerly Pseudomonas) cepacia respiratory tract colonization and infection in mechanically ventilated patients. DESIGN: A retrospective case-control and bacteriologic study. SETTING: Veterans Affairs medical center. PATIENTS: 42 mechanically ventilated patients who developed respiratory tract colonization or infection with B. cepacia and 135 ventilator-dependent controls who were not colonized and did not develop infections. MEASUREMENTS: Clinical and demographic data; benzalkonium chloride concentrations and pH levels in albuterol sulfate solutions; repetitive-element polymerase chain reaction (PCR)-mediated molecular fingerprinting on eight patient isolates and three environmental B. cepacia isolates that were available for study. RESULTS: 42 patients had B. cepacia respiratory tract colonization or infection. Observation of intensive care unit and respiratory care personnel showed faulty infection control procedures (for example, the same multiple-dose bottle of albuterol was used for many mechanically ventilated patients). More case patients (39 [92.9%]) than controls (95 [70.4%]; P = 0.006) received nebulized albuterol, and case patients (67.5 treatments) received more treatments than controls (18 treatments; P < 0.001). In-use albuterol solutions had pH values that were unstable, and benzalkonium chloride concentrations declined over time to levels capable of supporting bacterial growth. Medication nebulizers and in-use bottles of albuterol harbored B. cepacia. Molecular fingerprints of patient isolates and environmental B. cepacia isolates were identical using repetitive-element PCR. No further isolates of B. cepacia were identified after institution of appropriate infection control procedures. CONCLUSIONS: Multiple-dose medications and reliance on benzalkonium chloride as a medication preservative provide a mechanism for nosocomial spread of microorganisms, particularly if infection control procedures are not carefully followed. Repetitive-element PCR is a useful fingerprinting technique for molecular epidemiologic studies of B. cepacia.

Aged↗
PubMed1995

Crystallisation of alpha-crustacyanin, the lobster carapace astaxanthin-protein: results from EURECA.

Crystallisation of alpha-crustacyanin, the lobster carapace astaxanthin-protein was attempted under microgravity conditions in EURECA satellite using liquid-liquid diffusion with polyethyleneglycol (PEG) as precipitant; in a second reaction chamber phenol and dioxan were used as additives to prevent composite crystal growth. Crystals of alpha-crustacyanin grown under microgravity from PEG were larger than those grown terrestrially in the same apparatus under otherwise identical conditions. On retrieval, the crystals from PEG were shown to be composite and gave a powder diffraction pattern. The second reaction chamber showed leakage on retrieval and had also been subjected to rapid temperature variation during flight. Crystal fragments were nevertheless recovered but showed a powder diffraction pattern. It is concluded, certainly for liquid-liquid diffusion using PEG alone, that, for crustacyanin, although microgravity conditions resulted in an increase in dimensions of crystals, a measurable improvement in molecular ordering was not achieved.

Animals↗
PubMed1995

Temporal rescaling of sample and complex rations in rhythmic tapping.

Two well-established phenomena in temporal performance--preference for simple ratios over complex ratios and the ability to proportionately rescale temporal patterns--were examined together. Unlike the case with simple ratios, participants (3 trained musicians) showed only a limited ability to learn complex ratios and no ability to proportionately rescale them. These differences suggest that different mechanisms are used to produce the 2 ratio types. Systematic biases observed in the performances of the simple ratios (6 trained musicians) were modeled by assuming that an additive timing component, which is unequal for short and long intervals and changes with base rate, overlays a system that preferentially produces simple ratios. The general pattern of results was consistent with the view that rhythmic learning builds on or modifies a system of innate preferences.

Adult↗
PubMed1995

Molecular epidemiology of infections due to Enterobacter aerogenes: identification of hospital outbreak-associated strains by molecular techniques.

