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Biomedical subjects

L Davis

Publications and source records attributed to L Davis.

At least 19 recordsLinked to original sources

Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression.

The biology of mood disorders involves gamma-aminobutyric acid (GABA), a neurotransmitter whose levels in plasma likely reflect brain GABA activity. Previous research has shown that a subset of patients with primary unipolar major depression have low plasma GABA levels, which parallels findings from studies of cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients with primary unipolar depression. Plasma levels of GABA were stable over this time. For the group, mean plasma GABA levels on follow-up did not change significantly from entry levels. Plasma GABA levels measured on follow-up were significantly (p < .001) correlated with entry levels. Patients with low plasma GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on follow-up, and patients with plasma GABA levels in the control range (> or = 100 pmol/ml) at entry similarly remained in this category (chi 2 = 7.23, p = .007). This was true whether or not the patient had recovered from depression on follow-up. Levels of plasma GABA did not significantly correlate with severity of depression at either entry (p = .40) or follow-up (p = .52), nor was there a significant correlation between change in plasma GABA and change in the 17-item Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These data are consistent with the notion that plasma GABA is independent of clinical state in patients with primary unipolar depression. Low plasma GABA may be a trait marker of illness in a subset of patients with mood disorder.

Adult

2-Amino-3-ketobutyrate-CoA ligase from beef liver mitochondria: an NMR spectroscopic study of low-barrier hydrogen bonds of a pyridoxal 5'-phosphate-dependent enzyme.

A study of protons associated with low-barrier hydrogen bonds in 2-amino-3-ketobutyrate-CoA ligase (AKB-ligase, EC 2.3.1.29) by NMR is reported. Three resonances are observed in the range of delta H = 15-20 ppm when the NMR spectrum of AKB-ligase is recorded at 600 MHz. These low-barrier hydrogen bonds are associated respectively with a side chain proton, the PLP pyridinium ring nitrogen proton, and the PLP Schiff base proton at the active site of the ligase. The pyridinium proton has been assigned a chemical shift of 19.10 ppm and the Schiff base proton 14.90 ppm. The third low-barrier hydrogen bond associated proton resonating at 16.20 ppm is assigned to a proton of a side chain group. All three resonances disappear when pyridoxal phosphate is removed from the ligase. Consistent with NOE coupling, the side chain group proton should be close to the proton of the Schiff base nitrogen of the pyridoxal 5'-phosphate. The effects of temperature, pH, substrate, and NOE on the three resonances are also studied, in order to assign the protons. The three low-barrier hydrogen bonds described in this report may serve to anchor the cofactor in the active site of 2-amino-3-ketobutyrate-CoA ligase.

Acetyltransferases

An SH3 domain is required for the mitogenic activity of microinjected phospholipase C-gamma 1.

Phospholipase activity is elevated in dividing cells. In response to growth factor stimulation, phospholipase C-gamma (PLC-gamma) binds to activated tyrosine kinase receptors via SH2 binding domains, resulting in phosphorylation of PLC-gamma and activation of its enzyme activity. These observations suggest that PLC-gamma participates in the signal transduction pathway employed by growth factors to promote mitogenesis. Consistent with this hypothesis, microinjection of purified bovine PLC-gamma into quiescent fibroblasts has been previously reported to initiate a mitogenic response [Smith et al. (1989) Proc. Natl. Acad. Sci. 86, 3659]. We have reproduced this result using recombinant rat PLC-gamma protein. Surprisingly, however, a catalytically inactive mutant of PLC-gamma, H335Q, also elicited a full mitogenic response. The capacity to induce mitogenesis by microinjection of PLC-gamma was mapped to the 'Z' domain of the protein, which contains PLC-gamma's SH2 and SH3 motifs. Inactivation of the phosphorylated tyrosine binding properties of both SH2 domains had no effect on the mitogenic activity of the Z-domain peptide. However, deletion of the SH3 domain resulted in a complete loss of activity. These results suggest that PLC-gamma's mitogenic properties do not require the enzyme's phospholipase activity, but are instead mediated by a novel pathway for mitogenic stimulation which is dependent upon an intact SH3 domain.

3T3 Cells

A Project Alpha program for smaller chapters.

Smaller chapters cannot easily adapt to their groups the projects of larger chapters or programs at the national level. To address this problem, the Coosa Valley chapter of AORN, Rome, Ga, developed a program that offers perioperative experience to nursing students at a local college. Members of the chapter act as preceptors for the students and educate them before the students' preceptorships in the OR. This education seems to relieve some of the intimidation and fear related to the OR, and students in the program are more willing to participate in the program.

Curriculum

Comparative analysis of mouse NotI linking clones with mouse and human genomic sequences and transcripts.

