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Biomedical subjects

C R Davis

Publications and source records attributed to C R Davis.

At least 19 recordsLinked to original sources
PubMed2007

2,3,7,8-Tetrachlorodibenzo-p-dioxin affects fluctuating asymmetry of molar shape in mice, and an epistatic interaction of two genes for molar size.

Fluctuating asymmetry (FA), random variation between left and right sides in a bilaterally symmetrical character, is a commonly used measure of developmental instability that is expected to increase with increasing environmental stress. One potential stressor is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a powerful toxicant known to disturb tooth development. In this study, mice in the F(2) generation produced from an intercross between two inbred strains (C57BL/6J and AKR/J) were exposed in utero to TCDD. We hypothesized that TCDD would increase FA in the molars of exposed mice over that of the control mice. In addition, we hypothesized that we would discover genes for molar size, shape or asymmetry whose expression would be affected by TCDD. We detected a very small, but significant, increase in FA of molar shape (but not size) in the TCDD-exposed mice compared to the control mice, although molar size and shape did not differ between these groups. Although we did not uncover any genes that acted differently in the TCDD exposed and control groups, we did identify two genes whose dominance by additive epistatic effect on molar size was affected by TCDD. We concluded that although TCDD may be affecting the expression of some genes governing the development of molars in our population of mice, FA of molar size and shape is not a particularly sensitive indicator of this effect.

Animals↗
PubMed2006

Absence of neurotoxic effects in leopard sharks, Triakis semifasciata, following domoic acid exposure.

Domoic acid (DA), a potent neurotoxin produced by select species of algae and diatoms, kills neurons bearing kainic acid-type glutamate receptors. Studies have shown that DA bioaccumulates in invertebrates and fish that consume the diatoms. In every vertebrate species tested or observed in the wild, dietary or systemic DA causes neuronal damage or clinical signs of neurotoxicity. Sharks, like marine birds and mammals, are exposed to DA through their diet; however, no research has demonstrated the effect of DA on shark behavior or physiology. In this study, juvenile leopard sharks (Triakis semifasciata) were given DA by intracoelomic injection at doses of 0, 1, 3, 9, and 27 mg/kg and observed for 7 days. The sharks failed to demonstrate behavioral or histological changes in response to the toxin. We identified putative brain glutamate receptors by probing western blots with an antibody specific for kainic acid-type glutamate receptors and demonstrated receptor localization in the cerebellum with immunohistochemistry. Blood levels of DA in three sharks dosed at 9 mg/kg fell rapidly within 1.5h of injection. We show that leopard sharks possess the molecular target for DA but are resistant to doses of DA known to be toxic to other vertebrates.

Animals↗
PubMed2000

Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice.

Leptin is a 16 kD protein that is produced by adipocytes and induces weight loss in both normal and genetically obese ob/ob mice. ob/ob mice are obese, have multiple metabolic abnormalities, and exhibit impaired wound healing. Exogenous administration of leptin to these animals induces weight loss and corrects their metabolic defects. Leptin's effect on wound repair, however, has not been studied. Systemic administration of leptin at doses ranging from 0.1 to 10 mg/kg/day induced a highly significant acceleration in wound repair in ob/ob mice (p<0.0001), but not in db/db mice, indicating that leptin's effects on wound repair were mediated through the leptin receptor. We then investigated the possibility that leptin was acting directly at the wound site by administering leptin topically, and found that topical leptin also induced a dose dependent acceleration in wound repair (p<0.0001). In addition, we found that all forms of leptin receptor, including the signal transducing long form, were present in skin by RNase protection assay, and that leptin receptor localized to subcutaneous vessels of wounded skin by in situ hybridization. Finally, we investigated the possibility that leptin stimulated angiogenesis in wounds by analyzing wound hemoglobin and wound vessel density. Neither systemic nor topical leptin induced any significant changes in either parameter, suggesting that leptin accelerates wound repair by a mechanism other than stimulation of angiogenesis. In summary, both systemic and topical leptin accelerate wound repair in diabetic ob/ob mice, possibly via the direct interaction of leptin with its receptors in wounded skin, but do not appear to significantly stimulate wound angiogenesis. Further studies to better elucidate the mechanisms of leptin's effects on wound repair are warranted.

