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Biomedical subjects

E Wood

Publications and source records attributed to E Wood.

At least 73 records · Page 4Linked to original sources

Association of phosphorylated insulin-like growth factor-I receptor with the SH2 domains of phosphatidylinositol 3-kinase p85.

Insulin-like growth factor-I (IGF-I) stimulates the production of 3-inositides and markedly increases the phosphatidylinositol 3-kinase activity that is immunoprecipitated by anti-phosphotyrosine antibodies, a portion of which is also associated with the IGF-I receptor. In this study, recombinant p85, the regulatory subunit of phosphatidylinositol 3-kinase, and fusion proteins containing various subdomains were used to investigate the association of p85 with the IGF-I receptor and to demonstrate that p85 is a direct in vitro substrate of the IGF-I receptor kinase. Solubilized IGF-I receptor was immobilized on antireceptor antibody-agarose beads. Following in vitro receptor phosphorylation and incubation with cell lysate, immobilized receptor became associated with phosphatidylinositol 3-kinase activity and with protein bands with molecular masses of 85 and 110 kDa, which correspond to the known molecular masses of the subunits of phosphatidylinositol 3-kinase. These associations were inhibited by the addition of recombinant intact p85 or SH2-containing fusion proteins, but not by fusion proteins containing its SH3 domain or breakpoint cluster homology region. A fusion protein containing the SH2 domains of Ras GTPase-activating protein also inhibited the association of phosphatidylinositol 3-kinase activity with immobilized IGF-I receptor, although less effectively than p85, whereas a similar construct containing the SH2 domain of pp60src was without effect. When immobilized phosphorylated IGF-I receptor was incubated with intact p85 or the SH2-containing fusion proteins, it became associated with and phosphorylated these proteins. These results demonstrate that at least in vitro, a tight association occurs between phosphorylated IGF-I receptor and phosphatidylinositol 3-kinase, that the region of phosphatidylinositol 3-kinase that contains its SH2 domains is directly involved in this association, and that this region is a direct substrate for IGF-I receptor tyrosine kinase. Furthermore, these results suggest that Ras GTPase-activating protein can also interact with the IGF-I receptor and that different SH2 domain-containing proteins interact with the IGF-I receptor with widely differing affinities.

Animals↗

Adjustment disorders of sleep: the sleep effects of a major stressful event and its resolution.

Seventy volunteers had 3 nights of sleep recordings during a period of marital separation, and 61 returned for repeat studies 1 year later. At that time, the divorce was final for 42. Forty of the volunteers were depressed when first screened, and 30 were not. Initially all those undergoing marital separation had less delta sleep than an age-matched married comparison sample. Delta increased at followup for those whose divorce was completed. Rapid eye movement (REM) latency was reduced and REM percent was elevated only in the depressed. Among the not depressed, those whose divorces remained incomplete at the followup had lower delta, higher REM percent, and shorter REM latency than did those whose divorces were finalized. This suggests that prolonged emotional stress may put these subjects at some risk for a mood disorder.

Adaptation, Psychological↗

Biphasic striatal dopamine release during transient ischemia and reperfusion in gerbils.

To clarify the nature of ischemic striatal dopamine release during the earliest periods of neuronal injury, we used chronoamperometry to measure dopamine levels every 60 seconds during various durations of ischemia in 32 gerbils. Catecholamine-selective electrodes were implanted into the brains of anesthetized gerbils subjected to 2, 5, or 10 minutes of transient forebrain ischemia or permanent forebrain ischemia. Four control animals showed a stable chronoamperometric baseline. In the six gerbils subjected to permanent ischemia, dopamine release was rapid during early ischemia and slowed with time. The four animals subjected to 2 minutes of ischemia showed minimal dopamine release. The six gerbils subjected to 5 minutes of ischemia demonstrated a noticeable dopamine release during ischemia, and three of the six developed a massive secondary dopamine release during reperfusion. All six animals subjected to 10 minutes of ischemia demonstrated a similar biphasic dopamine release twice the size of that observed in the 5-minute group. Pretreatment with pargyline in six additional gerbils subjected to 10 minutes of ischemia failed to modify significantly this biphasic pattern of dopamine release. We conclude that dopamine release occurs very early during ischemia and that its magnitude correlates with the duration of an ischemia insult. Reperfusion is associated with an even larger striatal dopamine release. This previously unreported biphasic dopamine release phenomenon may have important clinical implications in the management of cerebral ischemia.

