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Biomedical subjects

W D Wilson

Publications and source records attributed to W D Wilson.

At least 235 records · Page 13Linked to original sources
PubMed1972

Photolysis accompanying peptide absorption in proteins. Electrophoresis and optical rotary dispersion studies.

Exposure of proteins and polypeptides to ultraviolet radiation below 240 nm produces peptide cleavage which may or may not be accompanied by observable changes in conformation and optical rotary dispersion (ORD) properties, depending on the stability of the secondary and tertiary structure of the macromolecule under the experimental conditions. Helical and coiled forms of poly-L-glutamic acid undergo degradation at similar rates but only the helical form shows a significant change in rotatory properties. The helical form of poly-L-lysine, but neither the coiled nor beta forms, shows a change in [alpha](233) on irradiation at 233 nm. beta-Lactoglobulin shows essentially no change in [alpha](233) on irradiation in either dilute salt solution or 4 M urea at room temperature; however, in 4 M urea at 56 degrees C a large change occurs. A model is developed which shows that studies of the effect of radiation on ORD properties may be useful in providing information on possible intermediate steps in protein denaturation. The method is illustrated with results on bovine plasma albumin. A quantum yield, 4.3 x 10(-3) moles/einstein, was obtained for peptide cleavage in this protein at 225 nm. These studies, based on gel electrophoresis, also showed that the fragments produced are essentially random, suggesting that transfer of energy from aromatic residues is not an important contributor to the peptide photolysis. Possible errors which could arise in ORD and other studies involving intense ultraviolet radiation are considered.

Animals↗
PubMedDate not supplied

Design and analysis of RNA structure-specific agents as potential antivirals.

A number of pathogenic RNA viruses, such as HIV-1, have extensive folded RNA conformations with imperfect A-form duplexes that are essential for virus function, and could serve as targets for structure-specific antiviral drugs. A method for the discovery of such drugs involves evaluation of the interactions with RNA of a wide variety of compounds that are known to bind to nucleic acids by different mechanisms. This approach has been initiated by using corresponding sequence RNA and DNA polymers as initial test systems for analysis of RNA binding strength and selectivity. Compounds that bind exclusively in the minor groove in AT sequences of DNA do not have significant interactions with RNA. Polycations, however, can show significant RNA affinity and binding selectivity, probably through complex formation in the RNA major groove. Some intercalators and a group of diphenylfuran cations have strong interactions with RNA that are very dependent on compound structure. RNA hairpin model systems for the RRE binding site of HIV-1 Rev protein were constructed for more detailed investigations. The diphenylfuran cations bind strongly to RRE and selectively inhibit Rev binding. CD, NMR, and fluorescence binding studies indicate that the active compounds bind in the internal loop region of RRE (with binding constants > 10(7)M-1), and cause a conformational change in the RNA. None of the standard nucleic acid binding modes appears to fit the results for complexes of the active compounds with RRE, and it is proposed that the diphenylfuran system threads through the internal loop region of RRE. Such a model allows contacts of the furan cationic substituents with both grooves of RRE in addition to the intercalation interactions with the bases.

Antiviral Agents↗
PubMedDate not supplied

Binding of meso-tetrakis(N-methylpyridiniumyl)porphyrin isomers to DNA: quantitative comparison of the influence of charge distribution and copper(II) derivatization.

