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T Peterson

Publications and source records attributed to T Peterson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization of the regulatory elements of the maize P-rr gene by transient expression assays.

The maize P-rr gene conditions floral-specific flavonoid pigmentation, especially in the kernel pericarp and cob. We analyzed the P-rr promoter by transient expression assays, in which segments of the P-rr promoter were fused to the GUS reporter gene and introduced into maize cells by particle bombardment. A basal P-rr promoter fragment (-235 to +326) gave low, but significant, levels of GUS reporter gene expression. Interestingly, two widely spaced segments containing enhancer-like activity were found. When tested individually, both the proximal (-1252 to -236) and distal (-6110 to -4842) segments boosted expression of the basal P-rr promoter::GUS construct about five-fold. A 1.6 kb segment of the P-rr promoter (-1252 to +326) containing the proximal enhancer and the 5'-untranslated leader driving the GUS reporter gene showed preferential expression in BMS and embryogenic suspension cell cultures vs. endosperm-derived suspension cell cultures. These results demonstrate the application of transient assay techniques for the identification of regulatory elements responsible for floral-specific regulation of the complex P-rr gene promoter in maize.

DNA, Plant↗
PubMed1999

Voice and speech characteristics of persons with Parkinson's disease pre- and post-pallidotomy surgery: preliminary findings.

Pallidotomy surgery, lesioning the globus pallidus internal, has been performed to alleviate Parkinsonian symptoms and drug-induced dyskinesias. Improvements in limb motor function have been reported in recent years following pallidotomy surgery. The purpose of this preliminary study was to determine the effect of pallidotomy surgery on select voice and speech characteristics of 6 patients with Parkinson's disease. Acoustic measures were analyzed pre-pallidotomy surgery and again at 3 months following surgery. Preliminary findings indicated that all participants demonstrated positive changes in at least one acoustic measure; 2 of the participants consistently demonstrated positive changes in phonatory and articulatory measures, whereas 3 participants did not consistently demonstrate positive changes postsurgery. The results are discussed relative to the differential effects observed across participants.

Aged↗
PubMed1999

Genome rearrangements by nonlinear transposons in maize.

Transposable elements have long been considered as potential agents of large-scale genome reorganization by virtue of their ability to induce chromosomal rearrangements such as deletions, duplications, inversions, and reciprocal translocations. Previous researchers have shown that particular configurations of transposon termini can induce chromosome rearrangements at high frequencies. Here, we have analyzed chromosomal rearrangements derived from an unstable allele of the maize P1 (pericarp color) gene. The progenitor allele contains both a full-length Ac (Activator) transposable element and an Ac terminal fragment termed fAc (fractured Ac) inserted in the second intron of the P1-rr gene. Two rearranged alleles were derived from a classical maize ear twinned sector and were found to contain a large inverted duplication and a corresponding deficiency. The sequences at the junctions of the rearrangement breakpoints indicate that the duplication and deletion structures were produced by a single transposition event involving Ac and fAc termini located on sister chromatids. Because the transposition process we describe involves transposon ends located on different DNA molecules, it is termed nonlinear transposition (NLT). NLT can rapidly break and rejoin chromosomes and thus could have played an important role in generating structural heterogeneity during genome evolution.

Base Sequence↗
PubMed1999

Activated sulfonamides are cleaved by glutathione-S-transferases.

In preclinical pharmacokinetic studies and in in vitro rat, dog, and human primary hepatocyte incubations, the sulfonamide (-NH-SO(2)-) bond of a potent inhibitor of the HIV-1 protease containing the p-cyanopyridinyl moiety (PNU-109112), undergoes metabolic cleavage to form the corresponding amine metabolite (PNU-143070). Strikingly, a compound, PNU-140690, obtained by substituting the cyanopyridinyl group of PNU-109112 with a trifluoropyridinyl moiety, was stable under the same in vivo and in vitro conditions used for PNU-109112. The apparent "sulfonamidase activity" present in liver was localized to the cytosolic fraction and shown to be an enzyme-mediated reaction requiring reduced glutathione (GSH). The enzyme responsible was purified in a single step on a GSH immobilized gel and was identified as glutathione-S-transferase (GST) by sequence analysis of peptides obtained by tryptic digestion of the purified protein. Moreover, a mixture of GST isoenzymes purified from rat liver, and three recombinant human GST isoforms, A1-1, M1-1, and P1-1, were active toward PNU-109112 sulfonamide cleavage; the three isoforms exhibited differential rates of PNU-109112 cleavage, demonstrating isoenzyme selectivity.

