Biomedical subjects

P W Wright

Publications and source records attributed to P W Wright.

At least 19 recordsLinked to original sources

PubMed1999

Structure, properties, and tissue localization of apoplastic alpha-glucosidase in crucifers.

Apoplastic alpha-glucosidases occur widely in plants but their function is unknown because appropriate substrates in the apoplast have not been identified. Arabidopsis contains at least three alpha-glucosidase genes; Aglu-1 and Aglu-3 are sequenced and Aglu-2 is known from six expressed sequence tags. Antibodies raised to a portion of Aglu-1 expressed in Escherichia coli recognize two proteins of 96 and 81 kD, respectively, in vegetative tissues of Arabidopsis, broccoli (Brassica oleracea L.), and mustard (Brassica napus L.). The acidic alpha-glucosidase activity from broccoli flower buds was purified using concanavalin A and ion-exchange chromatography. Two active fractions were resolved and both contained a 96-kD immunoreactive polypeptide. The N-terminal sequence from the 96-kD broccoli alpha-glucosidase indicated that it corresponds to the Arabidopsis Aglu-2 gene and that approximately 15 kD of the predicted N terminus was cleaved. The 81-kD protein was more abundant than the 96-kD protein, but it was not active with 4-methylumbelliferyl-alpha-D-glucopyranoside as the substrate and it did not bind to concanavalin A. In situ activity staining using 5-bromo-4-chloro-3-indolyl-alpha-D-glucopyranoside revealed that the acidic alpha-glucosidase activity is predominantly located in the outer cortex of broccoli stems and in vascular tissue, especially in leaf traces.

Amino Acid Sequence↗

PubMed1998

Inhibition of Fas (CD95) expression and Fas-mediated apoptosis by oncogenic Ras.

The ras oncogene plays an important role in the multistep progression to cancer by activation of signal transduction pathways that contribute to aberrant growth regulation. Although many of these effects are cell autonomous, the ras oncogene also regulates the expression of genes that alter host/tumor interactions. We now extend the mechanisms through which ras promotes tumor survival by demonstrating that oncogenic Ras inhibits expression of the fas gene and renders Ras-transformed cells resistant to Fas-induced apoptosis. A panel of Ras-transformed clones exhibited a marked inhibition in fas mRNA and Fas cell surface expression as compared with untransformed parental cell lines. Fas expression was induced by culture in the presence of IFN-gamma + tumor necrosis factor alpha; however, the maximal level attained in Ras transformants was approximately 10-fold below the level of untransformed cells. Whereas untransformed cells were sensitive to apoptotic death induced by cross-linking surface Fas (especially after cytokine treatment), Ras-transformed cells were very resistant to Fas-induced death even under the most stringent assay conditions. To demonstrate that this resistance was mediated by oncogenic Ras and not secondary genetic events, pools of Ras-transformed cells were generated using a highly efficient retroviral transduction technique. Transformed pools were assayed 6 days after infection and demonstrated a marked decrease in fas gene expression and Fas-mediated apoptosis. Oncogenic Ras did not promote general resistance to apoptosis, because ectopic expression of a fas cDNA in Ras-transformed cells restored sensitivity to Fas-induced apoptosis. These data indicate that oncogenic Ras inhibits basal levels of expression of the fas gene, and although cytokine signal transduction pathways are functional in these cells, the level of surface Fas expression remains below the threshold required for induction of apoptosis. These data identify a mechanism by which Ras-transformed cells may escape from host-mediated immune destruction.

3T3 Cells↗

PubMed1998

T cell- and NK cell-independent inhibition of hepatic metastases by systemic administration of an IL-12-expressing recombinant adenovirus.

