Search PubMed⌕ Search

Biomedical subjects

K R Davis

Publications and source records attributed to K R Davis.

At least 37 records · Page 2Linked to original sources

Ozone-induced responses in Arabidopsis thaliana: the role of salicylic acid in the accumulation of defense-related transcripts and induced resistance.

Exposure of Arabidopsis thaliana to ozone results in the expression of a number of defense-related genes that are also induced during a hypersensitive response. A potential common link between the activation of defense gene expression during a hypersensitive response and by ozone treatment is the production of active oxygen species and the accumulation of hydrogen peroxide. Here we report that salicylic acid accumulation, which can be induced by hydrogen peroxide and is required for the expression of both a hypersensitive response and systemic acquired resistance, is also required for the induction of some, but not all, ozone-induced mRNAs examined. In addition, we show that ozone exposure triggers induced resistance of A. thaliana to infection with virulent phytopathogenic Pseudomonas syringae strains. Infection of transgenic plants expressing salicylate hydroxylase, which prevents the accumulation of salicylic acid, or npr1 mutant plants, which are defective in the expression of systemic acquired resistance at a step downstream of salicylic acid, demonstrated that the signaling pathway activated during ozone-induced resistance overlaps with the systemic acquired resistance activation pathway and is salicylic acid dependent. Interestingly, plants expressing salicylate hydroxylase exhibited increased sensitivity to ozone exposure. These results demonstrate that ozone activates at least two distinct signaling pathways, including a salicylic acid dependent pathway previously shown to be associated with the activation of pathogen defense reactions, and that this latter pathway also induces a protective response to ozone.

Arabidopsis↗

Treatment of prolactin-secreting macroadenomas with the once-weekly dopamine agonist cabergoline.

Dopamine agonist administration is the primary therapy for macroprolactinomas, but bromocriptine is the only agent approved in the United States. Its use is limited by a high incidence of side effects, a short duration of action, and a lack of effectiveness in some patients. Cabergoline is a long-acting dopamine agonist specific for the D2 receptor that is more effective and better tolerated than bromocriptine in women with microadenomas or idiopathic hyperprolactinemia. However, experience with cabergoline in the treatment of patients with macroadenomas is limited. We report the first study of chronic administration of cabergoline conducted exclusively in patients with macroprolactinomas. Fifteen patients (8 women, 7 men) ages 18-76 yr were studied in an open-label 48-week dose escalation trial of cabergoline administered once per week. Eleven patients had received prior therapy with other dopamine agonists. Mean prolactin (PRL) levels decreased by 93.6%, and normal levels were attained in 73% of patients at doses of 0.5-3.0 mg per week. Three of five patients who had failed to normalize PRL on prior dopamine agonists achieved normal levels. Gonadal function was restored in all hypogonadal men and in 75% of premenopausal women with amenorrhea. Tumor size decreased in 11 of the 15 patients. Side effects were minimal. Of the 5 patients who had experienced side effects in prior dopamine agonists, 4 had none on cabergoline, and the fifth had milder symptoms. During two further years of follow up, the improvement in PRL levels, gonadal function, and tumor size has persisted during cabergoline administration, and three patients have experienced a further decline in PRL and/or tumor size. This study demonstrates the effectiveness and minimal side effects of once-weekly cabergoline for treatment of macroprolactinomas.

Adenoma↗

Isolation of a novel Arabidopsis ozone-induced cDNA by differential display.

We have used a reverse transcriptase polymerase chain reaction procedure (differential display) to isolate cDNAs corresponding to transcripts that accumulate in ozone-treated Arabidopsis thaliana. In this report we describe the characterization of an ozone-induced transcript, AtOZI1. AtOZI1 mRNA in untreated plants was detected at low levels in cotyledons, leaves, and flower buds and at higher levels in roots and mature flowers. AtOZI1 mRNA accumulation was transiently induced in leaves 3- to 5-fold within the first 6 h of ozone treatment. AtOZI1 mRNA accumulation was also transiently induced 3- to 6-fold by phytopathogenic Pseudomonas strains. Sequence analysis of AtOZI1 revealed that it encodes a 8.6 kDa basic protein that contains a putative signal peptide and two potential phosphorylation sites. Our results suggest that AtOZI1 represents a novel stress-related protein that accumulates in response to the production of active oxygen species.

Amino Acid Sequence↗

The phenylalanine ammonia-lyase gene family in Arabidopsis thaliana.