Animals↗

REM latency and the recovery from depression: getting over divorce.

OBJECTIVE: The authors' goal was to address five questions: 1) What is the frequency of early REM sleep in subjects in the process of divorce who meet diagnostic criteria for major depressive disorder? 2) What is the frequency of this sign in subjects in the process of divorce who are not depressed? 3) How often does this sign persist following remission of depressive symptoms? 4) What is the predictive value of early REM sleep among depressed subjects for later adjustment to the process of divorce? and 5) What is the role of a family history of depression or alcoholism in the presence and persistence of early REM sleep? METHOD: Two hundred fourteen volunteers undergoing marital separation were recruited; 70 of these subjects were selected for a 3-night sleep study. Forty of the 70 subjects met criteria for depression and 30 did not; 61 (87%) returned for repeat studies 1 year later. RESULTS: Fifteen (38%) of the 40 depressed subjects had short REM latency. Seven of these continued to have short REM latency 1 year later, but none of these met the criteria for depression at that time. A higher proportion of these subjects had made a good adjustment to their new life than did depressed subjects whose initial and follow-up REM latencies fell within the normal range. CONCLUSIONS: These data suggest that depressed individuals with normal REM latency may need more aggressive treatment intervention.

Adult↗

Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications.

The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU.

Costs and Cost Analysis↗

The biochemical basis of tolerance to malathion in Rhodnius prolixus.

1. LC50 of malathion, fenitrothion and lindane were determined in R. prolixus and T. infestans. R. prolixus was shown to be tolerant to malathion. 2. The penetration rate of (14C)-malathion into R. prolixus and T. infestans was similar. 3. Acetylcholinesterase from R. prolixus heads was 3.3-fold less sensitive to inhibition by malaoxon than the similar enzyme of T. infestans. 4. R. prolixus showed more activity of GSH-S-transferases against DCNB than T. infestans. 5. The in vitro degradation of (14C)-malathion demonstrated that R. prolixus is more active than T. infestans in carboxyester splitting to give alpha and beta monoacids. 6. The synergism of TPP and TOCP on malathion toxicity was higher in R. prolixus than in T. infestans. 7. Esterase activity against alpha and beta naphthyl acetates proved to be much lower in R. prolixus homogenates than in T. infestans homogenates. An inverse result was observed when PTA was the substrate.

Acetylcholinesterase↗

Long-term survival in an infant with urethral atresia.

Complete urethral atresia is an anomaly that previously was incompatible with life. We report on a surviving infant with this anomaly. As a fetus urinary decompression was accomplished with a vesicoamniotic shunt. Peritoneal dialysis was initiated shortly after birth and at 9 months supramembranous scrotal inlay urethroplasty was performed to provide for egress of urine from the bladder. A maternal renal allograft was performed when he was 12 months old. When the patient was 3 1/2 years old he had normal renal function and emptied the bladder to completion through the reconstructed urethra. Although mildly delayed, he continues to progress with all developmental milestones.

Cystostomy↗

Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study.