Factors influencing the binding of tetracationic porphyrin derivatives to DNA have been comprehensively evaluated by equilibrium dialysis, stopped-flow kinetics, etc., for mesotetrakis (4-N-methylpyridiniumyl)porphyrin [TMpyP (4)]. Technical difficulties have previously precluded a comprehensive study of metalloporphyrins. Since electrostatic interactions with the DNA and metal derivatization of the porphyrins have important consequences, we have investigated in greater detail two isomers of TMpyP (4) (meso-tetrakis(3-N-methylpyridiniumyl)porphyrin, [TMpyP (3)] and meso-tetrakis(2-N-methylpyridiniumyl)porphyrin [TMpyP (2)]) in which the position of the charged centers has been varied. A comprehensive study of the Cu(II) derivatives, e.g., CuTMpyP (4), was possible since the difficulties encountered previously with Ni(II) compounds were not a problem with Cu(II) porphyrins [J. A. Strickland, L. G. Marzilli, M. K. Gay, and W. D. Wilson (1988) Biochemistry 27, 8870-8878]. At 25 degrees C, the apparent equilibrium constants [Kobs] decreased with increasing [Na+] for all porphyrins. The Kobs values were comparable for TMpyP (4) and TMpyP (3) binding to either polyd(G-C).polyd(G-C) [poly[d(G-C)2]] or poly[d(A-T)].poly[d(A-T)] [poly[d(A-T)2]]. For the copper(II) porphyrins, the Kobs values were about fivefold greater. The Kobs value for CuTMpyP (2) binding to poly[d(G-C)2] was too small to measure under typical salt conditions; however, Kobs for binding to poly[d(A-T)2] was about two orders of magnitude smaller than those found for CuTMpyP (4) or CuTMpyP (3). Application of the condensation theory for polyelectrolytes suggests about three charge interactions when CuTMpyP (4), CuTMpyP (3), and TMpyP (3) bind to poly[d(G-C)2] or poly[d(A-T)2], a result comparable to that reported for TMpyP (4). At 20 degrees C and 0.115 M [Na+], incorporation of copper decreased the rates of dissociation from poly[d(A-T)2] by a 100-fold compared to those reported for TMpyP (4) but had little effect on the rates of dissociation from poly[d(G-C)2]. Also, movement of the H3CN+ group from the fourth to the third position of the pyridinium ring enhanced the rates of dissociation from poly[d(A-T)2] but decreased the rates of dissociation from poly[d(G-C)2]. From polyelectrolyte theory, the [Na+] dependence of the dissociation rates from poly[d(G-C)2] is consistent with intercalative binding, while that for poly[d(A-T)2] is consistent with an outside binding model. For calf thymus [CT] DNA at 20 degrees C, a greater decrease in the AT than in the GC imino 1H-nmr signal was observed upon addition of CuTMpyP (2), suggesting selective outside binding to the AT regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗
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Synthesis and anti-Pneumocystis carinii pneumonia activity of novel dicationic dibenzothiophenes and orally active prodrugs.

Dicationic carbazoles have been found to be highly active against a rat model of Pneumocystis carinii pneumonia (PCP). Unfortunately, amidoxime derivatives, designed as prodrugs, were inactive against PCP even though the corresponding amidines were highly active. In the present work, a series of 2,8- and 3,7-bis cationic dibenzothiophenes was synthesized and assayed for anti-PCP activity. Three of the compounds proved to be more potent and less toxic than a standard anti-PCP drug (pentamidine) when given intravenously. Unlike the carbazoles, a dibenzothiophene amidoxime prodrug given orally reduced the parasite load by more than 99%. While no quantitative correlation was seen between anti-PCP activity and DNA binding, a strong level of DNA binding was found to be necessary for antimicrobial activity.

Animals↗
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Molecular recognition of quadruplex DNA by quinacridine derivatives.

The interaction of monomeric and dimeric quinacridines with quadruplex DNA has been investigated using a variety of biophysical methods. Both series of compounds were shown to exhibit a high affinity for the G4 conformation with two equivalent binding sites. As shown from the SPR and dialysis experiments the macrocyclic dimer appears more selective than its monomeric counterpart.

Base Sequence↗
PubMedDate not supplied

Bronchointerstitial pneumonia and respiratory distress in young horses: clinical, clinicopathologic, radiographic, and pathological findings in 23 cases (1984-1989).

Twenty-three foals, between 1 and 7 months old, with signs of acute respiratory distress, were examined at the Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, between 1984 and 1989. Characteristic features included sudden onset of severe respiratory distress and tachypnea, cyanosis unresponsive to nasal oxygen, pyrexia, hypoxemia, hypercapneic respiratory acidosis, poor response to treatment, and histopathologic lesions of bronchiolitis and bronchointerstitial pneumonia. Seven of the 23 foals were normal before the onset of respiratory distress, 3 foals were found dead, and 13 foals were being treated for respiratory tract infections at the time of presentation. Laboratory data obtained for 13 horses showed increased plasma fibrinogen concentration (630.7 +/- 193 mg/dL), leukocytosis (18,607 +/- 7,784/microL), and neutrophilia (13,737 +/- 8,211/microL). Thoracic radiographs showed a diffuse increase in interstitial and bronchointerstitial pulmonary opacity and, in 5 foals, an alveolar pulmonary pattern of increased density was also seen. In 3 foals heavy interstitial infiltration proceeded to a coalescing nodular radiographic appearance. Microbiological culture of tracheobronchial aspirates (TBA) from 9 foals yielded bacterial growth, but no one bacterial species was consistently isolated. Microbiological culture of postmortem specimens of the lung from 6 foals yielded growth of bacteria that included Escherichia coli, Enterobacter spp., Proteus mirabilis, Klebsiella pneumoniae, Rhodococcus equi, or beta-hemolytic Streptococcus spp. Tracheobronchial aspirates from 4 foals and lung samples collected from a further 4 foals at necropsy yielded no bacterial growth. Cultures were not taken from two foals premortem or postmortem. Virologic examination of TBA, lung tissue, or pooled organ tissue from 12 foals was negative. Viral culture of TBA from 1 foal showed cytopathic effects and positive immunofluorescence for equine herpes virus type II (EHV-II). In addition to the 3 foals that were found dead, 11 foals died or were euthanatized. Pathologic lesions were limited to the lungs in 50% of the foals; the remainder also had bowel lesions suggestive of hypoxic injury. The predominant histopathologic pulmonary lesions included bronchiolitis, bronchiolar and alveolar epithelial hyperplasia, and necrosis. Many bronchioles were filled with mucoid and fibrinocellular exudate. The peribronchiolar interstitium and adjacent alveolar spaces were also infiltrated with inflammatory cells and contained proteinaceous edema fluid. Type II cell hyperplasia and hyaline membrane formation were observed in the majority of foals and in 2 foals alveolar multinucleate giant cells were also present.(ABSTRACT TRUNCATED AT 400 WORDS)

