The impact of outreach.
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Biomedical subjects
Publications and source records attributed to L Davis.
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The effect of dexamethasone (0.1, 1, and 5 mg/kg/d given subcutaneously from d 14-18) was tested in infant mice continuously exposed from birth to either humidified air or 80% oxygen. Dexamethasone significantly decreased lung wet wt (p less than 0.01), lung water (p less than 0.021), lung dry wt, protein, and DNA (p less than 0.001) in both air- and oxygen-exposed animals. Dexamethasone, however, had no effect on lung compliance measured after animals were killed on d 18. It also had no effect on the increase in the blood-air barrier thickness or decrease in the blood-air exchange surface area seen in the 80% oxygen-exposed mice. Dexamethasone decreased thymus gland wt (p less than 0.001), body wt gain (p less than 0.001), brain wt (p less than 0.001), and lung lymphocytes (p less than 0.05) in both air- and oxygen-exposed animals. The effect of 1 mg/kg and 5 mg/kg of the drug could not be differentiated. During the 4 d of drug administration, one air- and one oxygen-exposed animal died; both received 5 mg/kg/d of dexamethasone; microscopic and culture evidence of infection was not found. If dexamethasone causes similar effects in human infants with bronchopulmonary dysplasia, it should be used with great caution even for short-term clinical management.
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The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway from the entorhinal cortex to the contralateral dentate gyrus and to compare the synapses of the sparse crossed pathway with those of the massive ipsilateral temporodentate pathway. The synapses of the crossed pathway were identified by using EM degeneration and EM autoradiographic techniques. For the degeneration studies, adult male Sprague-Dawley rats were killed 1, 2, or 4 days following a unilateral entorhinal cortex lesion and prepared for electron microscopy. To identify the synapses by using autoradiographic techniques, four animals received injections of 3H-proline into the entorhinal cortex, were allowed to survive for 3 days, and were prepared for EM autoradiography. Degenerating synapses of the crossed pathway that were found in the molecular layer of the dentate gyrus contralateral to a lesion formed asymmetric synapses on spines and possessed presynaptic organelles indistinguishable from synapses of the ipsilateral temporodentate pathway. The number of degenerating synapses was very low at all survival intervals (14.80 degenerating synapses/10,000 microns2 at 1 day postlesion and 1.95 degenerating synapses/10,000 microns2 at 2 days postlesion); no degenerating synapses were found at 4 days postlesion. Ninety-eight percent of the degenerating synapses found at 1 day postlesion exhibited electron-lucent degeneration. At 2 days postlesion 83% of the degenerating synapses in the dorsal blade and 18% of those in the ventral blade showed lucent degeneration; the remainder were electron dense. EM autoradiography confirmed the degeneration studies in terms of the type of terminals that were labeled and suggested that the density of the crossed pathway was higher than the degeneration results implied. We conclude that synapses of the crossed temporodentate pathway have a similar ultrastructure to synapses of the ipsilateral temporodentate pathway but exhibit a rapid form of degeneration such that they disappear very rapidly following the lesion.
The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway after they had sprouted to reinnervate the dentate gyrus following the destruction of the normal ipsilateral temporodentate pathway. The synapses of the sprouted crossed temporodentate pathway were identified at the EM level by using autoradiographic techniques and by evaluating the degeneration of the pathway following secondary lesions. Both EM autoradiography and EM degeneration revealed that the terminals of the sprouted crossed temporodentate pathway formed asymmetric synapses on spines; individual terminals appeared to make more synaptic contacts per terminal (multiple synapses) than in the case of the normal crossed pathway. In the two lesioned animals exhibiting the best labeling, labeled terminals made an average of 3.0 +/- 2.2 and 2.0 +/- 1.3 contacts per terminal. In contrast, labeled terminals in normal animals exhibited only one contact per terminal. The terminals of the sprouted pathway were also larger than those of the normal crossed pathway. The synapses of the crossed temporodentate pathway that degenerated after a secondary lesion of the entorhinal cortex exhibited both electron-lucent and electron-dense forms of degeneration at 2 days postlesion. In two animals that were quantitatively analyzed, the density of degenerating synaptic terminals was 281 and 218/10,000 microns2 in the terminal field of the sprouted crossed pathway. These values are much higher than in normal animals, where the density of degenerating synaptic terminals was only 2.12/10,000 microns2 at 2 days postlesion.(ABSTRACT TRUNCATED AT 250 WORDS)
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Recent studies have shown that protein synthetic machinery consisting of polyribosomes and associated membranous cisterns is selectively localized beneath synaptic sites on neurons. In the present paper, the role of this machinery in neuronal function will be considered. We will: 1. Summarize the studies that characterize the polyribosomes and define their associations with membranous cisterns. Taken together, these observations suggest the existence of a system for the synthesis and posttranslational processing of proteins at individual synaptic sites; 2. Review the evidence that the protein synthetic machinery is particularly prominent during the initial formation of synaptic contacts (during early development), and during lesion-induced synaptogenesis in mature animals. These observations have led to the hypothesis that the polyribosomes produce proteins that play a role in the formation of the synaptic junction; 3. Review evidence that supports the hypothesis that there is a local synthesis of protein within dendrites, as well as local glycosylation; 4. Describe the evidence suggesting that at least some of the protein constituents of the synaptic junction itself are synthesized locally; and 5. Describe our studies that reveal a mechanism for selective dendritic transport of RNA; this transport mechanism permits the delivery of RNA to postsynaptic sites throughout the dendritic arbor. We will advance the hypothesis that neurons position protein synthetic machinery together with the mRNA's that are appropriate for particular synapses beneath synaptic contact regions. At the synaptic site, this machinery could then direct the synthesis of particular proteins that are critical for synapse formation or maintenance. The positioning of protein synthetic machinery at postsynaptic sites permits a rapid local regulation of the production of key proteins by events at individual synapses.