Phenylpropanoid derivatives are a complex class of secondary metabolites that have many important roles in plants during normal growth and in responses to environmental stress. Phenylalanine ammonialyase (PAL) catalyzes the first step in the biosynthesis of phenylpropanoids, and is usually encoded by a multi-gene family. Genomic clones for three Arabidopsis thaliana PAL genes containing the entire protein-coding region and upstream and downstream sequences have been obtained and completely sequenced. Two A. thaliana PAL genes (PAL1 and PAL2) are structurally similar to PAL genes that have been cloned from other plant species, with a single intron at a conserved position, and a long highly conserved second exon. Previously identified promoter motifs plus several additional sequence motifs were found in the promoter regions of PAL1 and PAL2. Expression of PAL1 and PAL2 is both qualitatively and quantitatively similar in different plant organs and under various inductive conditions. A third A. thaliana PAL gene, PAL3, differs significantly from PAL1 and PAL2 and other sequenced plant PAL genes. PAL3 contains an additional intron, and its deduced amino acid sequence is less homologous to other PAL proteins. The PAL3 promoter region lacks several sequence motifs conserved between A. thaliana PAL1 and PAL2, as well as motifs described in other genes involved in phenylpropanoid metabolism. A. thaliana PAL3 was expressed at very low levels under the conditions examined.

Arabidopsis↗

The Arabidopsis thaliana 4-coumarate:CoA ligase (4CL) gene: stress and developmentally regulated expression and nucleotide sequence of its cDNA.

An Arabidopsis cDNA clone encoding 4-coumarate:CoA ligase (4CL), a key enzyme of phenylpropanoid metabolism, was identified and sequenced. The predicted amino acid sequence is similar to those of other cloned 4CL genes. Southern blot analysis indicated that 4CL is single-copy gene in Arabidopsis. Northern blots showed that 4CL expression was activated early during seedling development. The onset of 4CL expression was correlated with the onset of lignin deposition in cotyledons and roots 2-3 days after germination. The timing of the expression of a parsley 4CL1-GUS fusion in transgenic Arabidopsis seedlings was examined in parallel and was very similar to that of endogenous 4CL. In mature plants, highest 4CL expression was observed in bolting stems, where relatively large amounts of lignin accumulate. Both 4CL and 4CL1-GUS mRNA accumulation was strongly and transiently activated by wounding of mature Arabidopsis leaves. 4CL expression was specifically activated within 6 h after infiltration of Arabidopsis ecotype Columbia leaves with a Pseudomonas syringae pv. maculicola strain harboring the bacterial avirulence gene avrB, which causes in incompatible interaction. The timing of 4CL activation was identical to the previously observed activation of PAL gene expression in this interaction. No activation of 4CL expression was observed in a compatible interaction caused by a Pseudomonas syringae pv. maculicola strain without avrB.

Amino Acid Sequence↗

Recombinant beet curly top virus genomes exhibit both parental and novel pathogenic phenotypes.

Recombinant genomes derived from the Logan and CFH strains of the geminivirus beet curly top virus (BCTV) have been constructed and analyzed for pathogenicity on Nicotiana benthamiana and sugar beet (Beta vulgaris L.). Infectivity assays indicated that the latent period on N. benthamiana was primarily determined by a DNA fragment bearing the leftward open reading frames (ORFs) L1, L2, L3, and L4. Recombinants bearing leftward ORFs from the CFH strain were characterized as having a short latent period (mean = 6-11 days), while the reciprocal recombinants bearing leftward ORFs from the Logan strain had latent periods defined as long (mean = 16-22 days). Infectivity assays on sugar beet indicated that certain recombinant BCTV genomes exhibited novel pathogenic properties not common to either wild type strain, including the loss of systemic movement and replication competency, or asymptomatic systemic infection of sugar beet. The results indicate that N. benthamiana is a more permissive host than sugar beet with respect to heterologous combinations of BCTV genes, and that pathogenicity and virulence of BCTV in sugar beet requires the interaction of certain viral gene products and/or cis-elements that have coevolved in the same strain.

Biological Transport↗

Identification of loci in Arabidopsis that confer resistance to geminivirus infection.

