In and out of hot water: women in academic administration.
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Employment↗
Biomedical subjects
J M Davis
Publications and source records attributed to J M Davis.
Pulmonary failure and the production of leukotrienes.
The activation of neutrophils and elaboration of leukotrienes has a role in the pathophysiologic factors of many of the disease states seen by surgeons and nonsurgical counterparts. Although direct evidence of cause and effect is lacking, there is a growing array of literature proving the importance of neutrophils and LTB4 in the pathophysiologic factors of ARDS and MOF after significant illness or injury. Experimental and clinical data using alteration of arachidonic acid metabolism through drugs or diet should begin to accumulate to regulate the detrimental inflammatory response seen after severe illness or injury.
Animals↗
Communication strategies of adult cochlear implant candidates.
Adult cochlear implant candidates' abilities to cope with communication breakdown were assessed using the Communication Strategies Task (CST). Forty adult cochlear implant candidates with acquired hearing losses and 10 adults with normal hearing served as subjects. Appropriateness of responses to the CST were rated by 10 certified speech-language pathologists and audiologists. Seventy-six percent of the subjects demonstrated difficulty identifying onset or resolution of communication breakdown, communicators' feelings, factors contributing to communication breakdown, and appropriate repair strategies. The responses of individuals with sudden hearing losses did not differ significantly from the responses of individuals with progressive hearing losses. Response patterns did not correlate with the age of onset of the hearing loss, duration of deafness, age at the time of evaluation, or educational background. The results of this study suggest that ability to cope with communication breakdown must be evaluated on an individual basis.
Adaptation, Psychological↗
A skeptic's turn: memorial to a magnificent medical myth.
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Health Behavior↗
Hysteresis in the triple helix-coil transition of type III collagen.
A hysteresis is observed in the triple helix-coil transition of type III collagen. This hysteresis appears in the thermal transition, where it is not solvent-dependent, and also in the transition induced by guanidinium hydrochloride. The transitions are observed both by optical rotatory dispersion and by trypsin digestion. Experiments with various fragments of type III collagen, which, like the intact protein, contain a set of disulfide bonds at the carboxyl-terminal end, which functions as an effective nucleus for refolding, indicate that the hysteresis depends on the amino acid sequence, rather than being a general property of the triple helix. The carboxyl-terminal one-quarter fragment of type III collagen does not show a hysteresis, whereas a mutant type III collagen missing residues 595-1008 shows a hysteresis of the same magnitude as normal type III collagen. Several fragments were produced that are missing parts of the amino-terminal end, and these fragments show no hysteresis. The amino-terminal part of the triple helix of type III collagen consists of a stable region containing six Gly-Pro-Hyp tripeptide units within the first 16 tripeptide units. This region forms an amino-terminal clamp for the triple helix and, together with the set of disulfide bonds at the carboxyl-terminal end, allows for highly cooperative unfolding of the triple helix. The presence of this amino-terminal region is a prerequisite for the observed hysteresis.
Amino Acid Sequence↗
Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus.
The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5-HT1C receptors without causing a significant change in affinity (KD) of [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT1C receptors in brain. These results also suggest that 5-HT1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.
Animals↗
Homovanillic acid in the cerebrospinal fluid: patterns of response after four weeks of neuroleptic treatment.
Lumbar cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations were measured before and after 4 weeks of neuroleptic treatment in schizophrenic (n = 15) and schizoaffective (n = 4) patients. Neuroleptic treatment induced a nonsignificant (17%) increase in CSF HVA group mean levels. For the total group, no correlations were found between pretreatment CSF HVA and clinical measures, or between changes in HVA and clinical response. An alternative interpretation was attempted by defining "tolerant" and "nontolerant" subgroups. A "tolerant" response was defined as a reduction in posttreatment HVA values below pretreatment levels, whereas a "nontolerant" response was characterized by posttreatment values above pretreatment levels. When thus defined, nontolerant patients had a significantly inferior clinical response to neuroleptics, in contrast to their tolerant counterparts. Further, although there was no difference in pretreatment CSF HVA values between these two groups, pretreatment clinical profiles did differ significantly. Also, in a retrospective analysis, nontolerant patients were found to have a significantly earlier age of illness onset, a greater number of prior psychiatric hospitalizations, and more time spent in psychiatric hospitals.