Administration, Topical↗
PubMed1999

Association of plasma IgM with body size, histopathologic changes, and plasma chemistries in adult Pacific herring Clupea pallasi.

Pacific herring Clupea pallasi immunoglobulin is an IgM-like molecule comprised of heavy and light chains with molecular weights of 79 and 25 to 27 kD, respectively. Purified immunoglobulin was used to generate highly specific polyclonal antibodies for development of a sandwich ELISA. The ELISA was used to quantify total plasma IgM in 602 Pacific herring captured in Prince William Sound and Sitka Sound, Alaska, USA. Plasma IgM concentrations ranged from 0.13 to 5.32 mg ml-1. Using multiple stepwise regression analysis, plasma IgM was highly correlated (p < or = 0.01) with body length, Ichthyophonus hoferi infection, plasma albumin, plasma cholesterol, liver macrophage aggregates, and focal skin reddening. I. hoferi was the only organism significantly associated with plasma IgM. Gender, site, and season (spring vs fall) did not contribute to significant differences in plasma IgM. This study contributes to the understanding of the interaction of body size, plasma chemistries, and pathological changes upon circulating immunoglobulins in fish.

Alaska↗
PubMed1999

Lovastatin biosynthesis in Aspergillus terreus: characterization of blocked mutants, enzyme activities and a multifunctional polyketide synthase gene.

BACKGROUND: Lovastatin, an HMG-CoA reductase inhibitor produced by the fungus Aspergillus terreus, is composed of two polyketide chains. One is a nonaketide that undergoes cyclization to a hexahydronaphthalene ring system and the other is a simple diketide, 2-methylbutyrate. Fungal polyketide synthase (PKS) systems are of great interest and their genetic manipulation should lead to novel compounds. RESULTS: An A. terreus mutant (BX102) was isolated that could not synthesize the nonaketide portion of lovastatin and was missing a approximately 250 kDa polypeptide normally present under conditions of lovastatin production. Other mutants produced lovastatin intermediates without the methylbutyryl sidechain and were missing a polypeptide of approximately 220 kDa. The PKS inhibitor cerulenin reacted covalently with both polypeptides. Antiserum raised against the approximately 250 kDa polypeptide was used to isolate the corresponding gene, which complemented the BX102 mutation. The gene encodes a polypeptide of 269 kDa containing catalytic domains typical of vertebrate fatty acid and fungal PKSs, plus two additional domains not previously seen in PKSs: a centrally located methyltransferase domain and a peptide synthetase elongation domain at the carboxyl terminus. CONCLUSIONS: The results show that the nonaketide and diketide portions of lovastatin are synthesized by separate large multifunctional PKSs. Elucidation of the primary structure of the PKS that forms the lovastatin nonaketide, as well as characterization of blocked mutants, provides new details of lovastatin biosynthesis.

Amino Acid Sequence↗
PubMed1999

Hepatic sarcocystosis in a horse.

Hepatic sarcocystosis was diagnosed in a horse in association with refractory bacterial osteomyelitis and plasma cell tumor of the maxilla and hepatic salmonellosis. Gross lesions included pleural, pericardial, and peritoneal effusions, hepatomegaly, gastric ulceration, colonic edema, and proliferative tissues filling 2 maxillary dental alveoli. Histologically, liver was characterized by severe suppurative, necrotizing, periportal hepatitis, and severe periacinar necrosis. Hepatocytes frequently contained protozoal schizonts in various stages of development. In mature schizonts, merozoites were often arranged radially around a central residual body, consistent with asexual division by endopolygeny. Ultrastructural features of merozoites included an apical conoid and polar ring, anterior micronemes, central nuclei, and absence of rhoptries. These protozoa did not react to antisera raised against Neospora caninum, Sarcocystis neurona, Toxoplasma gondii, or Hammondia hammondi. The microscopic and ultrastructural characteristics and immunoreactivity of this organism are consistent with a Sarcocystis sp. other than S. neurona. This is the first report of Sarcocystis-associated hepatitis in a horse. The life cycle of this organism and source of infection are unknown.