Molecular techniques were used to study the epidemiology of infections due to Enterobacter aerogenes in a tertiary-care hospital. Sixty-two clinical isolates were collected from 43 patients over 3 months. Restriction endonuclease analysis (REA) of chromosomal DNA and repetitive-element polymerase chain reaction (rep-PCR) with primers based on repetitive extragenic palindromic (REP) and enterobacterial repetitive intergenic consensus (ERIC) bacterial DNA sequences were used for genomic fingerprinting. REA with HindIII or EcoRI yielded complex banding patterns that differentiated community-acquired from some hospital-acquired organisms. Less complex fingerprints were obtained with rep-PCR, which also distinguished between epidemiologically unrelated strains. More discriminatory DNA fingerprints were provided by rep-PCR when REP primers rather than ERIC primers were used. Two clusters of genomically distinct isolates from patients with recent or current exposure to the hospital environment were identified by REA and rep-PCR. Most isolates within each cluster contained characteristic plasmids, and some isolates contained additional plasmids. These results suggest colonization and infection with genotypically related strains of E. aerogenes in a nosocomial setting. Although REA and plasmid profiling are useful techniques for the epidemiological typing of E. aerogenes, genomic fingerprinting with rep-PCR may offer the advantages of ease, speed, and broad species applicability over existing molecular-typing techniques.

Adult↗
PubMed1995

Hemodynamic and autonomic reflex effects of chronic N-type Ca2+ channel blockade with omega-conotoxin GVIA in conscious normotensive and hypertensive rabbits.

The effects of chronic administration of omega-conotoxin GVIA (omega-CTX), an N-type Ca2+ channel blocker, on hemodynamics and autonomic reflexes were studied in conscious normotensive (sham) and hypertensive (wrap) New Zealand white rabbits. During surgery, a pulsed Doppler-flow probe was implanted around the lower abdominal aorta, and both kidneys were wrapped in cellophane (wrap) or left undisturbed (sham). Rabbits were studied 4 weeks later on 5 consecutive days. On days 1-4, hemodynamics, the baroreceptor-heart-rate (HR) reflex induced by drugs and the Bezold-Jarisch-like reflex evoked by serotonin, were measured before and 2 h after administration of omega-CTX (10 micrograms/kg i.v. bolus). On day 5, hemodynamics and reflexes were again assessed, but no further omega-CTX was given. On day 1, omega-CTX caused falls in mean arterial pressure (MAP) of 17 +/- 3 and 27 +/- 5 mm Hg in sham (n = 6) and wrap (n = 11) rabbits, respectively, with tachycardia. Hindquarter vascular conductance (HVC) increased > 35% in both groups. On days 2-4, omega-CTX still caused falls in MAP; however it was progressively less than on day 1. HR and HVC did not change. After omega-CTX on day 1, there was marked attenuation of the sympathetic components and decrease in the vagal components of the baroreceptor-HR reflex curves, with HR range decreasing by > 61% in sham and wrap rabbits. These curves remained similar over the next 4 days, and were unaffected by further omega-CTX. However, omega-CTX had no effect on the vagally mediated Bezold-Jarisch-like reflex. In auxiliary experiments in vitro, omega-CTX (1 nM) inhibited sympathetic, but not vagal, responses to electrical nerve stimulation of rabbit-isolated right atria. Thus, omega-CTX is a potent hypotensive agent in normotensive and hypertensive rabbits, predominantly via a peripheral sympatholytic action with no effect on vagal-cardiac efferent activity. However, it may affect the vagal component of the baroreceptor-HR reflex by an unknown central mechanism.

Animals↗
PubMed1995

Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.

1. Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child-bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and alpha-hydroxy-alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2. Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4-Hydroxy-alprazolam was the predominant metabolite in serum samples while alpha-hydroxy-alprazolam was not detected. 3. The mean oral clearance of alprazolam was 1.15 +/- 0.32 ml min-1 kg-1. The time course of alprazolam in milk roughly paralleled the perspective plasma time profile (mean serum residence time = 16.42 +/- 4.69 h; mean milk residence time = 18.93 +/- 7.03 h). The mean terminal half-life in serum was 12.52 +/- 3.53 h. 4. Observed milk/serum concentration ratios were determined in vivo as AUCmilk/AUCserum (mean M/S(obs) = 0.36 +/- 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

omega-Conotoxin GVIA and prazosin, but not felodipine, cause postural hypotension in rabbits.