IL-12 is a potent immunoregulatory cytokine that has been shown to mediate tumor regression in a variety of tumor models. We describe the construction of AdCMV-IL-12, a recombinant adenovirus that encodes both subunits of IL-12 under transcriptional control of the CMV promoter. This recombinant virus efficiently infects a wide variety of cell types leading to the production of high levels of biologically active IL-12. Because the liver is a primary site of infection after i.v.-administered adenovirus, we tested the therapeutic efficacy of this virus in a murine hepatic metastasis tumor model. Systemic administration of AdCMV-IL-12 dramatically inhibited the formation of 3-day Renca hepatic metastases (mean of 16 metastases per liver) compared with the control virus AdCMV-betagal (mean of 209) or vehicle alone (mean of 272). Histologic analysis indicated that metastatic growth inhibition was accompanied by a dramatic perivascular infiltrate consisting of T cells, macrophages, and neutrophils. Therapeutic efficacy was not diminished in animals depleted of CD4+ or CD8+ T cells, or in SCID mice, even after NK cell ablation. In the latter case, a hepatic perivascular infiltrate composed of macrophages and neutrophils was observed after AdCMV-IL-12-treatment, while numerous activated Kupffer cells were noted in the hepatic parenchyma. Analysis of therapy-induced changes in hepatic gene expression demonstrated increased levels of IP-10 and Mig RNAs, but no increase in iNOS, Fas, or FasL RNA levels was observed. Our data suggest a model of metastatic growth inhibition mediated by nonlymphocyte effector cells including macrophages and neutrophils and that may involve anti-angiogenic chemokines.

Adenocarcinoma↗

PubMed1998

Sensitivity of fluorochrome microscopy for detection of Mycobacterium tuberculosis versus nontuberculous mycobacteria.

The results for 6,532 consecutive mycobacterial respiratory specimens collected from 1,040 patients from 1993 to 1995 in a Texas hospital were studied to determine the sensitivity of fluorescence microscopy for detection of Mycobacterium tuberculosis and nontuberculous mycobacteria (NTM). Smears were positive for acid-fast bacilli (AFB) in 63% (677 of 1,082) of specimens growing M. tuberculosis and 56% (638 of 1,148) of specimens growing the four most common species of NTM. Smear positivity by species was 58% (446 of 776) for M. avium complex, 51% (154 of 300) for rapidly growing mycobacteria (98% were M. abscessus), 78% (29 of 37) for M. kansasii, and 26% (9 of 35) for M. gordonae. Definite or probable disease by clinical criteria was present in 79% of patients with M. avium complex, 93% of patients with rapidly growing mycobacteria, 100% of patients with M. kansasii, and 0% of patients with M. gordonae. Patients with M. avium complex had a low incidence of AIDS (7%), and approximately 50% of non-AIDS patients had upper-lobe cavitary disease and 50% had nodular bronchiectasis. Only 23 of 6,532 (0.35%) of AFB smears were positive with a negative culture excluding patients on therapy for established mycobacterial disease. These studies suggest that NTM are as likely as M. tuberculosis to be detected by fluorescent microscopy in specimens from patients from areas endemic for NTM lung disease and at low risk for AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Should balloon angioplasty and stents have any role in operative intervention for lower extremity ischemia?

Balloon angioplasty has been combined with open vascular surgery to treat lower extremity ischemia due to multilevel occlusive disease. The purposes of this study were: (1) to compare staged and simultaneous approaches to determine the optimal method for combining endovascular and open techniques and; (2) to assess the role of stents in intraoperative balloon angioplasty. Among 274 patients undergoing lower extremity revascularization over 30 months, 38 (13.9%) required a combination of endovascular and open techniques; 17 were staged (endovascular followed at an interval by distal open surgery) and 21 were simultaneous (intraoperative balloon angioplasty with or without stent placement at the time of open surgery). Groups were similar with respect to demographics, lesions treated with endovascular intervention, incidence and location of stent placement, and results of surgery. Additional operating time required for intraoperative endovascular intervention was 41.0 +/- 30.7 min., fluoroscopic time was 3.9 +/- 2.4 min. and contrast administered was 58.8 +/- 28.1 ml. There was no perioperative mortality. Length of stay was longer in the staged than in the simultaneous group (p < 0.01). Cumulative combined primary patency at 1 year by life-table methods was 82 +/- 10% in the staged group and 83 +/- 9% in the simultaneous group (p = 0.79). Mean follow-up was 13 +/- 6 months. There is a role for balloon angioplasty and stent placement in operative revascularization of ischemic limbs in selected patients: patency was similar to that produced with the staged approach while the length of stay was shorter. Intraoperative balloon angioplasty is safe and effective and stents permit a measure of control in assuring an optimal intraoperative postangioplasty result.

Aged↗

PubMed1995

Selection of skin test antigens to evaluate PPD anergy.