Amino Acid Sequence↗
PubMed1999

Mechanism, structure-activity studies, and potential applications of glutathione S-transferase-catalyzed cleavage of sulfonamides.

The mechanism of sulfonamide cleavage of PNU-109112, a potent HIV-1 protease inhibitor, by glutathione-S-transferase (GST) was investigated in the presence of reduced GSH. GST-catalyzed sulfonamide cleavage takes place via the nucleophilic attack of GSH on the pyridine moiety of the substrate with formation of the GS-para-CN-pyridinyl conjugate, the corresponding amine, and sulfur dioxide. Structure activity studies with a variety of sulfonamides indicate that an electrophilic center alpha to the sulfonyl group is required for cleavage. Substituents that withdraw electron density from the carbon atom alpha- to the sulfonyl group facilitate nucleophilic attack by the GS(-) thiolate bound to GST. The rate of sulfonamide cleavage is markedly affected by the nature of the electrophilic group; replacement of para-CN by para-CF(3) on the pyridine ring of PNU-109112 confers stability against sulfonamide cleavage. On the other hand, stability of sulfonamides is less dependent on the nature of the amine moiety. These principles can be applied to the synthesis of sulfonamides, labile toward cellular GST, that may serve as prodrugs for release of bioactive amines. Tumors are particularly attractive targets for these sulfonamide prodrugs as GST expression is significantly up-regulated in many cancer cells. Another potential application could be in organic synthesis, where protection of amines as the corresponding activated sulfonamides can be reversed by GST/GSH under mild conditions.

Caco-2 Cells↗
PubMed1998

Bacillus licheniformis MC14 alkaline phosphatase I gene with an extended COOH-terminus.

Bacterial alkaline phosphatases (APases), except those isolated from Bacillus licheniformis, are approximately 45-kDa proteins while eucaryotic alkaline phosphatases are 60 kDa. To answer the question of whether the apparent 60-kDa alkaline phosphatase from Bacillus licheniformis accurately reflected the size of the protein, the entire gene was analyzed. DNA sequence analysis of the alkaline phosphatase I (APaseI) gene of B. licheniformis MC14 indicated that the gene could code for a 60-kDa protein of 553 amino acids. The deduced protein sequence of APaseI showed about 32% identity to those of B. subtilis APase III and IV and had apparent sequence homologies in the core structure and active sites that are conserved among APases of various sources. The extra carboxy-terminal sequence of APaseI, which made the enzyme bigger than other procaryotic APases, was not homologous to those of eucaryotic APases. The amino acid composition of APaseI was most similar to that of salt-dependent APase among the isozymes of B. licheniformis MC14. Another open reading frame of 261 amino acids was present 142 nucleotide upstream of the APaseI gene and its predicted amino acid sequence showed 68% identity to that of glucose dehydrogenase of B. megaterium.

Alkaline Phosphatase↗
PubMed1998

A maize Myb homolog is encoded by a multicopy gene complex.

The maize P gene encodes a Myb-homologous transcriptional regulator of flavonoid pigmentation in floral organs, and different P gene alleles condition precise tissue- and organ-specific pigmentation patterns. To determine the molecular basis for allele-specific expression patterns, we have isolated and compared two natural alleles of the P gene which differ in expression, structure and copy number. The P-rr allele is associated with pigmentation of most floral tissues and contains a single copy of the P gene. In contrast, the P-wr allele restricts pigmentation to a subset of floral tissues, and is composed of six gene copies arranged in a tandem head-to-tail array. Each of the six repeats contains a single P gene, including regulatory and coding sequences. Despite the six-fold tandem repetition of P-wr gene copies, P-wr mRNA levels in kernel pericarp are much reduced compared to mRNA levels from the single-copy P-rr gene. Moreover, the P-wr multicopy complex is hypermethylated relative to P-rr. Thus, maize P gene alleles may represent a natural system for studying the effects of methylation and gene copy number on tissue-specific gene expression. We discuss the possibility that somatic pairing of repeated gene copies may be involved in regulating gene expression.

Alleles↗
PubMed1997

Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice.

OBJECTIVE: To define the true risk of hydroxychloroquine (HCQ) retinal toxicity by studying the largest single group yet evaluated. METHODS: Retrospective chart review of all patients in the Kaiser Permanente Medical Care Program, Southern California Region, who had HCQ prescriptions filled from 1991 through 1993 (1,556 patients in 11 medical centers). Of 1,207 charts of patients who took HCQ and had documented ophthalmologic examinations, initial screening identified 21 charts (1.7%) that indicated possible HCQ toxicity. RESULTS: We identified 1 patient with definite toxicity (1 of 1,207; 0.08%) and 5 other patients with indeterminate but probable toxicity (5 of 1,207; 0.4%). The incidence of definite HCQ retinal toxicity in patients treated with HCQ at <6.5 mg/kg/day was 0. CONCLUSION: In HCQ-treated patients whose renal function is normal, routine ophthalmic screening is not indicated if the daily dosage is <6.5 mg/kg. In patients whose daily dosage is >6.5 mg/kg or who have taken HCQ continuously for > 10 years, annual screening may be appropriate.