1. The aim was to compare the effect of N-type calcium channel blockade by omega-conotoxin GVIA (omega-CTX) with alpha 1-adrenoceptor or L-type calcium channel blockade on postural adaptation in conscious rabbits. 2. Orthostatic responses were assessed by rapidly tilting the rabbits through 90 degrees for 1 min. Tilts were performed before, 30 and 60 min after i.v. bolus administration of vehicle (propylene glycol 0.17 mL/kg; n = 8), prazosin (0.5 mg/kg; n = 8), felodipine (30 micrograms/kg; n = 8) or omega-CTX (3 & 7 micrograms/kg; n = 9). 3. Prazosin, felodipine or omega-CTX caused significant falls in mean arterial pressure (MAP) with corresponding increases in heart rate (HR). Vehicle administration had no effect on MAP but caused a small fall in HR. 4. Before drug or vehicle administration, a small rise in MAP and HR occurred in response to tilt in all rabbits. In the vehicle treatment group, similar responses were observed to tilt at 30 and 60 min. Postural hypotension was observed in the prazosin treatment group, but not following administration of felodipine. Tilts 30 and 60 min after omega-CTX (3 micrograms/kg) caused an increase in HR but no change in MAP, different to the small pressor response observed following vehicle administration. However, following administration of omega-CTX 7 micrograms/kg (total dose, 10 micrograms/kg), significant falls in MAP with tachycardia were observed in response to tilt. 5. In conclusion, orthostatic hypotension was observed following acute alpha 1-adrenoceptor or N-type calcium channel blockade in the conscious rabbit. These findings are compatible with the expectation that agents which are directly sympatholytic interfere with postural adaptation. In contrast, L-type calcium channel antagonism with felodipine did not elicit postural hypotension.

Adrenergic alpha-Antagonists↗
PubMed1994

The effects of central administration of omega-conotoxin GVIA on cardiovascular parameters and autonomic reflexes in conscious rabbits.

1. The effects of central administration of omega-conotoxin GVIA (omega-CTX), an N-type calcium channel blocker, were examined in conscious rabbits implanted with lateral intracerebroventricular (i.c.v.) cannulae. 2. Experiments were performed over 4 consecutive days. On day 1, the baroreceptor heart rate (induced by glyceryl trinitrate and phenylephrine) and Bezold-Jarisch like (elicited by serotonin) reflexes were measured before (0 h) and 2 h after central administration of omega-CTX (3 or 30 pmol/kg, i.c.v.) or vehicle. On days 2-4, resting parameters and reflexes were again monitored but no further omega-CTX was administered. 3. No change in heart rate (HR) was observed in any rabbit treatment group during the experimental period. In the vehicle (n = 6) and omega-CTX 3 pmol/kg (n = 6) groups, small falls in mean arterial pressure (MAP) of 6 +/- 2 and 10 +/- 3 mmHg, respectively, occurred between 0 and 24 h; MAP then remained stable. Baroreceptor-heart rate reflex curve parameters did not change in either of these groups during the 4 day period. 4. Following administration of omega-CTX 30 pmol/kg (n = 7), MAP decreased progressively and by 48 h had fallen by 19 +/- 4 mmHg. Also at 48 h, a 20% decrease in HR range of the baroreceptor-heart rate reflex curve was seen without any change in the lower HR plateau from the 0 h control. This indicates that there was an attenuation of the sympathetically mediated upper component of the curve while the vagally mediated component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Excitatory amino acid receptors in membranes from cultured human retinal pigment epithelium.