Animals↗
PubMed1998

Analysis of the mechanisms of action of the Saccharomyces cerevisiae dominant lethal cdc42G12V and dominant negative cdc42D118A mutations.

The Saccharomyces cerevisiae Cdc42p GTPase is localized to the plasma membrane and involved in signal transduction mechanisms controlling cell polarity. The mechanisms of action of the dominant negative cdc42(D118A) mutant and the lethal, gain of function cdc42(G12V) mutant were examined. Cdc42(D118A,C188S)p and its guanine-nucleotide exchange factor Cdc24p displayed a temperature-dependent interaction in the two-hybrid system, which correlated with the temperature dependence of the cdc42(D118A) phenotype and supported a Cdc24p sequestration model for the mechanism of cdc42(D118A) action. Five cdc42 mutations were isolated that led to decreased interactions with Cdc24p. The isolation of one mutation (V44A) correlated with the observations that the T35A effector domain mutation could interfere with Cdc42(D118A, C188S)p-Cdc24p interactions and could suppress the cdc42(D118A) mutation, suggesting that Cdc24p may interact with Cdc42p through its effector domain. The cdc42(G12V) mutant phenotypes were suppressed by the intragenic T35A and K183-187Q mutations and in skm1Delta and cla4Delta cells but not ste20Delta cells, suggesting that the mechanism of cdc42(G12V) action is through the Skm1p and Cla4p protein kinases at the plasma membrane. Two intragenic suppressors of cdc42(G12V) were also identified that displayed a dominant negative phenotype at 16 degrees C, which was not suppressed by overexpression of Cdc24p, suggesting an alternate mechanism of action for these dominant negative mutations.

Amino Acid Sequence↗
PubMed1997

Endoscopic retrograde cholangiopancreatography in the treatment of bile leaks and bile duct strictures after laparoscopic cholecystectomy.

We reviewed our experience over 3 years with 11 patients who had bile leaks (Group 1) and 8 patients who had bile duct strictures after laparoscopic cholecystectomy (LC) and were treated with endoscopic retrograde cholangiopancreatography (ERCP) (Group 2). In Group 1, bile leaks were at the level of the cystic duct in 10 patients and from a duct of Luschka in 1 patient; 10 patients had sphincterotomy and 11 patients received barbed stents. All patients had resolution of bile leak and stents were removed after an average of 5 weeks. In Group 2, stenoses were at the level of the common bile duct (CBD) in 7 patients and of the CBD-common hepatic duct in 1 patient. Six patients had a sphincterotomy and 7 patients were successfully treated with pneumatic polyethylene balloon dilatation and stent placement. One patient had unsatisfactory dilatation and was referred to surgery. Two patients had permanent resolution of stenosis at 3 and 4 years of follow-up, 5 patients had recurrence, and a total of 6 patients eventually needed surgery. We conclude that ERCP is effective in resolving isolated bile leaks, but iatrogenic strictures after LC more often require surgical treatment after ERCP.

Bile↗
PubMed1996

Cardiac Depression Scale: validation of a new depression scale for cardiac patients.

Assessing the effect of interventions on quality of life in cardiac patients lacks sensitivity because there is no specifically validated scale for measuring depression in cardiac patients. A questionnaire of 35 items (selected for face validity) was given to 246 cardiac outpatients (age 59.3 +/- 14.1 years, 159 male, 87 female). The Beck Depression Scale was then administered, followed by blinded clinical rating of depression. The item scores were subjected to common factor analysis. Internal consistency was assessed using alpha reliability coefficients and clinical validity using Spearman correlation coefficients. The final scale consisted of 26 items (alpha reliability coefficient 0.90) in 2 robust dimensions and 7 subscales. The scale correlated well with clinical rating and with the Beck Depression Scale, but without the marked skewness of the latter. The behavior of the new Cardiac Depression Scale suggests that it will be an excellent measure for studies of outcome in cardiac patients.