Adult↗
PubMed1997

Simultaneous arterial and urinary bladder pressure recordings in multiple system atrophy and in spinal disorders with detrusor hyperreflexia.

Simultaneous arterial and urinary bladder pressure measurements were recorded during bladder filling in 21 patients with urinary bladder symptoms; seven patients had autonomic failure due to multiple system atrophy (MSA), seven had spinal cord disease of different aetiology with detrusor hyperreflexia (DH) and seven had no neurological abnormalities. A significant increase in average systolic blood pressure (BP) was recorded on bladder filling in the neurologically intact patients (from 110 to 137 mmHg) and in the patients with spinal cord disease and DH (from 109 to 129 mmHg). In those with MSA, the BP rose in four and fell in three patients. The vesicopressor response during cold receptor-mediated DH was not significantly higher when compared with room-temperature saline and when compared with the BP response during bladder filling in the neurologically intact patients. Finally, intravesical lignocaine retained in the bladder for 15 min did not influence the BP response to cold receptor stimulation in patients with spinal cord disease and DH. These findings and their pathophysiological and clinical implications are discussed.

Adult↗
PubMed1997

Capnography and ventilatory assessment during ambulatory dentoalveolar surgery.

PURPOSE: The purpose of this study was to determine whether capnography is a more sensitive monitor than auscultation of breath sounds in detecting ventilatory changes consistent with hypoventilation, obstruction, or apnea and in detecting ventilatory changes that can be associated with oxygen desaturation. PATIENTS AND METHODS: Fifty-five patients received intravenous agents and supplemental oxygen to achieve a state of deep sedation or general anesthesia for removal of impacted third molars. The surgeon/anesthetist monitored respiratory status using a pretracheal stethoscope and direct observation. A blinded observer with no access to the patient or anesthetist monitored respiratory status using capnography. A second observer monitored all respiratory parameters to allow for correlation between clinical and electronic monitors. RESULTS: Ventilatory status was continuously represented by capnogaphy. The Pearson correlation coefficient showed a positive correlation between increased end-tidal CO2 (PETCO2) and decreased oxygen saturation that became stronger with greater positive changes in PETCO2. An additive relationship was found between PETCO2 and respiratory rate (RR), with increased PETCO2 and decreased RR contributing to decreased oxygen saturation. CONCLUSION: Patients with nasal ventilatory exchange maintain this exchange throughout the anesthesia so that sampling of nasal PETCO2 is an effective way to monitor ventilatory status. Respiratory depression or obstructive ventilatory changes detected by capnography showed a high sensitivity and low positive predictive value in detecting oxygen desaturation. The current technology does not show a clinically satisfactory correlation between PETCO2 and oxygen saturation. However, a combined increase in PETCO2 and decrease in RR suggested a trend of decreasing oxygen saturation.

Adolescent↗
PubMed1997

Common bile duct stones in acute biliary pancreatitis: an endoscopic study.

The knowledge of the natural history of common bile duct stones in biliary pancreatitis may be helpful in the debate concerning the timing of endoscopic sphincterotomy in relation to surgery. The endoscopic cholangiographies of 211 patients with biliary pancreatitis were analyzed. The presence of bile duct stones was recorded, as well as the time interval between admission and endoscopic retrograde cholangiopancreatography (ERCP). The predicted severity of pancreatitis was determined by the modified Glasgow criteria. The overall incidence of bile duct stones was 28.9%. This incidence was 43.8% during the first 2 days and decreased to < 20% after 1 week. There was no correlation between the severity of disease and the presence of bile duct stones. The performance of an ERCP 1 week after the admission for biliary pancreatitis will avoid a substantial number of unnecessary endoscopic sphincterotomies. Prediction of the severity of disease does not alter the yield of bile duct stones.

Acute Disease↗
PubMed1997

Screening for concomitant diseases in peripheral vascular patients. Results of a systematic approach.