The infection of susceptible plant hosts by single-stranded DNA viruses in the geminivirus group depends on the interaction of host and viral factors for the replication of viral DNA, the expression of viral genes, and the movement of virus throughout the plant. This paper reports that two strains of the geminivirus, beet curly top virus (BCTV) differ in their ability to infect certain ecotypes of Arabidopsis thaliana. Symptoms appeared on susceptible plants approximately 2-3 weeks after inoculation with BCTV-Logan and after 10-15 days with BCTV-CFH. Symptoms were more severe in BCTV-CFH-infected plants and included leaf curling, the formation of stunted, deformed inflorescence structures and the accumulation of anthocyanin pigments in symptomatic tissues. Analysis of viral DNA accumulation indicated that symptom development and severity were correlated with the amount of viral DNA present in the plants. Viral DNA was undetectable in two ecotypes that were phenotypically resistant to BCTV-Logan. Studies of viral DNA replication in excised inflorescence pieces demonstrated that BCTV-Logan could replicate in tissues from these resistant ecotypes, suggesting that resistance was due to a block in viral movement. Genetic studies of these two ecotypes indicate that resistance is due to a single, recessive locus. This is the first example of a single resistance locus to any geminivirus. The identification of resistant and susceptible interactions between different BCTV strains and A. thaliana ecotypes provides an excellent model system for the genetic and molecular analysis of the interaction of a plant host with this important group of plant pathogens.

Arabidopsis↗

An Arabidopsis thaliana lipoxygenase gene can be induced by pathogens, abscisic acid, and methyl jasmonate.

We isolated and characterized a 2.8-kb, full-length, Arabidopsis thaliana cDNA clone encoding a lipoxygenase. DNA sequence analysis showed that the deduced amino acid sequence of the Arabidopsis protein is 72 to 78% similar to that of legume seed lipoxygenases. DNA blot analysis indicated that Arabidopsis contains a single gene, LOX1, with appreciable homology to the cDNA clone. RNA blot analysis showed that the LOX1 gene is expressed in Arabidopsis leaves, roots, inflorescences, and young seedlings. LOX1 expression levels were highest in roots and young seedlings. In mature plants, LOX1 mRNA levels increased upon treatment with the stress-related hormones abscisic acid and methyl jasmonate and remained high for at least 96 h. Expression of the LOX1 gene was examined following infiltration of leaves with virulent (Psm ES4326) and avirulent (Pst MM1065) strains of Pseudomonas syringae. LOX1 mRNA levels were induced approximately 6-fold by both virulent and avirulent strains; however, the response to avirulent strains was much more rapid. Infiltration of leaves with Pst MM1065 resulted in maximal induction within 12 h, whereas maximal induction by Psm ES4326 did not occur until 48 h. When a cloned avr gene, avrRpt2, was transferred to Psm ES4326, LOX1 mRNA accumulated in a pattern similar to that observed for the avirulent strain Pst MM1065.

Abscisic Acid↗

Skull base dumbbell tumor: surgical experience with two adolescents.

Pediatric skull base tumors are rare and until recently were considered unresectable. We present two patients with tumors of similar anatomic position with an extracranial component in the infratemporal fossa and parapharyngeal space, an isthmus at the foramen ovale, and a superior component in the middle cranial fossa in the region of the cavernous sinus. A 15-year-old girl experienced contiguous spread of a spindle cell sarcoma; an 18-year-old boy developed a chondrosarcoma. A middle fossa approach provided the advantage of surgical avoidance of structures such as the middle ear and mastoid, facial nerve, and mandible. Postoperative recovery was rapid. Our impression is that preoperative carotid artery occlusion and a middle fossa approach for tumor resection can be performed in a young patient with acceptable morbidity and at least short-term benefit. Surgery can, therefore, provide an additional therapeutic approach to complement irradiation and chemotherapy.

Adolescent↗

Efficacy of gadoteridol for magnetic resonance imaging of the brain and spine.

RATIONALE AND OBJECTIVES: The efficacy of gadoteridol for contrast enhancement of central nervous system pathology was assessed in a multicenter clinical trial involving 411 patients suspected of having intracranial or spinal pathology. METHODS: Magnetic resonance imaging was performed before and after intravenous administration of 0.10 mmol/kg gadoteridol. Two groups of images were interpreted by one of two neuroradiologists blinded to patient history. The results were analyzed separately. RESULTS: Patients with radiologic evidence of disease demonstrated enhancement of intracranial pathologic lesions in 44 of 63 (70%) and in 91 of 111 (82%) cases, respectively, whereas enhancement of spinal lesions was observed in 36 of 58 (62%) and in 65 of 78 (83%) cases, respectively. Subjectively, postcontrast scans provided more information than precontrast images in 37 of 63 (59%) and 84 of 111 (76%) intracranial cases, respectively, and in 25 of 58 (43%) and 55 of 78 (71%) spinal cases, respectively. Additional information included the subjective sense that there was improved visualization of pathology and definition of lesion borders. CONCLUSIONS: Subjective assessment of magnetic resonance scans suggest gadoteridol is an effective intravenous contrast agent for magnetic resonance imaging.