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We compared the safety, efficacy, and side effects of induction of anesthesia with propofol (2.5 mg/kg), a new intravenous agent, and thiopental (4.0 mg/kg) in 62 patients in American Society of Anesthesiologists class I or II. There was no significant difference between induction times for the propofol (40.0 +/- 2.0 sec) and thiopental (44.0 +/- 4.0 sec) groups. Propofol administration produced a significant fall (P less than .05) in systolic blood pressure (SBP), from 134.1 +/- 2.6 mm Hg before injection to 128.3 +/- 2.4, 118.2 +/- 2.7, and 114.4 +/- 2.8 mm Hg one, two, and three minutes after injection, respectively. Diastolic blood pressure (DBP) fell significantly (P less than .05) during the three postinjection periods. Heart rate (HR) rose significantly (P less than .05), from 78.6 +/- 3.1 beats per minute before injection to 89.4 +/- 3.4 beats per minute one minute after injection. In patients given thiopental, SBP fell significantly (P less than .05), from 131.7 +/- 2.7 mm Hg before induction to 126.4 +/- 3.4 and 126.9 +/- 4.0 mm Hg two and three minutes after injection, respectively. The DBP did not change significantly in the thiopental group, but the HR rose significantly (P less than .05), from 73.3 +/- 2.8 beats per minute before injection to 83.9 +/- 3.0, 90.1 +/- 2.3, and 84.2 +/- 2.4 beats per minute one, two, and three minutes after injection, respectively. In 94% of patients given propofol, there were apneic periods of more than 60 seconds, compared to 50% in the thiopental group (P less than .05). There was a significant difference (P less than .05) between groups for the incidence of pain on injection; 31% of the patients receiving propofol had pain, compared to 3% of those receiving thiopental.
The monoclonal antibody MUD50 recognizes a group of developmentally regulated proteins, which are almost exclusively expressed by prespore cells in developing aggregates of Dictyostelium discoideum. Some of these antigens are integrally associated with the cell membrane, as assessed by physical and detergent-fractionation procedures. The MUD50-reactive proteins are glycosylated and some are phosphorylated. Post-translational modification is the common antigenic feature that is recognized by the MUD50 antibody in these cell-type-specific proteins. A glycosylation-defective mutant, DL118, (modB) does not express the MUD50 epitope, but does express the MUD52 epitope, which is found on a different group of glycoproteins. Therefore, we conclude that MUD50 recognizes a particular carbohydrate epitope on a restricted group of proteins. These proteins are structurally diverse, but are apparently involved in the maintenance of structure and movement of the multicellular D. discoideum slug.
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DNA sequence analysis of the gene coding for the variant protein, factor IXLong Beach (FIXLB), has identified a transition mutation in an otherwise normal factor IX (FIX) gene. Genomic DNA clones spanning 35 kilobase (kb) pairs of the FIXLB gene were isolated. A gene analysis strategy that specifically characterized exons and their flanking intron sequences predicted the entire amino acid sequence of FIXLB. A thymine to cytosine transition causes the substitution of a threonine codon (ACA) for an isoleucine codon (ATA) in exon VIII of the FIXLB gene. This mutation results in an amino acid substitution at residue 397 of the FIX zymogen and the phenotypic display of hemophilia-B. Previous studies revealed that activated purified FIXLB (FIXaLB) had normal Ca2+, phospholipid, and factor VIIIa binding characteristics. However, FIXaLB activated factor X or factor VII (with their cofactors Ca2+ and phospholipid) at significantly reduced rates, suggesting that the defect in FIXaLB lies near or within the catalytic triad of the FIX heavy chain. Identification of an amino acid substitution near the carboxy-terminus of the FIXaLB heavy chain supports the earlier characterization of this variant protein. Moreover, our data identify a residue in the catalytic domain of FIXa essential for normal function.
Cisplatin (cis-platinum, 100 mg/m2) and fluorouracil (1000 mg/m2/d), for 120 hours' infusion every three weeks for three courses, produced a 93% overall response rate and a 54% complete clinical response at the single-institution level. The same combination was tested in the Radiation Therapy Oncology Group to evaluate the effectiveness and feasibility of this combination. An overall response rate of 86% was obtained, with a 38% complete clinical response. Only 27 of 42 patients completed planned surgery. Compliance with chemotherapy and radiation therapy was substantially better. No additional morbidity after surgical resection or postoperative radiation therapy was identified as secondary to the induction chemotherapy. We conclude that the combination of cisplatin and fluorouracil infusion is effective, with high complete clinical response rate in patients with advanced, previously untreated head and neck carcinoma.
The effectiveness of analgesic medication for post-surgical pain was surveyed in a surgical ward of a large general hospital. Since earlier studies have shown that pain generally decreases rapidly and is negligible by the fourth day after surgery, the patients in the survey were assigned to 2 groups: those given analgesics during the first 4 days after surgery, and those given analgesics for pain after the fourth day. The results show that the patients with pain that persists beyond day 4 comprise a substantial proportion of the patients in a surgery ward (31%), are older, tend to use more words to describe their pain, and are helped less by their prescribed analgesic medications. This group is prescribed lower doses of analgesics and receives them more frequently; however, this prescription strategy appears to be ineffective since 26% of these patients report increased pain after medication compared to only 2% in the group that received analgesics during the first 4 days.