Adaptation, Psychological↗
PubMed1995

Molecular characterization of the proline-1 (pro-1) locus of Neurospora crassa, which encodes delta 1-pyrroline-5-carboxylate reductase.

delta 1-pyrroline-5-carboxylate reductase (P5CR; [L-proline: NAD(P+) 5-oxidoreductase]; EC 1.5.1.2) catalyzes the final step in proline biosynthesis. We have shown that the proline-1 (pro-1) locus of Neurospora crassa encodes P5CR. The pro-1 gene was localized to a 3.2 kb region by complementation of (restoration of proline-independent growth to) a proline auxotroph carrying a recessive mutation at the pro-1 locus. The nucleotide sequence of this 3.2 kb region contains an open reading frame with coding capacity of 311 amino acids. The deduced polypeptide shows significant similarity to P5CR amino acid sequences. Similarity of N. crassa P5CR is greatest to that of the yeast, Saccharomyces cerevisiae, but is also strong to P5CR sequences from archaea, eubacteria, plants, and humans. In N. crassa, amino acid imbalance, including deficiency or excess of a single amino acid, such as histidine, induces expression of many amino acid biosynthetic genes that are under cross-pathway control, a general regulatory system analogous to general amino acid control in Saccharomyces. Although P5CR catalyzes the only committed step in proline biosynthesis, pro-1 expression was unaltered by histidine starvation and independent of CPC1, a positively acting transcription factor that mediates cross-pathway control in N. crassa.

Alleles↗
PubMed1994

Novel sensor technology for monitoring and control of critical plant nutrient parameters.

A novel dielectric sensor technology has been developed for monitoring and control of plant nutrient delivery systems as part of NASA's Controlled Ecological Life Support System (CELSS) program. A unique measurement phenomenon was discovered in which the electrostatic field is shunted to a third terminal of the sensor, resulting in a much greater sensitivity to changes in the complex dielectric properties of the nutrient solution. Based on this phenomenon, a small, flexible, thin-film shunting dielectric sensor (SDS) was designed to provide low-frequency, non-invasive measurement of both the thickness and nutrient concentration of the layer of solution on a plant growth surface. Test results indicate a sensitivity of +/- 0.05mm in layer thickness while characterization of the ability to measure nutrient concentration continues. The development plan for this sensor is presented and other applications are discussed.

Algorithms↗
PubMed1994

Correlation of the physical and genetic maps of the centromeric region of the right arm of linkage group III of Neurospora crassa.

We have cloned three linked genes serine-1 (ser-1), proline-1 (pro-1) and acetate-2 (ace-2) that lie near the centromere on the right arm of linkage group III (LGIIIR) of Neurospora crassa. The ser-1 gene was cloned by sib selection. A chromosomal walk that spans 205 kilobases (kb) was initiated from ser-1. Complementation analysis with clones isolated during the walk allowed identification of the pro-1 and ace-2 genes. Restriction fragment length polymorphism analysis has confirmed the localization of ser-1, pro-1 and ace-2 to the centromeric region of LGIIIR. Genetically, we measured 1% recombination between ser-1 and pro-1 and 2% recombination between pro-1 and ace-2. Physical distances for these intervals were 114 kb from ser-1 to pro-1 and 36 kb from pro-1 to ace-2. Thus, for the pro-1 to ace-2 interval we calculate a physical/genetic correlation of 18 kb/map unit (mu) whereas, in the immediately adjacent, centromere-proximal interval from ser-1 to pro-1, we calculate 114 kb/mu. This provides evidence for a centromere effect, a decrease in recombination frequency as one approaches the centromere.

Centromere↗
PubMed1992

Characterization of the formate (for) locus, which encodes the cytosolic serine hydroxymethyltransferase of Neurospora crassa.