NotI cleavage sites are frequently associated with CpG islands that identify the 5' regulatory sites of functional genes in the genome. Therefore we analyzed a sample of 22 NotI linking clones prepared from mouse brain DNA, to determine whether these mouse NotI site associated clones could be used for comparative analysis of mouse and human genomes by cross-reaction with both mouse and human genomic DNA and RNA in Southern and Northern hybridization. We further examined whether we could establish the identity of these clones with known genes by comparing the nucleotide sequences surrounding the NotI site with the GenBank database. We observed that 70% of the clones cross-hybridized with human DNA and that 4 of 11 tested clones (36%) detected a transcript in human HeLa cells RNA whereas 73% clones (8/11) detected transcripts in mouse RNAs from one or more organs. Single pass sequence analysis was successful on 16 of 19 clones. The GC content in these sequence was very high (48.8% to 73.8%) suggesting that 12 of 16 sequenced clones contained a CpG island. Three out of 19 clones showed significant similarity with previously analyzed mouse gene sequences in GenBank, including the mouse rRNA gene family, cathepsin and the scip POU-domain genes. In addition, two sequences showed significant similarity to the human and rabbit protein phosphatase 2A-beta subunit and the human transforming growth factor-beta. Thus, 5 of 16 clones showed homology with identified genes. These results and the recent work of using RLGS methods for genetic mapping indicate that NotI linking clones can be used to efficiently cross reference a comparative analysis of the mouse and human genomic maps.

Animals

Race, control, mastery, and caregiver distress.

This study investigated the relationship between race, psychological resources of sense of control and caregiver mastery, and distress outcomes of caregiver depression and role stain among 77 African American and 138 White spouse caregivers of persons with dementia. Patterns of association between psychological resources and caregiving distress outcomes varied by type of outcome. Sense of control had a direct negative relationship with depression. Caregiver mastery moderated the effects of stressors on depression and was the only significant psychological resource predicting role strain. Although African American caregivers were less likely to report caregiver depression and role strain, there were no race differences in the process influencing caregiver distress.

Aged

Using a group-oriented contingency to increase social interactions between children with autism and their peers. A preliminary analysis of corollary supportive behaviors.

The effects of a group-oriented contingency on the social and supportive interactions of three preschoolers with autism and their socially competent peers were examined. Children participated in daily manipulative play activities in groups of three (including one target child and two peers). A group reinforcement contingency increased all three target children's social interactions with peers (e.g., share, assistance, and play organizers) but produced few or no corollary supportive exchanges within the playgroups (e.g., one socially competent youngster tells another to "Ask [target child] to share the Lego toys with us"). After a withdrawal of treatment phase in which social interactions decreased to low levels, children were taught to direct supportive comments to other members of their playgroups. Following this brief training, the interdependent group contingency was reinstated to reinforce the share, assistance, and play organizer exchanges between the target children and peers. In addition to interacting with the target children, socially competent youngsters also used supportive prompts to facilitate the social exchanges between their remaining group members. Children's social and supportive interactions decreased and increased again during subsequent baseline and group contingency phases. These results are discussed with regard to the efficacy of group-oriented contingencies and the function of supportive peer behaviors.

Autistic Disorder

Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis.

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.

Adolescent

Preparative in situ hybridization: selection of chromosome region-specific libraries on mitotic chromosomes.

We have developed preparative in situ hybridization (Prep-ISH) of complex DNA populations to mitotic chromosomes as a means of generating chromosome region-specific DNA subpopulations. Prep-ISH is a combination of two cytogenetic techniques: in situ hybridization of DNA molecules to mitotic chromosomes and chromosome microdissection. Here, we present test cases demonstrating the feasibility of this approach on mouse and human genomes, using single nuclei, single chromosomes, or single chromosomal subregions to assess sensitivity, specificity, and representation of the Prep-ISH technique. Prep-ISH has a number of applications in studies of gene expression and genome organization, including efficient cytogenetic sorting of tissue-specific cDNAs and genomic DNA libraries. In addition, Prep-ISH is likely to dramatically reduce the number of candidate genes to aid in gene discovery efforts and to improve efficiency of developing transcription maps and YAC and cosmid contigs through defined cytogenetic regions.

Animals

Purification and structural characterization of porcine L-threonine dehydrogenase.

L-Threonine dehydrogenase was purified 10,000-fold to a specific activity approximately 300 mumol.min-1.mg-1 protein from porcine liver mitochondria. Purification to apparent homogeneity was achieved by sequential chromatography on DEAE Sepharose FF, Affi-Gel Blue, Sephacryl S-200, Matrex Gel Red A, and Matrex Gel Green A. The subunit molecular mass was estimated as 37 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, while an apparent native molecular mass of 73 kDa was shown by gel filtration chromatography, suggesting a dimeric structure. The purified enzyme was subjected to proteolytic degradation and the resulting peptides were isolated exclusively by reverse-phase high-performance liquid chromatography. Approximately 70% of the total sequence was obtained and the N-terminal amino acid sequence of the intact polypeptide chain was thus tentatively extended to residue 40.

Alcohol Oxidoreductases

Application of the 3M microvascular anastomotic device in non-vascular tubular structures.

In this study, the 3M microvascular anastomotic system was utilized for the first time to perform an end-to-end anastomosis in a non-vascular tubular structure, which was compared to the conventional microvascular suture method. The bicornuate rat uterus was the preferred structure because of its anatomic similarity to the human fallopian tube. Thirty Sprague-Dawley rats underwent 3M and conventional end-to-end anastomoses of their bicornuate uteri. At different intervals, the animals were explored and biopsies were taken for examination under light microscopy. Overall patency rate with the 3M technique was 68 percent vs. 96 percent with the conventional technique. Complication rates were 40 percent with the 3M device and 12 percent with the conventional method. This study concludes that, if this method is to be used on non-vascular tubular structures, further modifications to the system and additional research are mandatory, in order to recommend this technique for clinical application.

Anastomosis, Surgical