BACKGROUND: A purified protein derivative (PPD) tuberculin skin test may be nonreactive because of cutaneous anergy, technical problems with the test, or absence of tuberculosis infection. This study investigated the sensitivity and specificity of five test agents in measuring cutaneous anergy when the PPD test is nonreactive. Agents evaluated include antigens for Candida, mumps, histoplasmin, tetanus, and Trichophyton. METHODS: Delayed-type hypersensitivity skin test records were analyzed in 1113 patients admitted to the University of Texas Health Center at Tyler from December 1988 through June 1993. These patients were admitted with initial diagnoses of diseases other than active tuberculosis or human immunodeficiency virus infection. RESULTS: Patients with a negative PPD test reacted most often to the control skin test Candida (63.5%), followed by mumps (52.2%), histoplasmosis (37.2%), tetanus (35.7%), and Trichophyton (6.1%). Analysis of these data indicates that the use of more than three of the four most commonly reactive control tests (Candida, mumps, and histoplasmin or tetanus) yielded minimal additional precision in the determination of skin test anergy compared with using all five control skin tests. This finding remained constant whether the PPD was considered negative at < 5 mm, < 10 mm, or < 15 mm of induration. CONCLUSIONS: In controlling for false-negative PPD tests, the use of three skin test antigens, Candida, mumps, and tetanus, should provide reliable control for delayed-type hypersensitivity anergy.

Animals↗

PubMed1994

Glial cells of the oligodendrocyte lineage express both kainate- and AMPA-preferring subtypes of glutamate receptor.

mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed abundantly in the CNS, yet functional studies of neurons and glia from brain suggest selective expression of AMPA receptors. We now show that glial cells of the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for GluR6, GluR7, KA-1, and KA-2, rapidly desensitizing responses to AMPA, and mRNAs for GluR-B, -C, and -D. Analysis of glutamate receptor currents in single cells reveals two receptor populations with high and low affinity for kainate and different sensitivity for potentiation by concanavalin A and for block of desensitization by cyclothiazide. Our experiments describe the characterization of native kainate-preferring receptors in glia and reveal coexpression in single cells of functional AMPA- and kainate-preferring receptors.

Animals↗

PubMed1994

A case of recurrent typhoid fever in the United States: importance of the grandmother connection and the use of large restriction fragment pattern analysis of genomic DNA for strain comparison.

An 8-year old girl was infected for a second time with Salmonella typhi by contact with her grandmother, a known typhoid carrier. The S. typhi from both patient and grandmother had closely related genomic pulsed field gel electrophoresis patterns that differed from epidemiologically unrelated strains. The girl responded well to a 14-day course of oral trimethoprimsulfamethoxazole. The grandmother was treated successfully with a 28-day regimen of oral ciprofloxacin. Typhoid fever remains an endemic disease in the United States, largely because of recognized chronic stool carriers. Most of these carriers had typhoid in the preantibiotic era and remain potential sources of disease when they provide meals for others, not uncommonly grandchildren. The importance of this "grandmother" connection to endemic typhoid fever is reviewed, as is the potential use of pulsed field gel electrophoresis pattern analysis for comparison of strains of S. typhi.

Aged↗

PubMed1993

Initial clinical assessment of the comatose patient: cerebral malaria vs. meningitis.

One hundred twenty-one Liberian children were admitted in coma to the ELWA Hospital, Monrovia, Liberia. Admitting diagnoses, before lumbar puncture, were compared with discharge diagnoses. Ninety-four children were discharged with a final diagnosis of cerebral malaria and 27 with a diagnosis of meningitis. The admitting diagnosis was correct in 76.6% (72 of 94) of patients with cerebral malaria and 59.3% (16 of 27) of patients with meningitis. The cerebrospinal fluid leukocyte count was the single most significant factor in determining the correct diagnosis. Without the cerebrospinal fluid analysis, the discriminant accuracy (77%), i.e. definitive separation of the two illnesses, was comparable to the physician's admission diagnosis (73%). Other data contributing to the differential diagnosis of cerebral malaria and meningitis included the number of days of fever before admission, the presence or absence of nuchal rigidity, fontanelle fullness and peripheral blood malaria smear. Mortality rates for cerebral malaria and meningitis were 14.9 and 29.6%, respectively. These data suggest that physicians cannot reliably discriminate between cerebral malaria and meningitis without cerebrospinal fluid analysis.

Adolescent↗

PubMed1992

Photothrombotic lesions of the frontal cortex impair the performance of the delayed non-matching to position task by rats.