The presence of specific, saturable receptor sites for excitatory amino acids (EAA) in membranes from cultured human retinal pigment epithelium (RPE) was established through the binding of [3H]L-glutamate (L-Glu). The age of the donors ranged from 6 days to 33 years. The affinity of the binding (KB) sites was between 1.2 and 1.5 microM, and did not change with the age of the donor, whereas the Bmax was slightly increased (8.6 to 13.0 pmol/mg) in membranes from the 33 year-old compared to the 29 day-old donor. The efficacy profile of agonists and antagonists acting at EAA receptors for displacing [3H]L-Glu was L-Glu = L-Aspartate > 2-amino-4-phosphonovalerate (AP5) > N-methyl-D-Aspartate (NMDA) > 1-aminocyclopentane-1,3 dicarboxylate (trans-ACPD) > 2-amino-3-phosphonopropionate (AP3). These data suggest the presence of either an NMDA-receptor sensitive to the metabotropic agonist trans-ACPD or alternatively, the presence of two different populations of receptors with similar affinity for the agonist: NMDA and metabotropic. Glycine highly stimulated Glu-binding; this effect was inversely related to the age of the donor. Taurine and to a lesser extent GABA, mimicked this effect. Stimulation by glycine was dose-dependent, insensitive to strychnine and 80% inhibited by 7-chlorokynurenate. This effect was also present in human RPE-derived fibroblasts, human scleral fibroblasts and the human lymphoblastoid cell line NB76, all continuously dividing cells. The results further support the possibility of the participation of EAA receptors in the regulation of phagocytosis in RPE.

Adolescent↗
PubMed1994

Histamine induced pulmonary vasodilatation in the rat: site of action and changes in chronic hypoxia.

Histamine constricts postcapillary lung vessels and also causes dilatation, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We wanted to determine a) whether vasoreactivity to histamine changes in chronic hypoxia; b) whether dilatation is due to H2 receptors; and c) which vessels dilate. We perfused isolated lungs of normal (C) and chronically hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstriction. To examine effects on arteries alone, we raised alveolar (inflation) pressure above outflow pressure; during inflation, pressure/flow (P/Q) lines were measured during normoxia, and hypoxia, and after histamine during continued hypoxia. Dose-related dilatation was seen, which was abolished by cimetidine and enhanced in CH rats. A mast cell-discharging agent, but not exogenous histamine, caused constriction, which was abolished by chlorpheniramine. P/Q lines differed in C and CH rats in a manner which suggests that hypoxia constricts larger "extra-alveolar" vessels in C rats, but mainly muscularized arterioles exposed to alveolar pressure in CH rats. Histamine restored the P/Q line to nearly its normoxic position; it therefore dilated those vessels which constrict in hypoxia in each rat group. It is concluded that histamine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hypertension.

Animals↗
PubMed1993

Taurine chloramine inhibits the synthesis of nitric oxide and the release of tumor necrosis factor in activated RAW 264.7 cells.

Taurine is present in high concentrations in most mammalian tissues, including those that prodigiously produce oxidants. Taurine protects against bronchiolar damage induced by NO2, ozone, bleomycin, and amiodarone. Taurine is chlorinated to form taurine chloramine (Tau-Cl) by the halide-dependent myeloperoxidase system and, under physiological conditions, reduces HOCl toxicity. Although NO and its metabolites, NO2- and NO3-, are thought to be major mediators of tissue damage resulting from oxidant exposure, cytokines, including tumor necrosis factor (TNF), are also involved. We examined the effects of Tau-Cl on NO production and TNF release by using RAW 264.7 cells activated with recombinant interferon-gamma (rIFN-gamma; 50 U/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). NO was measured spectrophotometrically as NO2- after reaction with Griess reagent and TNF was measured by ELISA. Tau-Cl (0.5 mM) inhibits NO and TNF released into the medium by 47% and 43%, respectively. Tau-Cl is actively transported into RAW 264.7 cells by an uptake system that is energy, temperature, and Na+ dependent. Competition experiments demonstrate that the uptake system for Tau-Cl is distinct from that for taurine. In addition, the NO synthase activity of cytosolic preparations from activated RAW 264.7 cells is irreversibly inhibited by pretreatment with Tau-Cl. We demonstrate that Tau-Cl inhibits production of NO and TNF by activated macrophages and suggest a mechanism through which taurine supplementation may protect against oxidant-induced tissue damage.

Amino Acid Oxidoreductases↗
PubMed1993

Glucose metabolism in mammalian cells as determined by mass isotopomer analysis.