Adolescent↗

Induction of Arabidopsis defense genes by virulent and avirulent Pseudomonas syringae strains and by a cloned avirulence gene.

We developed a model system to study the signal transduction pathways leading to the activation of Arabidopsis thaliana genes involved in the defense against pathogen attack. Here we describe the identification and characterization of virulent and avirulent Pseudomonas syringae strains that elicit disease or resistance symptoms when infiltrated into Arabidopsis leaves. The virulent and avirulent strains were characterized by determining growth of the pathogen in Arabidopsis leaves and by measuring accumulation of mRNA corresponding to Arabidopsis phenylalanine ammonia-lyase (PAL), beta-1,3-glucanase (BG), and chalcone synthase (CHS) genes in infected leaves. The virulent strain, P. syringae pv maculicola ES4326, multiplied 10(5)-fold in Arabidopsis leaves and strongly elicited BG1, BG2, and BG3 mRNA accumulation but had only a modest effect on PAL mRNA accumulation. In contrast, the avirulent strain, P. syringae pv tomato MM1065, multiplied less than 10-fold in leaves and had only a minimal effect on BG1, BG2, and BG3 mRNA accumulation, but it induced PAL mRNA accumulation. No accumulation of CHS mRNA was found with either ES4326 or MM1065. We also describe the cloning of a putative avirulence (avr) gene from the avirulent strain MM1065 that caused the virulent strain ES4326 to grow less well in leaves and to strongly elicit PAL but not BG1 and BG3 mRNA accumulation. These results suggest that the Arabidopsis PAL and BG genes may be activated by distinct signal transduction pathways and show that differences in plant gene induction by virulent and avirulent strains can be attributed to a cloned presumptive avr gene.

Cloning, Molecular↗

Abnormal corpus callosum: a sensitive and specific indicator of multiple sclerosis.

The authors investigated whether identification of corpus callosal (CC) involvement might increase the specificity of magnetic resonance (MR) imaging in differentiating multiple sclerosis (MS) from other periventricular white matter diseases (PWDs). They prospectively evaluated 42 patients with MS and 127 control patients with other PWDs. Ninety-three percent of the MS patients demonstrated confluent and/or focal lesions involving the callosal-septal interface (CSI). These lesions characteristically involved the inferior aspect of the callosum and radiated from the ventricular surface into the overlying callosum. CSI lesions were optimally demonstrated on sagittal long repetition time (TR)/short echo time (TE) images and frequently (45% of cases) went undetected on axial images. Only 2.4% of the control patients had lesions of the CC. The authors conclude that midsagittal long TR/short TE images are highly sensitive and specific for MS and that callosal involvement in MS is more common than previously reported.

Adult↗

Phenylketonuria: MR imaging of the brain with clinical correlation.

Fifteen patients with biochemically documented phenylketonuria (PKU) were studied with use of magnetic resonance (MR) imaging with spin-echo T2-weighted pulse sequences. The resulting images demonstrated varying degrees of symmetric high signal intensity of the white matter within the posterior cerebral hemispheres. Involvement of the anterior hemispheres was seen only in cases with severe signal intensity changes. There was no involvement of the cerebral cortex, brain stem, or cerebellum. Moreover, no anatomic structural abnormalities were observed. Mild cortical atrophy was observed in eight of the 15 patients. There was no significant correlation between the patients' IQ scores and the level of MR signal intensity changes. Although MR imaging routinely shows relatively distinct abnormalities in patients with PKU, the clinical severity of the disease does not parallel its imaging severity.

Adolescent↗

Wallerian degeneration after cerebral infarction: evaluation with sequential MR imaging.

The dynamic signal intensity changes at magnetic resonance (MR) imaging in active and chronic wallerian degeneration in the corticospinal tract were evaluated. Forty-three patients with wallerian degeneration seen on MR images after cerebral infarction were studied. When possible, patients with acute stroke were examined with MR imaging prospectively at the onset of symptoms and then at weekly intervals for several months. Focal infarction without distal axonal degeneration is demonstrated for the 1st month following onset of clinical symptoms. At 4 weeks, a well-defined band of hypointense signal appears on T2-weighted images in the topographic distribution of the corticospinal tract. After 10-14 weeks, the signal becomes permanently hyperintense. Over several years, accompanying ipsilateral brain stem shrinkage occurs. The dark signal intensity observed on T2-weighted images between 4 and 14 weeks is believed to result primarily from transitory increased lipid-protein ratio.