BACKGROUND: Patients considered for arterial surgery, have been shown to have a high incidence of coexistent cardiac, vascular and other diseases, affecting operative risk and survival. We developed a systematic workup strategy for detecting these coexistent diseases in our vascular surgical patients, mainly based on non-invasive diagnostic techniques. METHODS: We evaluated 200 consecutive patients, admitted to the department of vascular surgery in an academic teaching hospital, in order to establish the total incidence of relevant concomitant disorders, the extent to which this screening yielded previously unknown diagnostic information, and the impact on short-term (one year) survival. RESULTS: Coronary artery disease was present in 46% of the patients; 22% had active ischaemia, newly diagnosed in 5.5%. Impaired cardiac function was found in 37%: severely impaired in 12%, newly diagnosed in 27%. Carotid artery disease was present in 32%: critical stenoses were found in 9%; new diagnoses in 29.9%. Aortic aneurysms were present in 7%, newly diagnosed in 5%. Severe renal artery stenosis was present in 5%, newly diagnosed in 3.5%. Sixteen % of the patients had chronic obstructive pulmonary disease, newly diagnosed in 3.5%, and 4.5% had unexpected disorders, which were all new diagnoses. Overall, new diagnoses were reached in 64.5% of the population, affecting therapeutic strategy immediately in 21% of the patients. The presence of coronary artery disease and of cardiac failure were clearly related to one year survival. CONCLUSIONS: We conclude that a systematic screening strategy, mainly based on noninvasive techniques, can detect the presence of concomitant diseases in the vascular surgical patient. Most important seem the newly diagnosed diseases altering surgical management in one out of every five patients; they also have important implications for patient prognosis.

Aged↗
PubMed1996

Novenamines as inhibitors of two independent enzymes during DNA replication in a toluenized Escherichia coli cell system.

The amphiphilic novenamines described in this report have been shown previously to be specific inhibitors of human immunodeficiency virus type 1 reverse transcriptase-associated ribonuclease, which they inhibit when they are in the micellar state but not when they are monomeric. These compounds also inhibit the bacterial enzyme DNA gyrase, which is essential for DNA replication. Hence, the present studies were initiated to determine whether the molecular species inhibiting the gyrase reaction was the monomeric or the micellar form. For this purpose, the rate of DNA replication was measured in a toluenized Escherichia coli cell system in the presence of increasing concentrations of novenamines. The resulting concentration-response curves proved anomalous, suggesting the involvement of micelles or some other, noncovalently aggregated forms of the inhibitors. The results were analyzed in terms of a variety of kinetic schemes and were found to be most consistent with the model where novenamines inhibit replicative DNA synthesis predominantly as cooperative dimers and, to a lesser extent, as monomers, but not as highly aggregated micelles. Based on this analysis and the knowledge that novobiocin and all novenamine-containing analogs are powerful gyrase inhibitors, we conclude that the target of the cooperative, dimeric inhibition is the gyrase, whereas the monomers of the novenamines inhibit another enzyme species involved in the bacterial DNA replication process.

DNA↗
PubMed1996

The amphiphilic properties of novenamines determine their activity as inhibitors of HIV-1 RNase H.

Few inhibitors of the RNase H function associated with the HIV-1 reverse transcriptase have been discovered to date. We observed that three novenamines, U-34445, U-35122, and U-35401, are specific inhibitors of the HIV-1 RT RNase H function. All three compounds are strong amphiphiles and contain one ionizable group. Hence, a priori, in aqueous solutions the inhibitors might exist in at least four different physical states, namely protonated monomers, ionized monomers, protonated micelles, and ionized micelles. The three inhibitors all yielded anomalous dose-response curves, indicating that the four molecular species have different inhibitory potentials. In order to identify the inhibitory species, the amphiphilic properties of these compounds were studied. It was established that in alkaline solutions, around pH 8, all compounds are ionized and form micelles at concentrations above their CMC. Both the protonated and the ionized forms of these molecules form stable insoluble monomolecular layers at the air/water interface. The anomalies of the dose-response curves can be resolved by taking into account the fact that, in solution, the relative proportion of these molecules in each physical state depends on the pH and on their analytical concentration. Thus interpreted, the results indicate that RNase H is inhibited only by the ionized micellar form of these compounds and not by their monomeric form. Around their pKa (approximately pH 5), the three compounds reproducibly form uniformly sized, self-emulsified colloidal particles that may be used as an efficient drug delivery system.

Chemical Phenomena↗
PubMed1996

Positioning jig for implant abutments: procedures and clinical applications.

A custom-milled abutment may be positioned in six different orientations on a hexed implant. When more than one implant abutment is to be placed, the number of possible orientations increases and makes this step time consuming. It is imperative that the abutment be held in a fixed position while the abutment screw is tightened. Occasionally the master working cast is not accurate and a procedure to correct the cast without making a new impression is required. This article describes a procedure for making and using a positioning jig to alleviate these problems.

Dental Abutments↗