Early morning salivary 17 alpha-hydroxyprogesterone (17-OHP) determination differentiates patients with non-classical 21-hydroxylase deficiency (NC21OHD) from those who are not affected. Using this test, we have conducted a trial screening study for NC21OHD and have compared the study results with previously reported figures for the frequency of this disorder. Testing was performed on 258 subjects recruited from among the medical students and employees of the New York Hospital-Cornell Medical Center. In 2 of the 249 admissible subjects, the 0700-0900 h salivary 17-OHP level was within the range for NC21OHD patients (0.72-6.7 nmol/L; n = 8). These 2 individuals were subsequently confirmed to be affected by ACTH testing. Of the subjects with morning salivary 17-OHP levels below the cut-off point of 0.72 nmol/L, 29 were recalled for ACTH testing and were confirmed to be unaffected. Prevalence of NC21OHD in the test population was determined according to ethnic group. Our study gives a prevalence by screening of 1.14% among caucasians, which agrees with values of 0.81% and 1.06% obtained by different analytical methods. Further, both affected subjects were Ashkenazi Jews, and the prevalence of 3.23% among study members from this group concurs with increased rates of 3.64% and 4.97% already reported. On the basis of a small population sample, screening so far confirms the claim that NC21OHD is the most common autosomal recessive human disorder. Using values from ACTH-proven unaffected subjects (n = 47) and NC21OHD patients (n = 10), we establish preliminary normative data for morning salivary 17-OHP levels of 0.172 nmol/L for unaffected subjects (95% confidence interval, 0.05-0.54 nmol/L) and 1.76 nmol/L for NC21OHD-affected subjects (95% confidence interval, 0.42-7.32 nmol/L).

17-alpha-Hydroxyprogesterone↗

An update on the frequency of nonclassic deficiency of adrenal 21-hydroxylase in the Yugoslav population.

Nonclassic steroid 21-hydroxylase deficiency is an attentuated adrenal enzyme defect that is commonly the basis of hyperandrogenic syndromes. Inherited as an autosomal recessive trait, it is known to occur with high frequency in the general population and with increased frequency in a number of ethnic groups, including the Yugoslav population. Following expansion of the original data on 21 families in Croatia to a total of 49 Croatian and Serbian families, we establish that this enzymatic disorder is increased in this Slavic population and provide an updated estimate for the gene frequency of 0.092 (0.035-0.149). Also in keeping with earlier reports, we continue to note the absence of association between nonclassic 21-hydroxylase deficiency occurring among Yugoslavs and HLA-B14; DR1.

17-alpha-Hydroxyprogesterone↗

Assay of pyrethroid-hydrolysing esterases using (1,R)-cis-3-(2,2-dibromovinyl)-2,2-dimethyl cyclopropane carboxylates as substrates.

1. p-Nitrophenyl-, alpha-naphthyl-, and beta-naphthyl-(1,R)-cis-3-(2,2-dibromovinyl)2,2-dimethyl cyclopropane carboxylates are proposed as pyrethroid-like substrates for the detection of pyrethroid esterases (PyEs). 2. The substrates have been used in a spectrophotometric assay of PyEs and in a staining method to locate PyEs on polyacrylamide electrophoresis.

Animals↗

Effect of reductions in respiratory therapy on patient outcome.

In 1981-1982, a Massachusetts Hospital Association and Massachusetts Blue Cross-Blue Shield task force reviewing ancillary services found that the use of respiratory therapy at New England Deaconess Hospital far exceeded the statewide average. These findings led to a hospital-wide effort to reduce ancillary services. As part of this effort, we studied the effect of the reductions in respiratory therapy on patient outcome. At the beginning of the study, senior respiratory therapists advised physicians about the optimal use of various respiratory-therapy services, including their discontinuation when no longer necessary. One year after the intervention began, we analyzed the use of respiratory therapy by employing data-collection techniques that were identical to those used by the task force. Marked reductions in all categories of respiratory therapy had occurred, but morbidity and mortality from pulmonary disorders had not increased. In the largest group studied--patients undergoing coronary-artery bypass surgery--the charges for respiratory therapy, the length of hospital stay, and pulmonary complications had all decreased. We conclude that consistent application of prescribed guidelines for respiratory therapy results in marked decreases in its use and that such decreases can be achieved without a reduction in the quality of care.