A method using 13C isotopes and GCMS/SIM was developed and was used to study glucose metabolism in several mammalian cell lines. Using [U-13C6]glucose, the 13C isotopomer distributions in glucose, lactic acid, glutamic acid, aspartic acid, and gamma-aminobutyric acid produced by the cells were determined, and glycolysis, gluconeogenesis, and the flux into the amino acid pools were calculated. A 1:1 mixture of [U-13C6]glucose and [1-13C]glucose was used to examine the loss of 1-13C carbon from [1-13C]glucose via the pentose monophosphate pathway in the cells; this new method measures the production of [3-13C]lactic acid and [U-13C3]lactic acid, and thus avoids most systematic errors that result from the endogenous production of 12C-lactic acid during metabolic conversion; in addition, glycolysis and the recycling of glucose and lactic acid can be examined at the same time. The mass isotopomer analysis method is reproducible and sensitive, and can be used to analyze metabolites in 10(-7) M concentration with less than 10(5) cultured human cells. This method was used to examine metabolic regulation of glucose in fibroblasts, lymphoblasts, and PC12 cells under various conditions of metabolic disturbance. The method appears to have wide applicability for the study of metabolic regulation of glucose and metabolic defects in cells.

Animals↗
PubMed1993

Evaluating the special role of time in the control of handwriting.

Claims that time has a special role in the control of writing and the specific claim that writing time is absolutely invariant across changes in writing size are evaluated in two experiments. The first examined writing time for 24 undergraduate subjects who produced the string eyleyl with the dominant hand or arm in blocked repetitions having different vertical size targets. These variations produced small but systematic changes in writing time. The second experiment explored whether the small range of writing-time variation observed in experiment 1 was due to structural or strategic limitations. This experiment showed, for four undergraduate subjects, that writing time can be varied precisely across a wide range (0.6 to 1.66 of 'normal') while maintaining shape and vertical size constant. Taken together, these experiments suggest that, although relative stroke timing is approximately maintained, absolute timing is not critical to writing. The limited range of writing times typically observed should, rather, be ascribed to a strategic gradient that, along with other influences, broadly defines preferred writing times. This paper also describes a new application of Generalized Procrustes Analysis of shape, and this procedure is applied to the trajectories generated in both experiments. Although several small failures are noted, these analyses generally confirmed previous claims that shape is invariant across changes in writing time, size, and writing with the hand versus the arm. This result is a necessary buttress to the conclusions just described. Shape variability was also assessed in these analyses. This variability soared as writing time was reduced from normal, but showed only a small, insignificant increase as writing time was increased from normal. There were also small, predictable changes in spatial variability across changes in size and effector.

Adult↗
PubMed1993

Clinical pharmacokinetics of alprazolam. Therapeutic implications.

Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by hepatic microsomal oxidation, yielding alpha-hydroxy- and 4-hydroxy-alprazolam as principal initial metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma concentrations of the 4-hydroxy metabolite exceed those of the alpha-hydroxy derivative, but urinary recovery of alpha-hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be explained by chemical instability of 4-hydroxy-alprazolam in vitro. After single 1 mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a peak plasma concentration 12 to 22 micrograms/L occurring 0.7 to 1.8h postdose, a volume of distribution of 0.8 to 1.3 L/kg, elimination half-life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg. Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-independent and are unchanged during multiple-dose treatment. On average, mean steady-state plasma alprazolam concentrations change by 10 to 12 micrograms/L for each daily dosage change of 1 mg/day. Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender. Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced by the phase of the menstrual cycle in women. Coadministration of cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs alprazolam clearance. However, alprazolam clearance is not altered by coadministration of propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance may be impaired if alprazolam is coadministered. Alprazolam does not alter the pharmacokinetics of digoxin. Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 micrograms/L. Concentrations higher than this may be needed for suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness, sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in frequency with higher steady-state plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography.

The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.

Alpha-Globulins↗
PubMed1992

Crystallization and initial X-ray analysis of the C2-subunit of crustacyanin.

Crystals of the C2-subunit of crustacyanin have been grown from solutions containing ammonium sulphate and 2-methyl-2,4-pentanediol as co-precipitants. The crystals belong to space group P2(1)2(1)2(1) (a = 42.0 A, b = 80.9 A, c = 110.8 A) with two subunits per asymmetric unit and diffract beyond 2.2 A resolution.

Carrier Proteins↗