Adult↗
Repeated cocaine administration does not affect 5-HT receptor subtypes (5-HT1A, 5-HT2) in several rat brain regions.
In order to examine whether cocaine-induced behavioral sensitization is modulated by changes in serotonin receptor subtypes, we measured the binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and of [3H]-ketanserin to 5-HT2 receptors in various brain regions of cocaine-treated and saline-treated (control) rats. As previously reported, repeated administration of cocaine resulted in behavioral sensitization. Stereotypic scores with the cocaine challenge were significantly (P < 0.05) higher in cocaine-pretreated animals than in the saline-pretreated group. Neither acute nor chronic cocaine administration significantly altered the number (Bmax) or the affinity (KD) of either [3H]8-OH-DPAT or [3H]ketanserin binding sites in any of the brain regions examined. These results suggest that the enhanced functional sensitivity of 5-HT1A or 5-HT2 receptor subtypes seen with cocaine may be associated with alterations in processes distal to receptors rather than changes in the number or the affinity of the receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Platelet serotonin-2 receptors in obsessive-compulsive disorder.
To examine the role of serotonin-2 (5-HT2) receptors in obsessive-compulsive disorder (OCD), we studied 5-HT2 receptors in platelets obtained from patients with OCD (n = 20) during a drug free baseline period, as well as in normal control subjects (n = 25). The maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 5-HT2 receptors were determined by receptor binding techniques using 125I-lysergic acid diethylamide (LSD) as radioligand. We observed that the mean Bmax of 125I-LSD binding in platelets of patients with OCD was not significantly different when compared with normal control subjects. There was also no significant difference in Kd values between patients with OCD and normal control subjects. To examine whether the baseline 5-HT2 receptors are related to the severity of illness, we determined the relationships of the baseline Bmax and Kd with baseline scores of the Hamilton Depression Rating Scale (HDRS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the National Institute of Mental Health (NIMH) Obsessive-Compulsive scale (GOCS). We found no significant correlation between baseline Bmax and Kd with the baseline HDRS, Y-BOCS, or NIMH-GOCS scores. Our results do not indicate abnormal 5-HT2 receptors in platelets of patients with OCD.
Adult↗
Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen.
Osteogenesis imperfecta (OI) is an inherited disease in which 90% of the cases result from mutations in the 2 genes, pro alpha 1 and pro alpha 2, coding for type I collagen. Type I collagen is a trimeric molecule, (alpha 1)2 alpha 2, which is dominated both structurally and functionally by the 300 nm triple-helical domain. Most OI mutations occur in this domain and almost all point mutations result in the substitution of other amino acids for the obligate glycine which occurs at every third residue. The phenotypic effects of these mutations are frequently attributed in part to alterations in the stability and rate of folding of the triple helix. In order to better understand the relationship between glycine substitutions and stability we review current concepts of the forces governing triple helical stability, denaturational and predenaturational unfolding, and the techniques of measuring stability. From observations on the stability of several collagen types as well as synthetic tripeptides, we present a model for stability based on the contribution of individual and neighboring tripeptide units to the local stability. Although in preliminary form, this empirical model can account for the observed shifts in the Tm of many of the point mutations described. The folding of the triple helix is reviewed. The involvement of peptidyl prolyl cis-trans isomerase in this process in vivo is demonstrated by the inhibition of collagen folding in fibroblasts by cyclosporin A. An hypothesis based on the relationship between the thermal stability at the site of mutation and the propensity for renucleation of folding is proposed.
Amino Acid Sequence↗
Serious sports injuries requiring hospitalization seen in a pediatric emergency department.
OBJECTIVE: To define the spectrum of serious sports injuries requiring hospitalization seen in a pediatric emergency department. DESIGN: Trauma registry and retrospective chart reviews. SETTING: Emergency department, Children's Hospital, Boston, Mass. STUDY PARTICIPANTS: One hundred forty-two patients with sports injuries presenting to the emergency department and requiring hospitalization over 2 years. MEASUREMENTS/RESULTS: Serious sports injuries accounted for 13% of admissions for trauma, 0.6% of visits to the emergency department for trauma, and approximately 0.14% of total encounters. Injuries included fractures (77%), abdominal injuries (7%), multiple trauma (5%), cerebral contusions or hemorrhages (4%), and dislocations (3%). The most frequently injured areas were the extremities (69%), head and neck (16%), and abdomen (3%). Compared with nonsports injuries requiring hospitalization, sports injuries occurred in older patients (11.5 vs 7.3 years, P < .001) and more often in males (83% vs 64%, P < .001). Sports injuries also resulted in higher Injury Severity Scores (10 vs 8.8, P = .021) and in more fractures (77% vs 51%, P < .001) and neck injuries (4% vs 1%, P = .002). CONCLUSION: Serious sports injuries evaluated in the emergency department affect predominantly male teenagers and result predominantly in fractures involving the extremities. The spectrum of injuries is dissimilar to that resulting from other mechanisms.