The effects of photochemically induced lesions of the frontal cortex on the short-term memory capacity of the rat have been investigated using the delayed non-matching to position task. Pretrained animals received lesions and were tested 4 days after surgery and twice per week for 3 weeks. The lesions produced a profound impairment of performance of this task which was still evident 3 weeks after surgery. Spontaneous locomotor activity was recorded 7 days after surgery and no difference was found between the control and lesion group. These effects indicated a generalized disruption of performance of this task in the absence of motor dysfunction. These results suggest that photothrombotic lesions of the frontal cortex can produce reliable, long-term behavioural deficits.

Animals↗

PubMed1992

Effect of cyclooxygenase inhibition on amphotericin B-induced lung injury in awake sheep.

Amphotericin therapy in humans has been reported to cause severe pulmonary dysfunction in some patients, and these abnormalities have been reproduced in unanesthetized sheep. To determine the role of cyclooxygenase products in this response, paired, random-order experiments in 11 sheep were done using the cyclooxygenase inhibitor ibuprofen. Ibuprofen blunted increases in pulmonary artery pressure (Ppa) after amphotericin (peak Ppa 38 +/- 3 cm H2O in amphotericin-alone group vs. 30 +/- 1 cm H2O in ibuprofen + amphotericin group, P less than .05) and reduced peak lung lymph flow to approximately 170% of baseline compared with 350% of baseline in amphotericin-alone group (P less than .05). In addition, the increase in airflow resistance across the lung and the decrease in partial pressure of oxygen seen after amphotericin was blocked by ibuprofen. Therefore, amphotericin-induced lung dysfunction is produced in part through the generation of cyclooxygenase products of arachidonic acid metabolism and can be ameliorated by pretreatment with the cyclooxygenase inhibitor ibuprofen.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Acute hemorrhagic conjunctivitis.

Acute hemorrhagic conjunctivitis, an infection caused by enterovirus 70 and a variant of coxsackievirus A24, is characterized by the rapid onset of severely painful conjunctivitis and subconjunctival hemorrhage. The condition is usually benign and resolves in five to seven days; however, a polio-like paralysis (radiculomyelitis) develops in approximately one in 10,000 patients infected with enterovirus 70. No treatment is available. Information about acute hemorrhagic conjunctivitis should be provided to patients and the community in order to prevent undue alarm, discourage home remedies and control the spread of this highly contagious disease.

Conjunctivitis, Acute Hemorrhagic↗

PubMed1990

A descriptive study of 42 cases of Branhamella catarrhalis pneumonia.

PURPOSE: We studied the clinical and laboratory findings of patients with pneumonia due to Moraxella (Branhamella) catarrhalis to better characterize the types of patients who develop this pneumonia, the clinical features of the illness, and the type of and response to drug therapy, as well as the immediate and long-term survival of these patients. PATIENTS AND METHODS: Patients with sputum samples that met cellular criteria as quality samples and that grew B. catarrhalis as the sole pathogen were identified retrospectively from microbiology records at a regional referral hospital for cardiac and pulmonary diseases. Records of these patients were reviewed to identify patients with radiographic findings of pneumonia. Clinical and laboratory characteristics of these patients were then studied in detail. RESULTS: Forty-two patients who met the criteria for B. catarrhalis pneumonia were identified. Most patients were elderly (over 65 years; 55 percent), malnourished (69 percent), and had severe chronic obstructive pulmonary disease or another serious underlying disease (98 percent). The seasonal incidence of this pneumonia was October through April (88 percent), with the annual number of cases having increased since 1982. The clinical presentation was typically mild. Interstitial or mixed interstitial-alveolar infiltrates superimposed on pre-existing chronic lung disease was the most common radiographic finding. Approximately 90 percent of sputa were acceptable for Gram stain and contained 10 to more than 50 gram-negative cocci/1,000 x field. All cultures produced a heavy growth of B. catarrhalis, with 67 percent of strains positive for beta-lactamase. No patient had identified bacteremia (zero of 25 tested). Therapy with numerous agents including cefotaxime, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole resulted in a good clinical and bacteriologic response. However, 45 percent of patients died of their underlying diseases on this admission or within three months. CONCLUSION: These findings provide a good profile of B. catarrhalis pneumonia. Despite the mild character of the illness, the pneumonia occurs in patients with end-stage pulmonary or malignant disease and almost 50 percent of patients die of their underlying diseases within three months.