Serine hydroxymethyltransferase (SHMT) occupies a central position in one-carbon (C1) metabolism, catalyzing the reaction of serine and tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate. Methylenetetrahydrofolate serves as a donor of C1 units for the synthesis of numerous compounds, including purines, thymidylate, lipids, and methionine. We provide evidence that the formate (for) locus of Neurospora crassa encodes cytosolic SHMT. The for+ gene was localized to a 2.8-kb BglII fragment by complementation (restoration to formate-independent growth) of a strain carrying a recessive for allele, which confers a growth requirement for formate. The for+ gene encodes a polypeptide of 479 amino acids which shows significant similarity to amino acid sequences of SHMT from bacterial and mammalian sources (47 and 60% amino acid identity, respectively). The for+ mRNA has several different start and stop sites. The abundance of for+ mRNA increased in response to amino acid imbalance induced by glycine supplementation, suggesting regulation by the N. crassa cross-pathway control system, which is analogous to general amino acid control in Saccharomyces cerevisiae. This was confirmed by documenting that for+ expression increased in response to histidine limitation (induced by 3-amino-1,2,4-triazole) and that this response was dependent on the presence of a functional cross-pathway control-1 (cpc-1) gene, which encodes CPC1, a positively acting transcription factor. There are at least five potential CPC1 binding sites upstream of the for+ transcriptional start, as well as one that exactly matches the consensus CPC1 binding site in the first intron of the for+ gene.

Amino Acid Sequence↗
PubMed1986

Growth and Metabolism of Lactic Acid Bacteria during and after Malolactic Fermentation of Wines at Different pH.

Commercially produced red wines were adjusted to pH 3.0, 3.2, 3.5, 3.7, or 4.0 and examined during and after malolactic fermentation for growth of lactic acid bacteria and changes in the concentrations of carbohydrates, organic acids, amino acids, and acetaldehyde. With one exception, Leuconostoc oenos conducted the malolactic fermentation in all wines and was the only species to occur in wines at pH below 3.5. Malolactic fermentation by L. oenos was accompanied by degradation of malic, citric, and fumaric acids and production of lactic and acetic acids. The concentrations of arginine, histidine, and acetaldehyde also decreased at this stage, but the behavior of hexose and pentose sugars was complicated by other factors. Pediococcus parvulus conducted the malolactic fermentation in one wine containing 72 mg of total sulfur dioxide per liter. Fumaric and citric acids were not degraded during this malolactic fermentation, but hexose sugars were metabolized. P. parvulus and species of Lactobacillus grew after malolactic fermentation in wines with pH adjusted above 3.5. This growth was accompanied by the utilization of wine sugars and production of lactic and acetic acids.

Journal Article↗
PubMed1984

Computer-Aided analysis of human esophageal peristalsis. I. Technical description and comparison with manual analysis.

Manual and computer analysis of esophageal peristaltic activity induced by swallows of 5ml water were compared in 6 healthy subjects under basal conditions and following i.v. injection of 4 pharmacological agents: edrophonium (E, 0.08mg/kg), atropine (A, 0.6mg), pentagastrin (PG, 0.6mcg/kg), and glucagon (GL, lmcg). Esophageal manometry was performed using a low compliance perfusion system and recorded on paper for standard manual analysis. The signal was concurrently taped on an analog recorder for subsequent digitization and analysis on a PDP-11 computer using a locally developed program. With both methods we determined the wave amplitude, duration, average upward slope (dP/dT), and velocity of wave progression. In addition, the computer allowed calculation of area under each wave and maximum upward slope (Max dP/dT). We found no significant difference between results of the parameters measured using both methods. Wave amplitude was significantly increased by E and significantly decreased by A. Average upward slope was decreased and velocity was significantly increased only by A. Computer-calculated wave area and Max dP/dT were significantly changed by both E and A. PG and GL had no effect on any of the measured parameters of the peristaltic wave. Esophageal peristalsis can be analyzed using a computer-aided method, providing a rapid and objective measurement of classical parameters and access to more in-depth analysis.

Adult↗
PubMed1984

Kaposi's sarcoma and autoimmune thrombocytopenia.

Outbreaks of Kaposi's sarcoma, opportunistic infections, and autoimmune thrombocytopenia among homosexual men have recently been described. We report here a case with the combination of Kaposi's sarcoma and autoimmune thrombocytopenia. Our patient presented with Kaposi's sarcoma limited to the integument and autoimmune thrombocytopenia diagnosed by elevated platelet bound IgG. Characteristics of immunosuppression included lymphocytopenia and a reversed blood helper:suppressor T lymphocyte ratio. Immunohistochemical evaluation of skin biopsy specimens revealed tumor cells to contain Factor VIII-related antigen (a vascular endothelial cell marker). In addition some tumor cells stained positively with a monoclonal antibody directed against a cytomegalovirus antigen.

Adult↗