Adolescent↗
The risk of exposure of third-year surgical clerks to human immunodeficiency virus in the operating room.
The exposure of third-year medical students to blood and blood products in the operating room was assessed with a questionnaire distributed at the end of their clerkship in surgery. Sixty-six (68%) of ninety-seven students reported having been exposed to blood in the operating room during their 3-month rotation in surgery. During the year there was a decrease in the exposure rate that correlated with the students' knowledge of universal precautions (r = .96). Consistent with this observation was a significant decrease in the exposure rate from the first quarter of the year to the last quarter (88% vs 56% of the students). Of the 32 students stuck or cut in the operating room, 21 (66%) were injured by the surgeon. These data underscore the risk to medical students during their clerkships and the important role that universal precautions had in their protection.
Accidents, Occupational↗
Cocaine disposition in discrete regions of rat brain.
It has been proposed that various effects of psychoactive drugs on the central nervous system may be related to the capacity of the drug to selectively concentrate in specific regions of the brain. In rat brain, cocaine effects on striatal and nucleus accumbens dopaminergic systems show quantitative differences. However, the disposition of cocaine in various brain regions has not been reported. In the present studies we examined the cocaine concentrations over time in serum and discrete brain regions of the rat after single intraperitoneal (i.p.) injection. At different time points (5, 10, 20, 30, 60, 120, and 240 min) after i.p. injection of cocaine hydrochloride (10 mg kg-1, free base) the rats were decapitated and cocaine in serum and various brain regions was quantitated by a specific gas liquid chromatographic method. There was large inter-individual variability in different rats at each time-point. The disposition pattern of cocaine in rats after i.p. administration was similar to that observed in humans after intranasal administration. Initial absorption rate was rapid and, on average, the peak levels of cocaine were achieved in 10 min. The cocaine levels remained relatively high over the next 50 min indicating continual absorption, and then declined with a rate such that the levels 4 h after cocaine administration were undetectable in most of the animals. The overall changes in cocaine levels in various brain regions paralleled the serum concentrations. The area under the cocaine concentration-time curve (AUC) revealed more than three-fold differences in cocaine accumulation in various brain regions. This unequal disposition of cocaine may be responsible in part for differential biochemical effects in different brain regions.
Animals↗
Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model.
In order to evaluate further the physiological and inflammatory changes of meconium aspiration syndrome (MAS), 25 newborn piglets (1-2 days old, 1.5 +/- 0.4 kg) were studied. Piglets were briefly ventilated with 100% oxygen and then received an intratracheal bolus of 3 mL/kg of a 20% suspension of human meconium. They were then further ventilated, keeping PaCO2 at approximately 40 torr and PaCO2 at 70 torr during 4, 12, 24, and 48 h studies. Pulmonary function studies and tracheal aspirates were obtained at time zero and serially throughout the study. Bronchoalveolar lavage was performed at the end of the study to examine endogenous surfactant function. Control piglets received 3 mL/kg of intratracheal saline and were then ventilated for 48 h at an inspired oxygen concentration and mean airway pressure matched to the meconium treated group (to control for the effects of hyperoxia and barotrauma on the lung). MAS caused acute decreases in gas exchange and dynamic lung compliance, which returned toward baseline by 48 h (P < 0.001, ANOVA). Tracheal aspirate absolute neutrophil count, neutrophil chemotactic activity, albumin, and total protein concentrations also increased significantly over time (P < 0.001). Endogenous surfactant function appeared to be significantly inhibited by the meconium. All variables of lung injury were significantly higher in the meconium group compared to the saline control group over the 48 h study. Newborn piglets provide a clinically relevant model of MAS, demonstrating physiological and inflammatory changes with apparent alterations in endogenous surfactant function. Effective therapies for MAS may require interventions directed at all of these components of lung injury.