Adult↗

PubMed1989

The effects of adenosine triphosphate and related purines on arterial resistance vessels in vitro and in vivo.

The distribution of P2-purinoceptors in pre-capillary resistance vessels was studied in vitro, using Krebs perfused rabbit ears and in vivo, in autoperfused hindquarters, intestinal and renal vasculatures of pentobarbitone anaesthetised cats. ATP (10(-10)-10(-6) mol i.a.) caused dose-dependent vasodilatation which, in the rabbit ear, was antagonised by reactive blue 2 (10(-5)-10(-4) M). At the highest concentration of reactive blue 2, ATP responses were reversed and a dose-dependent vasoconstriction was seen. Reactive blue 2, also reduced the vasodilator responses to carbachol and to a lesser extent papaverine which suggests that the antagonist has limited selectivity. The rank order of potency of ATP analogues as vasodilators, 2-methylthio ATP greater than ADP greater than ATP greater than alpha,beta-methylene and beta,gamma-methylene ATP, suggests P2y purinoceptors are involved. The selective P2x-purinoceptor agonist, alpha,beta-methylene ATP, caused pronounced vasoconstriction in the rabbit ear and cat intestinal vasculature which was not antagonised by phenoxybenzamine. In contrast, alpha,beta-methylene ATP had little effect in the autoperfused hindquarters and renal vasculatures suggesting a very heterogeneous distribution of P2x-purinoceptors in the cat. The results are consistent with the proposal that two distinct types of P2-purinoceptors are present on blood vessels.

Adenosine Triphosphate↗

PubMed1989

Branhamella catarrhalis infections.

Branhamella (Moraxella) catarrhalis is responsible for a significant number of bronchopulmonary infections in adults, as well as otitis media and sinusitis in children. This gram-negative diplococcus is indistinguishable from Neisseria gonorrhoeae on gram-stained smear. Many strains of the organism produce beta-lactamase and are resistant to the penicillins and other beta-lactam antibiotics. When B. catarrhalis is the probable pathogen, a beta-lactamase-resistant antibiotic is the initial drug of choice in both adults and children.

Adult↗

PubMed1989

Pneumonia due to Moraxella (Branhamella) catarrhalis.

Branhamella catarrhalis is a Neisseriae-like organism that is the newest member of the family of pneumonic pathogens. The organism is seasonal, encountered only during the respiratory disease season. The majority of patients with pneumonia (80% to 90%) have underlying chronic pulmonary disease, and their clinical illness may be difficult to distinguish from exacerbations of lung disease by other causes. B catarrhalis is the most common bacterial pathogen in this setting after Haemophilus influenzae and Streptococcus pneumoniae. The organism is easy to identify in the laboratory, with a quality gram stain of sputum being the key to recognition. Most patients show patchy non-cavitary infiltrates on chest roentgenograms. Because 75% of isolates produce beta lactamase, empiric therapy with penicillin or amoxicillin is likely to fail. Recommended drugs include erythromycin, trimethoprim/sulfamethoxazole, amoxicillin/clavulanic acid (Augmentin), or one of the newer broad spectrum cephalosporins.

Anti-Bacterial Agents↗

PubMed1987

Brucellosis.

Brucellosis is common worldwide in a variety of animals and is markedly underreported in man. Brucella abortus seems to be decreasing in cattle herds, but new animal reservoirs are being discovered. Human infection presents a difficult diagnostic challenge because of its protean manifestations and multiplicity of organ involvement. Symptoms vary, but fever, chills, weakness and weight loss are common. Several antibiotics are effective.

Animals↗

PubMed1986

Uniform chromatographic conditions for quantifying urinary catecholamines, metanephrines, vanillylmandelic acid, 5-hydroxyindoleacetic acid, by liquid chromatography, with electrochemical detection.

Uniform liquid-chromatographic conditions were developed such that we could quantify norepinephrine, epinephrine, normetanephrine, metanephrine, vanillylmandelic acid, and 5-hydroxyindoleacetic acid in urine by using a single mobile phase of monochloroacetic acid and citric acid, 0.1 mol/L each. All compounds were separated on a C18 column and detected electrochemically at a potential of +0.800 V. Optimization of these uniform chromatographic conditions significantly shortens the changeover time required from one assay to another, resulting in a substantial savings of time and cost to the laboratory.

Catecholamines↗