Boston↗

Colonic motility and enema spreading.

Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents.

Adult↗

Whole-bowel transit in patients with the irritable bowel syndrome.

The transit of radiolabelled preparations through the stomach, small intestine and colon was monitored in ten patients with the irritable bowel syndrome. Five patients complained of diarrhoea, and five complained of constipation. The preparations comprised a non-disintegrating capsule and a multiparticulate system. Both preparations emptied from the stomach together and at the same rates in both groups of patients. In the patients complaining of constipation, the transit times through the small intestine were the same for both preparations. In the patients complaining of diarrhoea, the capsule passed through the small intestine slightly faster than the particles, but there were no significant differences in the small-intestinal transit rates of the two patient groups. Within the colon, the transit of the capsule was faster than that of the small particles. Although movement through the colon was, on average, faster in the group of patients complaining of diarrhoea, there was considerable intersubject variability, and the differences in transit rates between the two patient groups were not statistically significant.

Adult↗

Distribution and properties of glutathione S-transferase from T. infestans.

The glutathione transferase from T. infestans is able to render aqueous metabolites when incubated in vitro with malathion, parathion and fenitrothion. It is a soluble enzyme present in every developmental stage and widely distributed in all insect organs. The purification procedure applied, consisting of fractionation with ammonium sulfate and Bio-Gel P-60 chromatography, gives an unique molecular form catalytically active using methyl iodide as substrate in polyacrylamide gel electrophoresis (PAGE). One of the most active substrates is the 1-chloro-2,4-dinitrobenzene (CDNB), with an activity maximum at pH 7.5 and at 45 degrees C temperature. Its activation energy calculated from an Arrhenius plot is 14,846 cal mol-1. The enzyme susceptibility to inhibition by thiol reagents shows three degrees of responses; slight, moderate or high, depending on the compounds used. The kinetics of the enzyme catalysed reaction with the purified fraction is complex, and resembles that reported for glutathione S-transferase A from rat liver, showing a biphasic kinetic mechanism in which the reaction pathway depends on the concentration of GSH. In general, the properties of this insect enzyme are similar to those enzymes isolated from vertebrate organisms.

Animals↗

Drug delivery to the proximal colon.

The transits of a capsule and a multiparticulate pellet system have been monitored through the gastrointestinal tract in six healthy volunteers. Both preparations moved together through the stomach and small intestine, reaching the colon, on average, 4 h after dosing. Within the colon the pellets dispersed and moved at a slower rate than the capsule. There was considerable intersubject variability in the large bowel transit times. The findings are discussed in terms of drug delivery to the colon.

Adult↗

The legume-Rhizobium symbiosis: a cell surface interaction.

This review will examine the early stages of infection of legume roots by strains of Rhizobium that induce nitrogen-fixing nodules. The object is to show that, at least in terms of ultrastructure, the interactions between the plant and the rhizobia occur at the cell surface interface between these organisms. This situation exists at all stages, from the time the bacteria attach to the surface of the root hairs to the time they occur as the nitrogen-fixing form in the cytoplasm of the nodule cells, enclosed by peribacteroid membranes.

Cell Adhesion↗

Relationship of conceptus number to the action of luteinizing hormone-antiserum in the pregnant rat.

Treatment of pregnant rats on Day 12 of pregnancy with luteinizing hormone-antiserum (LH-AS) (equine anti-bovine LH) had no effect on the maintenance of pregnancy or serum progesterone levels in rats bearing either 2 or more than 8 conceptuses. In rats with only 1 conceptus, LH-AS administration resulted in a significant decline in serum progesterone to basal levels within 24 h and all animals (n = 6) failed to maintain pregnancy. All rats with either 1, 2 or greater than 8 implantations showed no effect of normal horse serum (NHS) administration. There was no effect of LH-AS administration on serum testosterone levels, compared to NHS-treated controls.

Animals↗