Animals↗
Asbestos fibers in parenteral medication.
The adequacy of current regulations for the control of particulate matter in injectable medicines has been brought into question by a recent television program which reported that asbestos fibers had been found in a number of such preparations. The fibers were identified as chrysotile, which occurs very widely as a secondary mineral in rocks, and is almost ubiquitous among minerals derived from natural erosion. Fibers are found in almost all drinking water and air samples unrelated to any contamination of fiber resulting from industrial exploitation. Because of this, even extreme laboratory precautions may fail to eliminate every fine fiber. A normal person living in an urban environment inhales about 10(5) asbestos fibers daily and ingests 10(10). There is evidence that a small proportion of these fibers regularly enters the circulation, and some fibers may be excreted in the urine. Elimination also occurs because retained chrysotile fibers fragment and disappear relatively quickly from human tissues, probably through macrophage action. Fiber length and dose are also important in disease causation. Established evidence on fiber length, durability, and quantitative exposure required for disease production does not indicate that the fibers reported to have been found in parenteral preparations constitute any hazard.
Asbestos↗
Power analysis for correlation of plasma level and clinical data.
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Antidepressive Agents↗
A family of wound-induced genes in Populus shares common features with genes encoding vegetative storage proteins.
Two wound-inducible cDNAs from poplar leaves show sequence identity to vegetative storage proteins (VSP) that accumulate seasonally in poplar bark tissues. We have compared the genomic organization, cDNA sequences and expression of the genes encoding the wound-inducible cDNAs (win4) with that of a bark VSP (called bark storage protein, or BSP). There appear to be several win4 genes in the poplar genome which segregate as a single locus and are therefore likely to be clustered. The same is true of the BSP genes. The win4 locus is linked (map distance of 5 cM) to the BSP locus, consistent with a common evolutionary origin of the genes. A near full-length win4 cDNA shows 75% sequence identity to BSP cDNAs. Both win4 and BSP are systemically wound-inducible; win4 transcripts accumulate in leaves and stems, whereas BSP transcripts accumulate almost exclusively in stems. A phloem transport-dependent signaling mechanism appears to be involved in systemic win4 expression after wounding. In contrast to BSP gene expression, win4 genes are not expressed in response to short day conditions. The data indicate win4 and BSP genes are differentially regulated, and their products may play important roles in the storage and reallocation of nitrogen in perennial plants.
Amino Acid Sequence↗
Renal and single-nephron function is comparable in thiobutabarbitone- and thiopentone-anaesthetised rats.
The thiobutabarbitone(TB, Inactin)-anaesthetised rat is an extremely widely used preparation for the study of renal function at the whole-organ and nephron levels. The recent withdrawal of TB from the market has made it essential to find an anaesthetic producing experimental conditions as similar as possible to TB to allow comparison of past and future data. Blood gas analysis, clearance and micropuncture studies were therefore performed in rats anaesthetised with TB or the related thiobarbiturate thiopentone (TP) (both 100 mg/kg body weight) to establish whether the latter meets this requirement. Both barbiturates caused similar transient respiratory depression and acidosis. Mean values (TP versus TB) over the total 8-h observation period for glomerular filtration rate (0.94 versus 1.05 ml/min), urine flow (3.8 versus 4.4 microliters/min) and K+ excretion (0.98 versus 1.18 mumol/min) were slightly lower (P < 0.05) in TP rats, whereas renal blood flow (6.26 versus 6.24 ml/min), filtration fraction (0.31 versus 0.34) and Na+ excretion (0.11 versus 0.098 mumol/min) did not differ. The single-nephron filtration rate (SNGFR) (42.1 versus 41.1 nl/min) and fractional reabsorption (42% versus 47%), both measured in the proximal tubule, did not differ, although in the TP group SNGFR rose with time (4.4%/h) whereas the fractional reabsorption did not change significantly; in the TB group SNGFR was constant but fractional reabsorption declined with time (1.5%/h). Fractional reabsorption up to the distal convoluted tubule declined with time, this was more pronounced in the TP group. SNGFR measured at this site did not differ between TP and TB (30.3 versus 30.1 nl/min) but increased with time with TP (2.7%/h).(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