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Acute hemoperitoneum in horses: a review of 19 cases (1992-2003).

The medical records of 19 horses with acute hemoperitoneum were reviewed. The causes for the hemoperitoneum were idiopathic (8 horses), splenic hematoma with capsular tear (7), bleeding from the reproductive tract (3), multicentric hemangiosarcoma (1), and systemic amyloidosis (1). The affected horses were between 4 and 32 years of age (median 11.5 years). The most consistent findings on initial examination were depression, tachycardia, tachypnea, pale mucous membranes, prolonged capillary refill time, colic, and abdominal discomfort. Less common clinical signs included abdominal distention, profuse sweating, ataxia, and broad ligament mass palpated on rectal examination. Clinicopathologic abnormalities commonly detected were anemia, neutrophilia, lymphopenia, thrombocytopenia, hypoproteinemia, hypocalcemia, azotemia, increased creatinine kinase, and sorbitol dehydrogenase activity. Hemoperitoneum was diagnosed on the basis of abdominocentesis, transabdominal ultrasonography, and postmortem examination. Sixteen horses were treated, and 3 horses were euthanized at owners' request because of severe clinical signs. The treatment consisted of the administration of intravenous fluids, plasma or blood transfusion, nonsteroidal drugs, antimicrobial drugs, and antifibrinolytic and procoagulant agents. Rapid clinical deterioration was observed in 2 horses, necessitating euthanasia. The remaining 14 horses survived the abdominal bleeding (survival rate 74%) and were discharged 3-15 days (median 7.0 days) after presentation. Postmortem examination of the 6 nonsurvivors showed massive abdominal hemorrhage from splenic hematoma with capsular tear (2 horses), multicentric hemangiosarcoma with liver rupture (1), systemic amyloidosis with splenic hematoma and capsular tear (1), and bilateral ruptured ovarian hematomas (1). In one horse, no origin of the bleeding could be determined during postmortem examination.

Animals↗
PubMedDate not supplied

Intestinal neoplasia in horses.

BACKGROUND: Intestinal neoplasia of horses is inadequately described. HYPOTHESIS: Intestinal neoplasia of horses has characteristic clinicopathologic features. ANIMALS: Thirty-four horses with intestinal neoplasia. METHODS: Retrospective study. RESULTS: Anamnesis, clinical signs, clinicopathologic and pathologic findings in 34 adult horses diagnosed histologically with intestinal neoplasia were reviewed. The horses ranged in age from 2 to 30 years (mean 16.6 years at presentation). The Arabian breed was most represented and there was no sex predisposition. The most common presenting complaints were weight loss, colic, anorexia, and fever. The most consistent clinical signs were poor body condition, tachycardia, tachypnea, fever, and diarrhea. Useful diagnostic tools included rectal examination, routine blood analyses, abdominocentesis, ultrasonographic examination, rectal biopsy, and exploratory laparotomy. Alimentary lymphoma was the most common intestinal neoplasia identified, followed by adenocarcinoma and smooth muscle tumors. The small intestine was the most common segment of intestine affected for all neoplasms. Intestinal neoplasia was diagnosed antemortem in 13 of 34 (38%) horses. The median time from onset of clinical signs to death or euthanasia was 1.9 months. The discharge rate was 15%. Although the longest survival was observed in horses with jejunal adenocarcinoma, all horses were eventually euthanized because of intestinal neoplasia. CONCLUSIONS: Arabian horses were 4.5 times more likely to have intestinal neoplasia diagnosed than were other breeds.

Age Factors↗