Adult↗

Intracerebral arteriovenous malformations: evaluation with selective MR angiography and venography.

Magnetic resonance (MR) angiography and spin-echo methods were used to evaluate intracerebral arteriovenous malformations (AVMs) in 10 patients. Spin-echo images obtained with flow presaturation demonstrated the nidus of the AVM in all cases, but it was difficult to determine feeding vessels. These vessels were directly visualized with three-dimensional MR angiography; their presence could be indirectly determined by means of selective presaturation of individual vessels, which resulted in a marked decrease in signal within the portion of the AVM supplied by that vessel. Vascular supplies from the internal carotid artery and anterior, middle, or posterior cerebral arteries were detected in all cases, but in three large malformations it was not possible to demonstrate small feeding vessels. MR angiograms were also helpful for further defining the nidus. The combination of MR angiographic and spin-echo methods provides information useful for therapeutic planning not provided by either technique alone.

Adult↗

Wallerian degeneration: evaluation with MR imaging.

Twenty-three patients who underwent routine magnetic resonance (MR) imaging of the brain were found to have signal or structural abnormalities corresponding to white matter tracts. Images were evaluated for anatomic and MR signal characteristics of the involved tract, associated primary lesions, and, when possible, changes in MR signal and anatomic structures with time. Images from 20 patients demonstrated a thin band of abnormal signal contiguous with the primary lesion and conforming to the known anatomic pathway of a white matter tract. Cerebral infarction was the most common associated primary disorder (n = 17). Neoplasms (n = 2), demyelinating (n = 1) and posthemorrhagic (n = 2) conditions, and an idiopathic movement disorder (n = 1) were associated with white matter tract signal abnormalities that were indistinguishable from those seen with infarction. Signal abnormality corresponding to the corticospinal tract was the type most commonly seen. No change in signal characteristics was seen with time (six cases) or following contrast material administration (two cases). The authors conclude that MR imaging provides a sensitive method of evaluating wallerian degeneration in the living human brain.

Adult↗

Correlation of continuous-wave Doppler spectral flow analysis with gross pathology in carotid stenosis.

Preoperative continuous-wave Doppler spectral analysis was used to generate two parameters, peak frequency in the internal carotid artery (fmax) and the ratio of peak frequencies in the internal and common carotid arteries (carotid index). These were compared with direct measurement of residual lumen diameter in pathologic specimens obtained from carotid endarterectomy in 37 patients. Doppler shift frequency parameters were well correlated with residual lumen diameter when the latter was at least 1 mm. Residual lumens of less than or equal to 2 mm were found to have an fmax of greater than 7.5 kHz and a carotid index of greater than 3.8. If fmax was greater than 14 kHz or the carotid index was greater than 7, the residual lumen diameter was nearly always less than or equal to 1 mm. Thus, the severity of the stenosis correlated directly with Doppler shift frequencies. The length of stenoses did not affect the correlations.

Arteriosclerosis↗

Indications for treatment and classification of 132 carotid-cavernous fistulas.

Classification of carotid-cavernous fistulas (CCFs) into the four types described by Barrow allows the surgeon to choose the optimal therapy for each patient. Type A patients have fast flow fistulas that are manifest by a direct connection between the internal carotid arterial siphon and the cavernous sinus through a single tear in the arterial wall. The best therapy is obliteration of the connection by a detachable balloon. Ninety-two of 95 traumatic CCFs were treated in this fashion. Direct surgical exposure of the cervical or cavernous internal carotid artery (ICA) was necessary in the remaining 3 patients, who had undergone unsuccessful surgical trapping. Three ruptured cavernous aneurysms and 2 spontaneous CCFs also had Type A connections. Other carotid-cavernous fistulas are slow flow, spontaneous dural arteriovenous malformations (AVMs) that have been classified into B, C, and D types on the basis of arterial supply. Occlusion of the ICA is not a logical choice in the treatment of dural AVMs that occur in the elderly, are relatively benign, and are often bilateral. Type B are rare and are fed by meningeal branches of the ICA only. We have not seen this type of dural fistula in our series. Type C are supplied by feeders from the external carotid only and can almost always be obliterated successfully by embolizing the external carotid artery (ECA) branches. There are 4 Type C cases in this series of 37 spontaneous CCFs. All occurred in patients less than 30 years of age and were shunts between the middle meningeal artery and the cavernous sinus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